Pharmaceutical Compounding and Dispensing Pharmaceutical Compounding and Dispensing SECOND EDITION John F Marriott BSc, PhD, MRPharmS, FHEA Professor of Clinical Pharmacy Aston University School of Pharmacy, UK Keith A Wilson BSc, PhD, FRPharmS Head of School Aston University School of Pharmacy, UK Christopher A Langley BSc, PhD, MRPharmS, MRSC, FHEA Senior Lecturer in Pharmacy Practice Aston University School of Pharmacy, UK Dawn Belcher BPharm, MRPharmS, FHEA Teaching Fellow, Pharmacy Practice Aston University School of Pharmacy, UK Published by the Pharmaceutical Press 1 Lambeth High Street, London SE1 7JN, UK 1559 St Paul Avenue, Gurnee, IL 60031, USA Ó Pharmaceutical Press 2010 is a trade mark of Pharmaceutical Press Pharmaceutical Press is the publishing division of the Royal Pharmaceutical Society of Great Britain First edition published 2006 Second edition published 2010 Typeset by Thomson Digital, Noida, India Printed in Great Britain by TJ International, Padstow, Cornwall ISBN 978 0 85369 912 5 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, without the prior written permission of the copyright holder. The publisher makes no representation, express or implied, with regard to the accuracy of the information contained in this book and cannot accept any legal responsibility or liability for any errors or omissions that may be made. The right of John F Marriott, Keith A Wilson, Christopher A Langley and Dawn Belcher to be identified as the author of this work has been asserted by them in accordance with the Copyright, Designs and Patents Act, 1988. A catalogue record for this book is available from the British Library. Contents Preface ix About the authors x Acknowledgements xi Museum of the Royal Pharmaceutical Society xii British Society for the History of Pharmacy xiv Online material xv Part 1 History of compounding 1 1 Historical perspective 3 The origins of the pharmacy profession 3 Foundation of the Royal Pharmaceutical Society of Great Britain 5 Pharmacy legislation 6 Development of the pharmacopoeias 8 2 Obsolete dosage forms, equipment and methods of preparation 17 Obsolete pharmaceutical preparations and preparative methods 18 Old pharmaceutical equipment 34 Old pharmaceutical containers 38 3 Historical weights and measures 41 Metrication 41 Part 2 Pharmaceutical forms and their preparation 47 4 Key formulation skills 49 Weights and measures 49 Medication strength 59 5 Extemporaneous dispensing 65 Guide to general good practice requirements 65 Suitable record keeping 67 Equipment 67 Product formulae 74 Ingredients 75 Storage and labelling requirements 91 Pharmaceutical packaging 96 vi | Contents 6 Solutions 101 Introduction and overview 101 General principles of solution preparation 103 Oral solutions 104 Gargles and mouthwashes 105 Enemas and douches 105 External solutions 105 Worked examples 106 Summary of essential principles relating to solutions 112 7 Suspensions 115 Introduction and overview 115 General principles of suspension preparation 116 Oral diffusible suspensions 117 Oral indiffusible suspensions 119 Suspensions for external use 119 Worked examples 120 Summary of essential principles relating to suspensions 127 8 Emulsions 131 Introduction and overview 131 Formulation of emulsions 133 General method of preparation of an emulsion using the dry gum method 135 Stability of emulsions 136 Emulsions for external use 137 Worked examples 138 Summary of essential principles relating to emulsions 151 9 Creams 153 Introduction and overview 153 Terminology used in the preparation of creams. pastes and gels 181 11 Suppositories and pessaries 183 Introduction and overview 183 General principles of suppository and pessary preparation 184 General method for suppository preparation 186 Worked examples 187 Summary of essential principles relating to suppositories and pessaries 192 . pastes and gels 153 General principles of cream preparation 154 Worked examples 156 Summary of essential principles relating to creams 160 10 Ointments. pastes and gels 163 Introduction and overview 163 Ointments 163 Pastes 165 Gels 167 Worked examples 170 Summary of essential principles relating to ointments. ointments. lotions and applications 249 18 Ointments and pastes 253 19 Powders 257 20 Miscellaneous formulae 259 Appendix 1 Glossary of terms used in formulations 261 Appendix 2 Abbreviations commonly used in pharmacy 263 Appendix 3 Changing substance names from British Approved Names to recommended International Non-Proprietary Names 265 Bibliography 271 Index 273 . Contents | vii 12 Powders and capsules 195 Introduction and overview 195 Bulk powders for external use 195 Bulk oral powders 196 Individual unit dose powders 197 Unit dose capsules 199 Worked examples 202 Summary of essential principles relating to powders and capsules 205 13 Specialised formulation issues 207 Introduction and overview 207 Posology 207 Dermatological extemporaneous formulation 213 Further reading 215 Part 3 Product formulae 217 Preface 219 14 Creams 225 15 Dusting powders 229 16 Internal mixtures 231 17 Liniments. . to familiarise themselves with the compounding tech- tical practitioner to compound medicines in a local niques necessary to produce products of appropriate pharmacy environment. this work is intended January 2010 . In addition. Primarily. First. accrued and refined. we hope that should the need cultural or local emergency. of the historical pathways that have led to the present technological position of pharmacists. The text also has a role when considering the ries. the text is supported debate. albeit practitioners of pharmacy to be compounding medi- possibly in the face of some form of environmental. icines when conventional supply chains are either This second edition has updated the first edition unavailable or have broken down. John F Marriott unless many of the antiquated measuring systems. In addition.Preface Pharmacists or their pharmaceutical equivalents have as a reference-based tutorial to the methods employed been responsible for compounding medicines for cen. nature that might be encountered. the text now This text has been designed with a number of func. United Kingdom historian. Recently this role has been challenged in the to allow students and practitioners to be able to exam- pharmaceutical literature with suggestions and recom. cines on a daily basis. cedures (SOPs) pertinent to certain sectors of profes- mately lost. it is not beyond the bounds of sional practice today. it is clear that a vast array of skills and knowl. certainly over the last two centu. In the present environment it is possible that this design and implementation of standard operating pro- knowledge and skill base might be dispersed and ulti. However. in medicines’ compounding. and. they might be lost forever. to assist the student compounder. Although we do not expect all imagination to conceive that there will be times. The text has been designed turies. includes examples of the pharmaceutical label for each tions in mind. Notwithstanding this valid quality and efficacy. Keith A Wilson methodologies and formulations are preserved in Christopher A Langley some reference work. it is important to be aware of some worked example. or Dawn Belcher at least be totally unavailable except to the dogged Birmingham. however. when pharmacists might arise this text will effectively support any work of this be called upon to extemporaneously compound med. by moving images in order to augment the necessary edge with regard to medicines’ compounding has been techniques and expertise. ine either all or part of the subsequent chapters in order mendations that it is inappropriate for the pharmaceu. where she is employed as a pre-registration training at St Peter’s Hospital in relief manager. project themes revolve around the PK/PD of paediatric drug use and formulation. His research interests predominantly surround He has a proactive role in teaching in the depart. Current waste medication. principally in the areas of clinical pharmacy/ behind and possible solutions to the generation of pharmacology and medicines management. holding a variety of positions. Dawn Belcher is a qualified pharmacist who graduated from the Welsh School of Pharmacy in 1977 and then Keith A Wilson undertook her pre-registration training with Boots the Keith A Wilson graduated in pharmacy from Aston Chemist at their Wolverhampton store. After regis- University in 1971.About the authors John F Marriott Chertsey. registered in the UK for University to undertake a PhD within the Medicinal the last 25 years. tice of pharmacy and particularly in public policy and While raising a family she undertook locum duties for pharmacy services and pharmacy education. In addition he has wide. He is currently employed as Chief Pharmacist at the Royal Wolverhampton as a Senior Lecturer in Pharmacy Practice. where he degree programme. He is now Professor of Pharmacy tration she worked as a relief manager and later as a at Aston University with research interests in the prac- pharmacy manager for Boots the Chemist until 1984. She now enjoys teaching practical aspects of Chris Langley is a qualified pharmacist who graduated pharmacy practice while still keeping an association from Aston University in 1996 and then undertook his with Lloydspharmacy. pharmacy education but he is also involved in research ment and is working on the development of electronic examining the role of the pharmacist in both primary methodologies to support pharmacy learning and and secondary care. which continued until she took a permanent post in Christopher A Langley 2001. took over as the Head of the Pharmacy School in 2005. He has Boots the Chemist and in 1986 became an independent over 30 years’ experience in teaching on pharmacy locum working for a small chain of pharmacies in the undergraduate and postgraduate programmes and is West Midlands while also working for Lloyds a subject reviewer for the QAA in pharmacy and phar- Chemist. This includes examining the teaching. latterly time to pharmacy practice. In 1989 she began sessional teaching with macology and a member of the RPSGB accreditation the pharmacy practice group at Aston University panel since 1999. He practised in both community and Chemistry Research Group before moving over full hospital sectors. Upon registration. before joining the academic in teaching the professional and legal aspects of the pharmacy department at Aston University. control of antibiotic pre. he returned to Aston John Marriott is a pharmacist. Dawn Belcher scribing and medicines wastage. active research pharmacist’s role in public health and the reasons interests. specialising Hospitals NHS Trust. . pieces during the assembly of the still images and pounding knowledge during the preparation of Part 2 for the assistance offered by Briony Hudson (Keeper of the book. the authors are also grateful to Mike (Honorary Secretary of the British Society for the Turner who offered advice and the use of his equip. images. the authors are also very grateful to the them during the preparation of this book. of the Museum Collections) and Peter Homan In addition.Acknowledgements The authors are grateful to everyone who assisted Finally. Museum of the Royal Pharmaceutical Society of Special thanks are given to Edward Belcher for Great Britain for allowing access to various museum offering his advice and extensive pharmaceutical com. . History of Pharmacy) during the collection of the ment during the preparation of the video images. rpsgb.org/museum Medicine bottles dating from the seventeenth and eighteenth centuries. Books. services based on its collections.org www. labelled O:VULPIN. Museum of the Royal Pharmaceutical Society 1 Lambeth High Street London SE1 7JN UK. and also research of from traditional dispensing equipment to ‘Lambeth pharmacists’ family histories and the history of pre- delftware’ drug storage jars. The Museum has a large photographic archive medicines to medical caricatures. Delftware storage jar. excavated in the City of London in the 1950s. oil of fox. and from proprietary mises. the Museum offers historical research then cover all aspects of British pharmacy history. . Tel: þ44(0)20 7572 2210 museum@rpsgb. The 45 000 items collected since ters building. greetings cards and other merchandise based on the Museum’s collections are available directly from the Society and by mail order. and can supply images for reproduction. post- cards.Museum of the Royal Pharmaceutical Society The Royal Pharmaceutical Society has had a museum In addition to displays in the Society’s headquar- collection since 1842. believed to have been commissioned by Michael Hastings of Dublin in 1684. probably nineteenth century. . Nineteenth century medicine and poison bottles. Brass mortar and pestle. Museum of the Royal Pharmaceutical Society | xiii Selection of medicines containing opium. Group of objects from the collection of the Museum of the Royal Pharmaceutical Society. measures and a cork press. UK.org. Tel: þ44(0)116 2640083 bshp@associationhq. having originated from a committee contact: of the Royal Pharmaceutical Society. from the works of the ancient apothe- Thurmaston cary to today’s ever changing role of the community. Leicester LE4 8BN wholesale or industrial pharmacist.uk . It seeks to act as The British Society for the History of Pharmacy a focus for the development of all areas of the history 840 Melton Road of pharmacy. formed in 1967.British Society for the History of Pharmacy The British Society for the History of Pharmacy was For further details about membership and events. 7 seconds) 7 Dispensing Powders (9 minutes. 17 seconds) . 5 seconds) 1 Dispensing Solutions (5 minutes. 11 seconds) on www. 6 seconds) 6 Dispensing Suppositories (6 minutes.com/PCD videos. 13 seconds) enter the access code PCD2edOV. 5 Dispensing Ointments (8 minutes.pharmpress. Please 4 Dispensing Creams (5 minutes.Online material The following is a list of the videos available 3 Dispensing Emulsions (4 minutes. 35 seconds) 2 Dispensing Suspensions (8 minutes. . PART 1 History of compounding . . vegetable and remedies and the weights and measures used. Egyptian society was supported between approximately 1250 BC and 285 BC. but it Written works on papyrus have also been discovered is known that the compounding of medicinal prepara. rice. used by the Assyrians. such as opium. Examples It is impossible to determine when humans first began of medicines’ chests containing dried drugs and the to mix substances and concoct preparations that pro. Greece. with the Egyptian cultures. and indeed of Ancient Egypt. appear that the Ancient Greek medical practice used . are still used today. Rome and the Arabian cul. all developed complex levels of Prepared drugs were also a feature of the various medical knowledge. integrating various aspects of Mesopotamian civilisations that existed in parallel pharmacy and medicines compounding. formulae. Many mineral sources has been practised in a sophisticated of the vegetable-based drugs. that describe contemporary materia medica. for example. some remain in current use. The societies minerals described are recognisable today. throughout this period of diverse tributions to medicine and pharmacy principally cultural development. Again. It would by specialist medical and pharmaceutical practice. myrrh and liquo- ence upon social and scientific development through. animal products and form by a range of ancient civilisations. some of the drugs The Ancient Egyptian cultures exerted an influ. out the period extending from approximately 3000 BC The Ancient Greek civilisations made known con- to 1200 BC. Clearly. tools associated with compounding have been found. tions from materia medica of animal.1 Historical perspective The origins of the pharmacy profession 3 Subsequent London Pharmacopoeias 9 Foundation of the Royal Pharmaceutical Society The Edinburgh Pharmacopoeias 11 of Great Britain 5 The Dublin Pharmacopoeia (Pharmacopoeia Pharmacy legislation 6 Collegii Medicorum Regis et Reginae in Hibernia) 12 Important legislation since 1850 6 Unofficial reference works 12 Development of the pharmacopoeias 8 The British Pharmacopoeia (BP) 13 The first recognised pharmacopoeia? 8 The British Pharmaceutical Codex (BPC) 15 The first London Pharmacopoeia The International Pharmacopoeia (World (Pharmacopoeia Londinensis) 1618 8 Health Organization) 15 The origins of the pharmacy Archaeological research shows widespread evidence of medicines compounding being central to the thera- profession peutics practised by the Ancient Egyptians. duced either perceived or real therapeutic effects. tures. Hippocrates also emphasised including those by John Mesu€e Senior (d. of these principles was begun by employing a more medicines and compounding. but compound.4 | History of compounding fewer drug-based therapies than the Egyptian and Many important texts containing information on Mesopotamian cultures. which spread from areas medicine had risen. 980–1036) necessity for absolute cleanliness in surgery. Prior to this period Roman medical previously unused medicinal agents were described and pharmaceutical practice had revolved around reli. Each of these great practitioners tional medical works were resurrected and refinement left written works containing information on drugs. betel nut. apothecaries translated many of the ear- entered the Dark Ages and medical and pharmaceuti. principally conducted preparation. lier Arabic pharmaceutical works into Latin. By contrast. As a cal practice was transformed into a ‘monastic’-driven result of these activities. 970). Typical of that are still causing problems in the treatment of the texts of the period and area is the Corpus of patients today. under the influence of imported developed and disseminated along Graeco-Arabian Greek practice. which After the disintegration of the Ancient Greek civ. where close contact had Empire a substantial number of influential practi. the medieval period and the spicers began to evolve . In the thirteenth-century German court of As the Roman Empire disintegrated. been established with Arabian invaders. cepts in medical and pharmaceutical practice were By around 30 BC. the origins of the pharmaceutical pro- beliefs. compiled by Ibn al Baitar of Malaga. much of the classical literature throughout the Dark and Middle Ages. Simples. Drugs and prepared East. some evidence to show that at least 300 Roman Empire. Many of these new agents appear to have by the lower sections of society such as slaves (servi arisen from introductions by the Arabs from the Far medici) and wise-women (sagae). tioners were in evidence. including Celsus. moved either to Rome or to other parts of the however. tradi- corides and Galen. Frederick II system. in the Eastern Byzantine area of fession arose principally from trading arrangements the Roman Empire. largely contains information on drugs and compound- ilisation around 220 BC. Despite this. drug pedlars (pharmacopoloe) and those emerge from the post-Roman Dark Ages. Abu the importance of pure water in medicine and the Mansur (c. In centres of learning throughout Europe. centred on Constantinople. which formed the basis scientific approach to medicine. nux medicines were used by the Romans. Dark Ages. many Greek physicians ing originating from older classical works. vomica and the widespread use of cane sugar as a ing again appeared to be chiefly carried out by less component of formulations. These merchant period also derived information from their studies on bodies were among those who formed Guilds during alchemy. rhubarb. the West Frederick II. around 400 drugs and compounding were compiled by the great drugs are described by Hippocrates. around 1240. with herb-gatherers By the eleventh century. Ibn Sina (Avicenna. Traditional Graeco-Roman medical texts The dealing in medicines and materia medica fell were translated into Arabic and compiled with other under the trades of ‘mercery’ and ‘spicery’. Europe was beginning to (rhizotomi). the status of some of those practising lines of communication. the latter works collected from the Far East. practice as an entity distinct from other professions. There is. During this time. by the key Arabic texts dealing with pharmaceutical gious and superstitious ritual. and until the fall of the Roman around the Mediterranean. New con- trading in salves (unguentarii) being in evidence. Close links on therapeutics and drug trading links was retained. The Arabs of this being traded by spicers and pepperers. c. which that had begun in Roman times and continued remained until 1453. was largely based upon religious and superstitious In England. 425 BC. 857). had been formed with continental Europe. Dios. Interestingly. prominent sections of society. issued an edict that defined the role of pharmacists Roman therapeutic principles were preserved. and include cloves. writing around Arab physicians of the seventh to thirteenth centuries. particularly An additional eastern repository and incubator of France following the Norman invasion and the subse- medical knowledge developed in Arabia during the quent Crusades. features and Ibn al Baitar of Malaga (1197–1248). although some Graeco. of therapeutics well into the seventeenth century. ities in procuring. Mr Benjamin Hawes to amend the laws relating to the quently ratified an extensive apprenticeship system medical profession of Great Britain and Ireland. It is from this group that resulted in the finding that apothecaries could give the specialist apothecary arose. following the achievement of one of were able to pay for consultations and treatments. they nineteenth century there were such large numbers of were also involved with providing medical advice. however. made responsible for education and registration of apothecaries. would be unaffected by the legislation. under which the Society of Apothecaries was the Bishop of London or the Dean of Saint Paul’s. formed in 1802. would have been regarded as practis- progressed through the courts. The Asso- Physicians was relatively small (around 100) and they ciation of Chemists and Druggists was reconfigured generally concentrated on the treatment of wealthy and expanded to form the General Association of patients. This was soon dis- At this time. a reversal of the previous Pharmaceutical Society of Great situation. advice to patients and prescribe medication in addition By the fifteenth century the apothecaries were to compounding and selling medicines. Chemists and Druggists in 1829. The Society of In 1841 a Bill was introduced to the Commons by Apothecaries had been founded in 1617 and subse. formance requirements on them. concession in the Apothecaries Act was due. A subsequent court decision made in 1829 ruled that apothecaries could make charges for Foundation of the Royal their professional advice. in part. though they highly specialised in the art and practice of pharmacy. . such as recommending therapies or treating edly practising medicine without a licence. since any activities involving William Rose was prosecuted by the College for alleg. disagreements with the physicians began to emerge. by the not only compounding and dispensing medicines. culminating in an ing medicine. The impact of the pro- College of Physicians and the Society of Apothe. compounding and selling drugs cians. posed legislation on chemists and druggists would caries regarding the authority to prescribe medicines have been to require them to be regulated by exami- erupted in the ‘Rose case’. This Act ef- tion to their respective rights to practise pharmacy and fectively enabled chemists and druggists to practise to provide medical advice. notably the removal of duty This group most often sought advice and help from levied on certain compounded medicines. Despite the controlled existence of the College of This conflict arose primarily because apothecaries were Physicians and the Society of Apothecaries. During the eighteenth and early nineteenth centu. The final outcome compounding of medicines. Bill intended to effect a drastic reorganisation of the In 1703 a long-standing dispute between the way medicine was practised. Historical perspective | 5 into a body concentrating upon the manipulation and appeal in the House of Lords. Britain The Apothecaries Act (1815) also clarified the sta- tus of chemists and druggists. stating that their activ- For centuries disputes had occurred between physi. to the concerted lobby presented by the Association ries the number of Members of the Royal College of of Chemists and Druggists. in which apothecary nation before practising. the aims of the group. chemists and druggists to secure such an important maceutical practitioners. however. This case minor ailments. patients. apothecaries and chemists and druggists in rela. The ability of the islation which placed controls upon medical and phar. Eventually the Apothecaries Act was passed in that practitioners had to be examined and ratified by 1815. This for members. These disputes led to the pharmacy without imposing any educational or per- introduction of a number of keynote elements of leg. either unqualified or poorly qualified individuals Physicians protected their status by petitioning the practising that it became apparent that legal reform crown and Henry VIII issued a regulation that restricted of the education and registration procedures was nec- the practice of medicine to physicians by stipulating essary. apothecaries and surgeon-apothecaries. could only seek remuneration for any activity involv- and it was during this period that the long-standing ing the supply of medicines. a large middle class existed who banded. with some pro bono work among the poor. Moreover. that many of their body year the Society petitioned for a Royal Charter. and uniformity of products available. Naturally these restrictions had a major ‘The Pharmaceutical Society of Great Britain’ and a impact on the nature of products that could be legally formal report was then sent to over 5000 prospective compounded and sold. In November of that were cognisant. rules were drafted and approved and a The control of poisons was further extended in aspects temporary committee agreed until the general meeting of the Pharmacy Act 1908. and ‘druggist’ were restricted under this Act. Through these such individuals operated the business of selling med- efforts and those of other professionals the Hawes icines. with obvious outcomes in terms of the quality Bill was withdrawn. members. chemists and drug- to warrant further meetings to develop the formation gists and apprentices or students. oping a ‘Poisons List’. The campaign to enable the education and regis- tration of chemists and druggists was not forgotten. thereby restricting the title tige of pharmacists. although it did not restrict The initial meeting to promote this concept was the use of ‘chemist’ or ‘druggist’ as titles. The titles ‘chemist’ of the proposed new society. A subsequent meeting. however. medicinal products the Hawes Bill. was held in the Crown introduced restrictions on the sale of poisons by devel- and Anchor Tavern in the Strand on 15 April 1841. It also chaired by William Allen FRS. itous under the terms of the Apothecaries Act (1815) in being able to practise effectively without regula- tion. ‘pharmaceutical chemist’. membership certificates. the proficiency of prospective pharmacists and to issue bership and ultimately enhancing the status and pres. Savory. At the inaugural meeting of the new Society. The proposed society was intended to ning the original aims embodied by the formation of serve a number of functions. Items from this list could only be During this meeting a resolution was adopted to sold by pharmaceutical chemists and by chemists and form an association of chemists and druggists called druggists. Moore and Co and John Bell and Co.6 | History of compounding Chemists and druggists. held at Bell’s house and has been referred to subse- The Pharmacy Act 1868 quently as ‘the pharmaceutical tea-party’. Under this legislation the unified front in promoting and protecting the interests Pharmaceutical Society was empowered to examine of pharmacists. supported by a written petition sport. could be sold by any individual who was at liberty to ing over 600 signatures from chemists and druggists use the title ‘pharmaceutical chemist’. including representatives from Allen. in that the list of poisons . Before the 1850s. There This extended the scope of the 1852 Act to require the were sufficient numbers of chemists and druggists Registrar of the Pharmaceutical Society to keep regis- motivated by the recent dealings of the Hawes Bill ters of pharmaceutical chemists. developing the education of the mem. held Poisons and Pharmacy Act 1908 on 1 June 1841. Important legislation since 1850 however. was granted on 18 February 1843. relevant legislation that has influenced the manner in The outcome of this meeting was that vociferous which pharmaceutical compounding has been con- representations were made to Parliament opposing ducted in the UK. which were poorly educated and that they had been fortu. Jacob Bell believed that the solution to this problem resided in the formation of a unified society The Pharmacy Act 1852 formed from the chemists and druggists practising in This Act provided the legislative framework underpin- Great Britain. particularly those from planned for May 1842. there all opposed to any moves to remove their right to were no formal controls on the premises from which prescribe and recommend medicines. principally to present a the Pharmaceutical Society. Meetings were held in February 1841 at which Pharmacy legislation the main wholesalers were greatly in evidence. By the end of 1841 around 800 London. began to form an opposition strategy to the members had joined the Society and in 1842 the mem- proposed Bill. Some of these established practitioners bership had increased to 2000. Hanburys and It is useful to consider the historical development of Barry. with few exceptions such (1939) prohibited the advertising of treatment for neo- as emergencies and in very remote areas. This list contained agents such as vaccines maceutical chemists was established. tered under this Act. All pharmacy premises were regis- the compounding process. which also dictated that all registered pharmacists must be members of the National Insurance Act 1911 Pharmaceutical Society. through Glyn-Jones. In 1917 the Venereal Diseases was that pharmacist contractors became the almost Act made the advertising of remedies for venereal dis- exclusive compounders and dispensers for prescrip- eases illegal in the same way that the later Cancer Act tions under the legislation. original estimates of costs were not viable. hospitals. Committee as a disciplinary body and the pharmaceu- ness of a chemist and druggist. and control of both the manufacture and the sale . In addition. National Insurance Act 1946 The Health Ministries in the UK became responsible Ministry of Health Act 1919 for the general practitioner and pharmaceutical ser- This Act created the Ministry of Health and trans. All those listed in and sera and was extended later. supplies. The National Insurance Act of 1911 was passed The Pharmacy and Poisons Act (1933) also established at the time that the Secretary of the Pharmaceutical the Poisons Board. mental health and local authority ser- ferred responsibilities for health from other bodies vices. Historical perspective | 7 was expanded. Therapeutic Substances Act 1925 Pharmacy Acts 1953 and 1954 This Act controlled the licence to manufacture a stated Under this legislation the register of chemists and list of products that could not be tested by chemical druggists was abandoned and a new register of phar- methods. state. ensured that pharmacists were This Act further defined the nature of premises in the principal dispensers and compounders of medi- which medicines could be sold. version. vices. These Acts were the precursors of the advent of evidence-based pharmacotherapy. reversing professionals could develop the dispensing element of the situation that existed under the Medicine Stamp their businesses. which was created to advise the Society of Great Britain. restricting such sales to cines for those patients prescribed medication in shops rather than temporary structures such as stalls accordance with this Act. Pharmacy and Poisons Act 1933 Therapeutic Substances Act 1956 Under this legislation the Pharmaceutical Society was Previous legislation was rationalised under this Act charged with ensuring compliance with the Act. Not surprisingly. sewage). One of the outcomes of this Act ‘patent’ medicines. plastic disease. the Poisons List. which exempted the need to show the led to the pharmacist contractors being requested to composition of these medicines if an appropriate duty ‘discount’ their activities when it became apparent that had been paid. notably when greater the abolished registers were incorporated into the new numbers of antibiotics were introduced. was a Secretary of State with respect to the composition of Member of Parliament. The need to indicate the composition of the beginning of the process whereby pharmaceutical proprietary medicines was also established. Accordingly this established and barrows. this Act laid out the terms leading to the development of both the Statutory under which a body corporate could conduct the busi. this legislation also Act (1812). National Health Services Act 1946 Venereal Disease Act 1917 This legislation led to the development of an all- For a number of years both the medical and pharma- embracing Health Service. These measures clearly had The pharmaceutical profession has been intimately great bearing upon the pharmaceutical environments involved with the movements to establish a welfare in which compounding operations were conducted. William Glyn-Jones. thus further controlling tical inspectorate. together with aspects of public health (water which were further developed in later legislation. The influence of the Society. including the availability ceutical professions had called for controls to be of pharmaceutical services which extended to the placed upon the unsubstantiated advertisement of whole population. but it by Jerome Brunschweig. and specific physicians. along with other similar works such School of Salerno. Many elements from it sources. This concept presumably arose from posi- Inevitably. The former work listed develop a text under the stewardship of 24 illustrious simples according to their qualities. This contained many old but most of the early pharmaceutical texts only formulae derived from traditional sources. Arabian medicine in both the East and the West. The In the Dispensatorium the herbs. texts such as the Recettario fiorentino (which was Two particular examples of sixteenth-century established in Florence in 1498 and then used widely pharmaceutical texts applied widely across Europe throughout Italy) itself based upon the Antidotarium were Chirurgerye by John Vigon. but also con- One of the earliest formally developed and widely tained a number of unique references to medicines. which were intended to be ence source for physicians and apothecaries in implemented in certain specified towns and districts. which was 1076 to around 1224 when it began to decline in influ- itself sourced from the first herbal compiled in French. which appeared in of Nicolaus Myrepsius. accepted compilations of medicines’ compounding was including the first accurate description of nux vomica the Antidotarium Nicolai of Nicolaus Salernitanus and many preparations of essential oils. macopoeia of the Middle Ages. including confections. 1100). which contained 139 complex pre- Dispensatorium of Valerius Cordus was adopted by scriptions in alphabetical order in conjunction with the Senate of Nuremberg. and the Most Excellent Homish Apothecary pharmacopoeia was debated by the College. including exerted a local influence on medicines’ usage. which was a thirteenth- England in a translation by Bartholomew Traheron century work. which was produced in an was not until 1589 that it was decided formally to English translation (1561). preparation and uses. together with some were in use long after the thirteenth century. Avicenna. The latter text contained many remedies. an English translation of Le lowing the conquest of Salerno by the Normans in Grant Herbier en Francoys (1516–1520). pharmacopoeia that would act as a standard refer- copoeias were developed. At this time throughout eficial to develop some form of national formulary or Europe a number of city-based or municipal pharma. Indeed. Mesu€e and Rhazes. spiced fruits and pills. Development of the pharmacopoeias The first recognised pharmacopoeia? Perhaps the first widely recognised pharmacopoeia Formularies and pharmacopoeias have been in use for was the Dispensatorium of Valerius Cordus (1515– almost as long as medicines have been compounded. was made the official pharmacopoeia in Naples and Sicily by Ferdinand II in the early sixteenth century and a number of preparations current in the twentieth cen. pilles and confections’. the texts was generally an ad hoc affair until the early part College of Physicians indicated that it would be ben- of the sixteenth century. minerals and Antidotarium Nicolai was compiled at this institution other crude drugs were arranged in alphabetical order and became probably the most widely accepted phar- and information was given about their identification. oyles. some of these works became more widely tive experiences of the early College founders with recognised. In June 1585 the concept of a standard (1543). This period equates to the peak influence of Arbolayre (c. cerates. 1544) (first edition 1546). which was particularly active fol- as The Grete Herball. sters. ence. England. it detail of pathology and therapeutics. Galen. It was well known in England in the six- Salernitanus was the superintendent of the Medical teenth century. spices.8 | History of compounding and supply of agents listed as therapeutic substances formulae were given for ‘oyntmentes. The first London Pharmacopoeia tury can be traced to it. 1485). Nicolaus copoeia’. The (from c. (Pharmacopoeia Londinensis) 1618 Uptake and official recognition of pharmaceutical Within a few years of its foundation in 1518. These physicians were charged with . pilay- was combined in this single piece of legislation. which gave rise to the work monographs and references to simples (drugs) and being known later as the ‘Nuremberg Pharma- pharmaceutical preparations (electuaries). The Pharmacopoeia was finally published ing various materia medica of animal origin. Syrups. was made up of over 130 com- no pharmaceutical personnel were involved directly. lozenges. waters. Never- in April 1618 directing all apothecaries to use this text theless. many of which mercury salts. Pharmacopoeia contained a huge number of ingredi- ents. in their practice. pills. tions. of which over half were of plant origin (roots. For example Confectio de Hyacinthi con. The Pharmacopoeia contained The manuscript was ready for publication in 1617 a large number of items and preparations that had following a lengthy period of examination by expert been derived from older and even ancient texts. vegetable and mineral origin were also today. includ- physicians. animal and herbal sources that were . indexed document. including on 7 May 1618 following a Royal proclamation issued desiccated whole animals and excrements.g. Waters. conserves. Tragematae. newer chemical therapies were also included. For together with a larger number of chemical entities example. Sir Theodore de number of simples included had been expanded from Mayerne. lard and powdered lead. the 1618 ‘Official’ Pharmacopoeia con- (Medicamenta Chymicae Praeparata). plasters. Since the ‘official’ December 1618 Pharma. which was used against compounds. 1632 and 1639. it can only be assumed that disagreement within the College of Physicians had led to the re-evaluation Subsequent London Pharmacopoeias of the list of recommended products. powders. poison and plague. conserves. who had a particular interest in experimen- 680 to 1190. which would be year by the first ‘official’ edition. syrups. The introduction of in May. Strangely. This edition was dedicated to Charles II and contained tained in excess of 50 ingredients and the Great most of the simples and therapeutic preparations from Antidote of Matthiolus. in an apothecary’s premises for their production. spirits. such as the tained around 178 simple waters. Mercurius Dulcis Pharmacopoeia was replaced in December of the same (calomel) and some iron preparations. powders. lini- lished under the auspices of the Commonwealth and ments. herbs. simples. as were the number of complex prepara. tinctures. though it was indicated that appropriate advice from It is clear that a high level of pharmaceutical exper- pharmacists should be sought when compiling any tise was required to compound these treatments. Other less well- previous editions. oils. which only applied to England. preparations requiring expert technical manipulation ointments. tures). decoctions. this first edition of the for example various mineral acids. included. tal pharmacy. ponents. unguents. oils. a six-page section still would require distillation (or evaporation) in their included a miscellany of bizarre substances clearly production. pub- nised today. The 1618 London Pharmacopoeia was revised in sub- The Pharmacopoeia contained a large number of sequent versions in 1621. Historical perspective | 9 detailing the preparations to be included. plasters and salts were all represented. expected to produce positive therapeutic outcomes if tially revised and expanded version of that published used in appropriate conditions. including pre- Many of the compound preparations in the pared worms and millipedes. The compound preparations The 1650 edition of the London were collected under headings that are largely recog- Pharmacopoeia (second edition) This edition was a 212-page. Significant quantities of materia medica of the form of which would be readily recognisable animal. Significantly. thought to be of pharmaceutical use. and certain products (Pharmacopoeia Collegii Regalis Londini) took the compound formulation approach to the (third edition) extreme. vinegars. which was a substan. Notably. these newer therapies appears to be the result of the copoeia contained a greater number of pages and the actions of the King’s physician. which refer to sugar and spice mix- ings of simples and a range of compound preparations. Most of these were included as compound decoctions. leaves and seeds). salts. little therapeutic value. but details of the methods of preparation and dosages paradoxically many of the preparations would be of to be recommended. The recognised groups of medicaments were also included 1650 Pharmacopoeia was also arranged under head- (e. was obviously intended to have wider influence than chemicals and metals all appeared. It was common to find preparations with The London Pharmacopoeia 1677 between 10 and 30 components. which was an expanded tury. Olea per Infusionem et this edition of the London Pharmacopoeia and its . gold. synonymis and Quid pro quo on substitutes (Simon Despite the obvious attempts to modernise this edi- Januensis. The 1677 edition Decoctionem 134. Cerata 150. 936– However. Two editions of the latter work were included in the 1746 edition would have been recog- referred to: the first Nicolaus Parvus (common edi- nisable and in common use in the early twentieth cen- tion) and Nicolaus Magnus. the details outlined in this Pharma- 1013).g. the text was still written largely in Latin. adoption of chemical medicines. the Gresham Professor of Physic. Emplastra 136. plants in addition to even more chemical entities. A number of Sales et Salina 40. 1555) and the older. Vina 82. who donated land for the Chelsea This premise can be exemplified by the following list Physic Garden. cobalt. the Antidotarium of despite working only with observational evidence. Decocta et Infusa ples of alkaloids. Categories for metals (e. the Dis- ducts geared to containing only active ingredients. grouping can be derived by looking at the contents list and noting the number of pages devoted to each sec. edition) were as follows: Pondera et Mensurae 1. Extracta et Resina 31. Pemberton indicated that two classical works on The London Pharmacopoeia 1746 (fifth edition) simples by Avicenna (AD 980–1037) and Serapion This edition contained many important revisions and a (200–150 BC) should be consulted. Johannes Damascenus (or Mesu€e. the classes of preparations alphabetically. Also recommended was tion. Unguenta et began to address the need to categorise the increasing Linimenta 142. Praeparationes Simpliciores 22. Mixturae 96. efficacious pro- ing galenicals in current pharmacopoeias. tive table for chemical affinities in 1775. It is not surprising. with first section page number. (Bergmann was an 75. which presented galenical compounds arranged With a few exceptions. Succi 30. (1660–1753). Pilulae 118. which were striving to change their therapeutic practice was arranged in classes rather like the sections detail- towards treatment with less intricate. there was an active movement away from the Dessenius Chronenburgius (Lyon. number of inorganic chemical entities used therapeu- Apothecaries' recommended books (Henry tically.g. Liber Servitoris of Bulchasim (Ben Aberazerin. Mella et Oxymelita 105. d. The relative importance of each product version containing more preparations.g. 857). metal- Pemberton 1746) lis affinia (e. classical pharmaceutical sources and those Contributors to this work included Sir Hans Sloane originating from more modern trends and discoveries. plants and animal materials. Resinosa et Sulphurea 53. therefore. Aquae Stillatitiae Simplices 65. silver). The London Pharmacopoeia 1788 (sixth tion. Tincturae Spirituosae 86. including several exam- Stillatitiae Spiritosae et Spiritus 69. Electaria 122. Epithemata 152. it is clear that from the six- This edition also gave specific details concerning teenth to the eighteenth centuries those involved with weights and measures.10 | History of compounding included in the previous edition.) Trochisci et Tabellae 115. Pulveres 108. was introduced. cinnabar) and recrement Despite the development and promotion of official metallica nativa (e. pensatory (De compositione) of Dessen–Bernardus Thus. which examined the preparation of minerals. mercury. copoeia indicated that contemporary physicians. Torbern Bergmann’s names for chemical salts were Metallica 55. bismuth) were included. The contents. compounding relied in their professional lives upon a The London Pharmacopoeia 1721 (fourth range of texts that detailed therapies arising from both edition) traditional. Olea per Distillationem 36. Materia This edition of the London Pharmacopoeia signalled Medica 3. Olea ancient multicomponent preparations to the wider per Expressionem 35. thirteenth century). elaborate complex preparations. eighteenth-century chemist who produced the defini- Syrupi 98. that this of texts for the practising apothecary recommended in edition included accurate botanical descriptions of the mid eighteenth century by Dr Henry Pemberton. There was also a physical difference between Aquae Medicamentosae 132. together with De large number of obsolete preparations were removed. Aquae used and a range of new drugs. pharmaceutical works. Condita 29. tury). Conservae the movement from the recommendation and use of 27. This edition Antidotarium of Nicolaus de Salerno (twelfth cen- was said to excel in Galenic pharmacy. Pharmacopoeia in terms of advances in chemical anal- copoeia was stressed. was produced following the appointment of a Phar- The London Pharmacopoeia 1809 (seventh macopoeia Revision Committee by Richard Phillips edition) FRS and colleagues. reputedly because of serious criticisms the number of new drug entities included reflected the made by a London chemist and druggist. suet. The trend to review and ysis and identification. As might be expected. and a more rational naming system for compounds The London Pharmacopoeia 1836 (ninth was used. been said to herald the advent of drug standardisation. of substance purity. upon the London Pharmacopoeia. the need to follow directions and weigh. which had only recently been first used it was stated that alcohol prepared by distillation on a as an anaesthetic agent. It Flores Martiales). quinine and than the previous 1788 edition and the practice of strychnine) and the halogens iodine and bromine. were included. of which 175 were of vegetable Edinburgensium was first produced in 1699. as on animal (including human) material. together with a further 320 compounds and sible that this small first edition of 1699 was modelled preparations which were arranged in product group. atropine. The London Pharmacopoeia 1824 (eighth The last London Pharmacopoeia 1851 (tenth edition) edition) This edition was dedicated to George IV and contin. Indeed.g. the 1824 edition. cyanic acid and ergot). Spongia Usta (burnt regard to the selection of information provided in this sponge. Acidum Sulphuricum replaced the rather ancient as details were included concerning the determination term Acidum Vitriolicum). The binomial system of plant nomenclature tions) and Testae Preparatae (oyster shells used as an was adopted. Ferrum Ammoniacale rather than published earlier as it was in alphabetical order. For example. as were details of temperatures using the antacid). Cornu Ustum (animal rigorous scientific approach had been adopted with charcoal from burnt ivory). The temperatures in entirely responsible. the 1836 edition has replace older nomenclature was also continued (e. This was the last edition of the London Pharma- ued the trend to include the fruits of contempo. water bath from rectified spirit treated with potas- sium subcarbonate should have a specific weight of 0. many Fahrenheit of both sand and water baths were defined new medicaments appeared. Historical perspective | 11 predecessors. ferrous iodide syrup and monographs for a range of compounds.g. there was further evidence that a more ples remained. This increased research editions. in that the pages were substantially proviso that they were still in Latin). hydro- ued. such as lard. This edition was produced on a larger page size Many new alkaloids (morphine. The Pharmacopoeia Collegii Regii Medicorum tained 223 articles. publishing a Latin-to-English translation was contin. It is pos- origin. some intriguing exam- In addition. It was also recognised the ancient and often bizarre materia medica based that many practitioners were less proficient in Latin.815. The 1809 edition was republished with correc. Very few of smaller (approx 8 cm 13 cm). Richard efforts directed at experimental research being actively Phillips FRS (1777–1851). including cod liver oil. However. rejecting some of the more traditional edition) The 1836 edition differed substantially from those nomenclature (e. effort was also reflected in this edition of the ing and measuring instructions in the Pharma. and a number of specific weights were included in the morphine salts. so much the the foreword indicated that a translation of the 1788 mainstay of the older Pharmacopoeias. The Edinburgh Pharmacopoeias The table of contents for the 1824 edition con. together with a number of potent agents (e. which was rich in iodine for thyroid condi- edition. newly developed Fahrenheit mercury thermometer. In this and subsequent conducted around this time. chloroform. copoeia for which the College of Physicians was rary experimental research. . The increase in tions in 1815.g. as it closely resem- ings that are clearly recognisable today (with the bled the early English volumes. survived in Pharmacopoeia would be available soon. This of these supplementary pharmaceutical texts include contained a descriptive list of drugs approved for use Pharm Universalis (1747) by Robert James. which was effectively In 1841 the last edition of the Edinburgh Phar. In texts in Latin in some ways promoted the need for 1839. Clearly. lished A Physicall Directory. This final edition reversed the weighing recom. did not prevent the development of other unofficial Further changes in later editions of the Edinburgh reference works: indeed. However. however. compound preparations and a variety of were given in this edition. . produced in many subsequent editions. By this time much of the older materia any ancient. final edition stipulated that poisons must be dispensed ilar manner to the pharmaceutical customs practised in bottles of distinctive shape. In The 1783 edition of the Edinburgh Pharmacopoeia addition. mendations of 1839 and the Imperial weights and A New London Dispensatory was published by measures system was introduced. the production of official Pharmacopoeia mirrored those adopted in London. The 1851 edition had largely excluded been reached. The pro- because of the perception that this agent was thera. Moreover. an unauthorised translation of the 1618 London macopoeia was published. in some respects The pharmacopoeias produced in Scotland were the Irish Pharmacopoeia was more advanced and for- revised regularly. give instructions on how the purity of drug substances In 1649 Nicholas Culpeper (1616–1654) pub- could be determined. chloroform appeared only three years after stipulated that the measurement of quantities of both its first use as an anaesthetic in 1847. which often then contained additions by guage rather than Latin. Despite the inclu. Further editions were issued in 1826 and 1850. William Salmon (1644–1713) in 1676. and this edition also began to the author. Examples and endorsed by the College for general issue. and avoirdupois medica had been excluded. terparts from London and Edinburgh. ries and many of these texts served to support the need duced in 1793 and 1805 for exclusive use by College for improved teaching and learning experiences in members. no dosage recommendations of simples. prior to the publication of the first London formed by William Withering in 1775. despite having Pharmacopoeia in 1618 all pharmaceutical texts and been removed from earlier editions presumably reference works were technically ‘unofficial’. and by 1774 the sixth edition had ward thinking. this interesting that although the Dublin Pharmacopoeia Pharmacopoeia was largely based upon ancient tradi. ineffective preparations. peutically ineffective.12 | History of compounding The 1699 Edinburgh edition contained details and measures. The together with preparation and compounding details London Dispensatory (1811) by A T Thomson. translations. The and advice concerning equipment and official weights Pupil’s Pharmacopoeia (1824) by William Maugham. and this remained in use Pharmacopoeia with additional comments on the ther- until the first British Pharmacopoeia was issued in apeutic uses of the substances included. weights replaced the troy system previously used. Digitalis was re-introduced into the Unofficial reference works 1783 edition following the groundbreaking work per. English was adopted as the pharmaceutical lan. throughout the eighteenth and early nineteenth centu- duced its own Pharmacopoeia. This work was continually developed to include information on pharmaceutical practice and was produced in a total of The Dublin Pharmacopoeia eight editions up to 1716. However. the solids and liquids should be made by weight in a sim. In this edition there is also an interesting example of eighteenth-century evidence- based practice. chemicals used in therapeutics. It is sion of the latter more advanced preparations. in France at this time. (Pharmacopoeia Collegii Medicorum The trend to produce translations and interpreta- Regis et Reginae in Hibernia) tions of the official London Pharmacopoeia continued The Royal College of Physicians in Ireland also pro. was clearly based in principle on elements of its coun- tional remedies and materia medica. Editions were pro. duction of the first official Pharmacopoeia. This work was 1864. in 1807 an edition was produced pharmaceutical practice and therapeutics. codeine phosphate. Collected appendices contained In the next edition of the British Pharmacopoeia. received an unfavourable reception in the professional amend and republish in response to scientific develop. Subsequent editions and addenda Mr Peter Squire. A statement was included . hormones cal research. third edition in 1885. with chemical substances of botanical origin such as It was published in English and consisted of two parts. dry thyroid. in addition to many inorganic and chemical tests. glycerin of pepsin). pro- The Medical Act (1858) led directly to the production duced A Companion to the British Pharmacopoeia of the first British Pharmacopoeia in 1864. liquid preparations containing the substance in question paraffin and saccharin. and kaolin. being of a similar page size. such as apomorphine hydrochloride. Also. Chemistry (1831) by William Maugham. The active research under- listed monographs for the therapeutic agents. one each for England. a a Pharmaceutical Society representative was also wide range of agents with therapeutic value were appointed to the London subcommittee of the British added to the 1898 edition. together ous pharmaceutical texts. set in the 1864 first edition in that the distinct parts Edinburgh and Dublin Pharmacopoeias. with weights and measures necessary for preparation The second edition of the British Pharmacopoeia and mixing. Historical perspective | 13 the Supplement to the Pharmacopoeia (1828) by S F substances and equipment used in medicines prepara- Gray and the New London Manual of Medical tions and analysis. Under this soon after publication of the first edition of the Act the General Medical Council for Medical British Pharmacopoeia. as quillaia. peutic importance. that the British Pharmacopoeia would be the official The 1898 fourth edition differed from the pattern reference for the British Isles. taken by the Victorians and included crude drugs such which in many ways resembled other contemporane. relevant chemicals. by 1898 exam- to assist with appropriate chemical and pharmaceuti. doses were expressed using both macy. characteristics. Ireland and vitamins (lemon juice) had been included in the and the Pharmaceutical Society. This book was widely con- Education and Registration was set up and given sulted within the profession and after numerous responsibility to publish a book listing medicines and editions was incorporated in Martindale’s Extra compounds. Scotland. cascara and strophanthus. including bismuth salicylate parations and compounds considered to be of thera. fruits of the extensive overseas exploration under- The result was the 1864 British Pharmacopoeia. thyroid solution) established. facturers rather than being encompassed as part of the copoeia and to appoint paid pharmaceutical experts general pharmacy-based activity. published in 1914. the Pharmaceutical Society’s repre- The British Pharmacopoeia (BP) sentative for British Pharmacopoeia development. their method of preparation together Pharmacopoeia. in order to assist with British Pharmacopoeia. and the need to alter. physostigmine sulphate and both in alphabetical order. Part I (161 pages long) strychnine hydrochloride. chemicals and minerals. ples of enzymes (pepsin. It was clear from the monographs in Medical Council in November 1858 a decision was this edition that most of the manufacture of chemical made to ensure involvement of the Pharmaceutical substances had been taken over by wholesale manu- Society in the preparation of the British Pharma. details of information required in the practice of phar. including symbols. The name of the work was specified as appeared in 1867. at the first meeting of the General amalgamated. aloin. superseding the London. As might be expected given Pharmacopoeial development. and in December 1858 the impetus for research into medicines at the time. since the first edition apparently The British Pharmacopoeia. weights and measures and metric and imperial units. Many resulted from the Pharmacopoeia. coca. Four Pharmacopoeia committees were (pancreatic solution. a ments was recognised and empowered. giving taken at this time also yielded a range of other organic details of material sources. Part II (233 pages long) listed pre. followed by an addendum in The Medical Council Act (1862) further stipulated 1890 and a fourth edition in 1898. community. (Part I Materia Medica and Part II Preparations) were Significantly. An addendum was published in 1874. were reduced in produced in 1955. some of which were compiled to address the also appeared. monographs referring to the products of pharmaceu- tinued to use both imperial and metric measurements tical research and development and to actively remove and firmly established the principle of ‘solids by preparations of little or no value. and capsules. which reflects the It was a further 18 years before the appearance of degree of work required to update the previous edi- the next revised edition of the British Pharmacopoeia. notably those considered to be sedatives Pharmacopoeia were produced between 1936 and or tranquillisers. the eighth edition of the British Commission of six members was convened. both hard and soft. In reality it was to (GMC) actually described the production of the sev- be well over 50 years until this happened. as insulin and antitoxins as defined by the Therapeutic The 1958 edition continued the trend to add Substances Act (1925). the Gov. against typhoid and tetanus. As might be expected. the GMC obvious disturbances to political and social structures also indicated that new editions of the British caused by World War I and partly because times of Pharmacopoeia should appear every five rather than serious conflict tend to accelerate developments in 10 years. including certain of the sex hormones that ‘in the near future the (metric) system will be and. necessitated by the significant sions to the range of antibiotics and immunological technical and scientific advances made before and agents. though. The General Medical Council adopted by British prescribers’. The seventh edition of the British Pharmacopoeia An addendum to the 1958 edition in 1960 included was finally produced in 1948 after major revisions of a number of monographs describing important exten- the previous version. English Hampshire. A number of monographs It is clear. was a significant increase in the appearance of psycho- Seven addenda to the 1932 edition of the British active agents. British Pharmacopoeia of 1864’. macist at University College Hospital. ciple further to enable the date of implementation of sideration. developments in many developments. At this time. enth edition as ‘a more complex and laborious task ernment only in 1965 announcing support for the than any of its predecessors. particularly with regard to the analysis were reflected by the inclusion of an increased biological and serological agents that had had a sig. tion. expressing the expectation developments. London. who had previously been the chief phar. Reflecting on the workload imposed by the rapid in 1932. This edition con. Certain categories of Again only one addendum to the 1953 edition was preparation. number of assays. Such a long interval arose in part through the expansion of pharmaceutical discoveries. although in some cases an abbreviated Latin synonym Naturally the 1932 British Pharmacopoeia contained was retained. not excluding the original metrification of the UK ‘within 10 years’. such the ninth edition in 1958. before the implementation of with the determination of therapeutic substances. were added. during the war period. nificant impact in World War I with vaccination were introduced as a new dosage form. Naturally. The Medical Act (1950) extended this prin- both the medical and pharmaceutical fields: the con. The preparatory work to produce the 1932 British In accordance with the new five-year implementa- Pharmacopoeia began in 1928 when a Pharmacopoeia tion interval. which contained new disintegra- number and details of standards and tests associated tion tests for tablets. notably. replaced Latin in the titles used in the 1953 edition. penicillin. A number of radioactive isotopes 1945. developments. evaluation and assimilation into the British future British Pharmacopoeias and addenda to be Pharmacopoeia of the significant therapeutic and determined in advance. there weight and liquids by measure’. such as a parenteral poliomyelitis vaccine. principally to allow those practice advances made during and following World involved in drug manufacture to have studied and War I took time to effect. there was an appropriate need for alternatives to official BP medicinal products extension and modification of assay details and pro- in response to the failure of supply lines for some cedures to embrace these new pharmaceutical pharmaceuticals during World War II.14 | History of compounding that qualified this action. such as wines and pills. prepared for new standards. the were included to address new drug discoveries and British Pharmacopoeia was no longer considered to . Pharmacopoeia was issued in 1953 after only one time secretary of the Commission was Dr CH addendum to the previous edition in 1951. The full. that by the late 1950s. and other texts were more often utilised. 1923 and 1934. which also detailed International mal origin. It was recognised that many non- Subsequent editions were issued in 1949. for example accordance with section 99(6) of the Medicines Act the ‘ml’ was used rather than the ‘cc’. was largely based upon the British Pharmacopoeia together with information from various respected hos- The British Pharmaceutical Codex (BPC) pital formularies and reference works from the USA and Australia. official texts had attempted to provide information 1959. 1963. formulae for preparations and information to cals. particularly in other parts of the Empire. uses. In 1903 the Council of the Pharmaceutical Society decided that an appropriate single-volume work should be developed in order to provide accurate The International Pharmacopoeia (World information about medicines commonly used Health Organization) throughout the British Empire and those officially The first volume of the International Pharmacopoeia recognised in France. details of pharmacy other than by those involved in quality for tests. Germany and the USA in addi. were included. The British Pharmacopoeia is still published on the The text was arranged with substances in alphabetical recommendation of the Medicines Commission in order and contained some innovations. facilitate prescribing and dispensing. and agents excluded despite being Insurance Acts. backing. 1954. French translations. These critics cited issues such as the a separate section. information on mechanisms of action and assurance or large-scale manufacture of pharmaceuti. was produced in 1951 in Latin with English and tion to the UK. The second volume followed in 1955 and con- as ‘An Imperial Dispensatory for the use of Medical tained details and formulae for preparations involving Practitioners and Pharmacists’. dressings that had been accepted in accordance with the exclusion of medicines thought to be valuable but the Drug Tariff as part of the National Health not yet established. Historical perspective | 15 be a reference text useful in the daily common practice sources. This trend was extended in the failure to embrace medicines used elsewhere in 1940 BPC supplement. histology and chemical composition. which specifically referred to the world. Details of these substances. issued in 1959. In inadequacies of official texts such as the British the latter edition. which was described assays. The content 1968. tests and biological Pharmaceutical Codex (BPC). 1968 and 1973 and the content was con- about such agents but none had robust professional tinually refined to reflect current therapeutic practice. tion of monographs on drugs and chemicals with maceutical Society in 1907 of the first British appendices dealing with reagents. in common use. The range of Pharmaceutical Codex contained monographs on agents and information was extended in a Supplement medicinal substances of chemical. vegetable and ani. This volume consisted of a collec- The response was the publication by the Phar. . surgical dressings were included as Pharmacopoeia. By the end of the nineteenth century leading practi- Further editions of the British Pharmaceutical tioners of pharmacy were highlighting some perceived Codex were produced in 1911. The 1907 British the agents specified in the 1951 volume. including Biological Standards. . This The following sections are devoted to descriptions embraces both the high level of technical ability used of the nature. troches) 26 Other old pharmaceutical equipment 38 Mucilages (mucilagines) 26 Old pharmaceutical containers 38 Oxymels (acid honeys) 26 Glass phials 38 Pills (pilulae) 27 Medicine bottles and containers 39 Plasters (emplastra) 28 Bulk liquid containers 40 The activities of an apothecary or pharmacist in com.2 Obsolete dosage forms. and the appropriate knowledge base required to suc- pounding a medicine using traditional methods was cessfully undertake compounding procedures that often referred to using the term secundum artem. result in a medicine acceptable to patients. equipment and technology . equipment and methods of preparation Obsolete pharmaceutical preparations Poultices 28 and preparative methods 18 Resins 28 Galenicals 18 Snuffs 29 Bougies 18 Syrups 29 Cachets (capulae amylaceae. erally meaning ‘to make favourably with skill’. oblata) 19 Tinctures (tincturae) 29 Collodions 20 Vinegars (aceta) 32 Confections 20 Waters (aquae) 32 Decoctions (decocta) 20 Wines (vina) 34 Extracts (extracta) 20 Old pharmaceutical equipment 34 Eye discs (lamellae) 21 Weighing and measuring 35 Glycerins (glycerita or glycerites) 22 Comminution 36 Infusions (infusa) 22 Equipment for the manipulation of Juices (succi) 26 formulations 38 Lozenges (trochisci. preparation. lit. Although it was likely that the ther. inserted into the urethra. The ancient Greek physician Galen (Claudius Obsolete pharmaceutical Galenus of Pergamum.g. to prevent the manufactured bougie from sticking to the mould. which evolved before the ability Bougies to separate active ingredients accurately. solutions. extraneous constituents present page 31). albeit in specia. active constituents was either technologically impos. They are presented here in part to satisfy histor. cals. compounds and formulations. true galenicals were phar- tury. infusions.19. however. maceutical preparations obtained by macerating or ical interest and partly as a repository of methods and percolating crude drugs with alcohol of an appropriate skills that would otherwise be lost completely to the strength or some other solvent (menstruum). Some examples of galenicals have been retained in sible or prohibitively expensive. inert and other undesirable constituents of the plant in lised situations. or animal sources. it was practice today and are obtained from alkaloid-bearing commonly believed by early practitioners that under plants. waters. to name any type of preparation modern suppository (Figure 2. free from inert Galenicals material and therapeutically efficacious as well as Most of the active constituents of traditional extem. became com. leaving the still be encountered in current practice. in impure forms of medicines could exert beneficial actions on the therapeutic ingredients. This is why various galenicals. preparations and preparative hence the term galenicals. In addition. Historically. the solid phase (marc). local or systemic effect in a similar manner to the and often incorrectly.) irrespective of whether drug forms. although not true galenicals. are considered in Part 2 of this book. Bougies are solid preparations that are designed to be monplace in pharmaceutical compounding. which general pharmaceutical world. extracts. tinctures. . The hinged mould is silver-plated to provide a smooth surface. Since that time. twentieth century. concentrated. most of it is an extract of a crude drug or a solution of chemi- which have become defunct during the twentieth cen. Aromatic waters. AD 131–201) was the first to devise solutions of the active constituents of plants. nose or ear in order to exert a Today. was carefully selected to remove as completely as pos- The preparations. Figure 2. ‘galenicals’ is a term that is applied loosely. etc. pharmacists methods have tried to improve upon Galen’s techniques and prepare galenicals that are stable. isolation of discrete the following sections. for ease of handling. e. forms and formulations that may sible only the desired active components. Belladonna Tincture BP (see Example 2.18 | History of compounding associated with the compounding of some traditional (elixirs. Examples of true poraneously prepared products originated from plant galenicals include decoctions.1). apeutic effects of these preparations could be attrib.1 Bougie moulds. will also be outlined in uted to one active ingredient. vinegars and oxymels. certain circumstances. so that the roller could be used to moisten the cachets for sealing.2). oblata) urethra. The trough would contain damp lint. early twentieth century. piece of wet felt. or moist air by storing in a tightly closed container in a In its most well-developed form a cachet com- cool place in order to maintain their integrity. with a point at one end. Finished bougies were then often The powder was then placed into the spoon-shaped rolled in lycopodium powder after removal from the depression and the corners of the wafer folded over to mould in order to stop them sticking to surfaces. The British shaped.2 Cachet machines. they should be made with Theobroma whereas. Figure 2. In on insertion. A cachet could be sealed by moisten- for the medicaments that were to be incorporated into ing the flanges. enclose it. Developments from this prac- bougie with an elongated bulb near the tip that reput. but most pharmaceutics textbooks of the compounded using Theobroma Oil as a base.25 cm in length and weighed for the filling and sealing of larger numbers of cachets. approximately 2. Obsolete dosage forms. prised two lenticular or spoon-shaped flanged discs Nasal bougies were similar to urethral bougies but made from rice paper. The drug substance was placed shorter. then its period (e. and the one at the front is for wet seal cachets. Generally a glyco. sized bougie formulated in a gelatin base.5 cm in length. and weighed within the saucer-shaped depression in one half of the approximately 1. References disagree on the glycerinated gelatin and was designed to be pencil common base used for aural bougies. When it had softened. drug powders by encapsulating the offending sub- Henry Wellcome devised a version of the urethral stance in bread and jam. were conical type seal). Glyco. . If a bougie was Oil BP base. The gelatin versions were better than those moulded in oil as they were more flexible. which aided insertion into the Cachets (capulae amylaceae. also called ear cones. a tablespoon warmed before pouring the mass in order to facilitate was passed underneath the wafer and it was lifted out. Sophisticated sets of apparatus were devised in shape. order to administer a powder the dry wafer was The mould for the urethral bougie had to be floated on water. a 4 g version was 14 cm long.g. equipment and methods of preparation | 19 The urethral bougie was generally formulated in between 250 and 400 mg. of glyco-gelatin bases. usually by quickly passing them over a the product. and then sticking them together (wet- Aural bougies. wise directed. complete filling. They were usually prepared cachet and was sealed in by placing the second half on using a glyco-gelatin base as this was more suitable top (Figure 2. 1950) suggest the use weight was approximately half that of an equivalent. Pharmaceutical Codex 1949 stated that unless other- gelatin 2 g bougie was approximately 7 cm in length. usually about 1. tice involved the production of thin wafer sheets from edly reduced the likelihood of involuntary expulsion flour and water which could be dried and stored. Cooper and Gunn. The machine on the right is for making dry seal cachets. If a firmer consistency of the bougie was Cachets were developed from the early practice of required then acacia mucilage could be substituted masking the taste of unpleasant bitter or nauseating for either glycerin or water in the formulation. Water was then poured onto the spoon and gelatin bougies had to be protected from excessively dry the packet swallowed.5 g. These are liquid preparations. containing highly volatile solvents (usually a base solution of pyroxylin (soluble gun-cotton) in a mixture Formula: of ether and alcohol) that evaporate to leave either a Chondrus 25 g mechanical or a therapeutic film. loss of active principles. Although almost obsolete. Hard ligneous drugs were using a variety of processes (expression. though there was a certain ‘knack’ to this procedure.1 Decoction of Chondrus Collodions BPC (Decoctum Chondri) (BPC 1949. were boiled with water for a specified time. maceration. page 111). impurities and boil with 1200 mL of water for 15 minutes. alcoholic. ethereal. . If decoction was followed by evap- oration. if neces- Confections sary. more drug substances were incorporated. intended for external page 1091) use. A decoction differs from an infusion in that one or more crude drug bases. times during the process. or more.20 | History of compounding These included pourers to avoid powder contaminat. order to render them soft. 1949. This process left an aqueous preparation sim. Clearly few drugs Cachets had to be moistened before swallowing in were suited to preparation in this manner. A dry-seal type of cachet was also developed that The object of a decoction was to produce an aque- consisted of a body to hold the powder contents and a ous solution containing soluble active drug principles cap that interlocked over the body to form a seal. made up to volume with more distilled water. Use: As a demulcent in the treatment of irritating Decoctions (decocta) coughs. soft. solid preparations into which one or when cool. which was passed through the original filter to ensure Decoctions fell from use in the early 1950s and the that as much extract as possible had been removed from last official examples of formulae appeared in the BPC the marc. then a solid or semi-solid extract was produced. either whole or suitably prepared. should be Freshly Prepared (see Chapter 6. acetic or ammoniated). Confection of Senna BP). pour sufficient water over the contents of Confections (older terms: conserves. while offering a 30–120 mL. usually 10 minutes or until a given volume was obtained. Example 2. that were not degraded by heat. with the addition of aromatics and volatile ing the flange of the cachet and specialised holding and oils near the end of the process in order to minimise sealing devices. Flexible Collodian BP and Salicylic Acid Method: Collodian BP are still listed in the modern British Wash the chondrus in cold water to remove Pharmacopoeia (2009). Dose: tration for bitter or nauseating drugs. It should be Freshly Prepared. ilar to ‘clear soup’. added first. Strain while hot and. sweet. convenient method of preservation (e.g. They were designed to provide an agreeable method of adminis. elastic and slippery. if necessary after very susceptible to decomposition and therefore they cooling. Collodions had to be Water to 1000 mL applied to the skin using a soft brush. Extracts (extracta) Where a number of ingredients were to be included Extracts are produced by the action of various solvents in the decoction then they were added at different (aqueous. electuaries) were the strainer to produce the required volume thick. The Because decoctions are aqueous products they are preparation was then strained and. which was often an alkaloid. The most com. as powdered vari- Extracts were intended to contain the active prin. percolation). although granular dried extracts were pre- quently termed succi spissati (inspissated juices). The active ingredient. reserving the first 850 mL of per- Solid extracts varied in consistency depending on colate. allow to stand for not less semi-sticky masses formed by concentration from a than 12 hours and filter. soft extracts often Because of its astringent properties. dissolve it in soft extracts. with a consistency between that of a pill the reserved portion. This also means that the of haemorrhoids. in coarse powder 10 oz Alcohol (90%) a sufficient quantity Example 2. page 26). equipment and methods of preparation | 21 decoction. Liquid Liquorice Extract BP. or dry extracts. liquid extract. Formula: Hamamelis. Eye discs (lamellae) Example 2. Soft extracts were produce 1000 mL. In general. Storage was less likely to cause significant and evaporation. inert matter present. depending on preparation and storage. They were termed either the consistency of a soft extract. add sufficient alcohol to mass and a paste. they produce liquid. ferred to those that were powders. producing a tough mass that and its preparations are used in the treatment was difficult to handle. extracts contained a Liquid extracts are still commonly used in extem- higher proportion of active drug principles than equiv. would be released for a local effect.2 Extract of Cannabis BPC Lamellae were small discs of a glyco-gelatin base that (Extractum Cannabis) (BPC 1949. decoctions or tinctures. the main example being alent infusions. in moderately coarse powder 1000 g Dose: Alcohol (45%) to 1000 mL 1/4–1 gr. Formula: Cannabis. . page 1118) where they would be allowed to dissolve in the lach- rymal secretions. It is also used in toiletry strength of a soft extract could vary significantly preparations. Method: Exhaust the hamamelis with the alcohol by percolation. Obsolete dosage forms. the resultant extracts were fre. Exhaust the cannabis by percolation with the page 682) alcohol (90%) and evaporate to the consis- tency of a soft extract.3 Liquid Extract of Hamamelis BPC (Extractum Method: Hamamelis Liquidum) (BPC 1973. evaporate the subsequent percolate to their degree of concentration. poraneous compounding. eties were more likely to absorb moisture from the air ciples of crude drugs while minimising the amount of and become a solid block. semi-solid or solid products. were intended to be placed onto the cornea of the eye. In addition. hamamelis hardened on storage. problems. which may be followed by Dry extracts replaced soft extracts as the solid evaporation with or without vacuum assistance to extract of choice as these could be standardised. Liquid extracts are usu- mon extracts encountered were either solid or liquid ally prepared by the ‘reserve percolate process’ (see extracts. Where varied less in strength and were generally easier to the juices of fresh plants were obtained by expression handle. They have fallen from current use because it was difficult to standardise the degree of Use: ‘softness’ and therefore their consistency with any degree of accuracy. Decant pressed. The prin. The vol- Exhaust the liquorice with chloroform water ume of the product depends on the quantity of men- by percolation. The degree of comminution of the drug. which should not be and set aside for not less than 12 hours. vessels (latterly glass was used) (Figure 2. 1905.g.4 Liquid Extract of that was not otherwise readily soluble. page 111). If hot water was added to prepare the Used in cough mixtures and to disguise the infusion it would be weighed into a previously tared taste of nauseous medicines. When the specified infusion time had elapsed. Formula: Infusions containing a drug that was freely soluble Tar 65 g or those containing a high proportion of starch were Magnesium carbonate 125 g prepared with cold water. They were pre- Method: pared by macerating drugs in water for short periods of time. unpeeled. Add to the nature of the drug and the constituents to be this liquid. varying from 15 minutes to 2 hours. mix the temperature used for the preparation of the infusion two liquids and evaporate until the weight per and the length of maceration chosen depended upon millilitre of the liquid extract is 1. designed pouring spouts. These had in-built supports for the Glycerins (glycerita or glycerites) crude drug substance positioned at an appropriate These were produced by dissolving or incorporating level in the container and also featured specially substances in glycerin (or glycerin solutions). If the drug sank to the bottom of the vessel the mixture would need occa- Use: sional stirring. Infusion devices were often cipal use of glycerins was to provide a simple and rapid made by customising tea or coffee pots. page 449) could be easily diluted with water or alcohol without precipitation. filter the remainder. page 1351) infusion. of alcohol (90%). The supernatant formed the (Remington. when cold. and warmed vessel to prevent cracking of the measure. The drug was added to the vessel usually suspended in some way Dose: or enclosed in muslin (like a modern teabag) so as to be 2–5 mL.198 g.5 Glycerite of Tar removed as quickly as possible so as to allow the prep- (Glyceritum Picis Liquidae) aration to cool before use. Formula: Liquorice. in coarse powder 1000 g Infusions (infusa) Chloroform water a sufficient quantity Infusions are dilute solutions containing the water- Alcohol (90%) a sufficient quantity soluble extracts of vegetable drugs. Alsop’s Infusion Jar. Often a layer of cloth was wrapped around the infusion container in order to reduce heat loss and hence aid the extraction process. one-fourth of its volume extracted. filter.3). Fresh infusions should be Glycerin 250 mL dispensed within 12 hours. which was generally unstable and needed to be Freshly Prepared (see Chapter 6. Boil the percolate for 5 minutes struum retained by the marc. just below the surface of the water.22 | History of compounding method of producing an aqueous solution of a drug Example 2. Allow to stand for not less Infusions were usually prepared in earthenware than four weeks. Squire’s Infusion Mug). . the the clear liquid. Sometimes highly concen- Alcohol 125 mL trated forms of infusions were prepared. Water to 1000 mL A number of types of special infusion apparatus were developed (e. the product was strained and the marc Example 2. Many of the Liquorice BP (Extractum Glycyrrhizae glycerins were made in a concentrated form that Liquidum) (BP 1963. J. Use: trated infusions from which infusions can be prepared An astringent used in internal mixtures to treat by diluting one volume of concentrated infusion to ten diarrhoea.8 Compound infusion of horseradish (Infusum Armoraciae Compositum) (Pharmaceutical Example 2. any formula that predates 1968 will be required to be diluted to eight volumes with water. Use: Use: Used as a counterirritant and vesicant for To treat hysteria as it is said to depress the external application and as a carminative in nervous system. then strain and add the spirit. bruised 30 gr Distilled water. bruised /2 oz Distilled water.3 Half-pint Denby earthenware infusion jar.6 Infusion of Valerian BPC Journal Formulary. volumes with water. boiling 10 fl oz Method: Infuse in a covered vessel for half an hour and Figure 2. The BP and BPC recommend the use of concen. This applies to all formulae for concentrated infusions since reformulation in 1968.7 Infusion of Catechu BP (Infusum Catechu) (BP 1885. Example 2. Dose: 1–2 fl oz. equipment and methods of preparation | 23 Example 2. 1904. at 150–180 F 20 fl oz Distilled water. page 205) Formula: Catechu. small amounts. . Bourne and Son Ltd. page 22) (Infusum Valerianae) (BPC 1911. Obsolete dosage forms. strain. boiling 1 pt Method: Method: Macerate the seed and root for 2 hours with the Infuse in a covered vessel for 15 minutes and water. in coarse powder 160 gr Cinnamon bark. sliced 1 oz Formula: Black mustard seed 1 oz Compound spirit of horseradish 1 oz 1 Valerian rhizome. 1 /2–1 fl oz. Also used as a carminative. probably nineteenth century. page 1224) Formula: Fresh horseradish root. made by strain. Dose: Dose: 1–2 fl oz as a warm stimulant. 24 | History of compounding Example 2. This is because both the preparations contain volatile consti- tuents that would be dissipated by evaporation. 48 hours and press out the liquid. and also because in the percolation process the active ingredients must be ground more finely and in the comminution process there would be further potential loss of volatile constituents. Dose: 2. As a vehicle for gargles containing alum or tannin. macerate for Dose: 24 hours. boiling 10 oz Alcohol (25%) 1350 mL Method: Method: Mix the red rose petal with the boiling water in a covered vessel. dried and broken 1/4 oz Dried bitter orange peel. Use: Two different methods of producing a concen. Macerate the dried bitter orange peel in 1000 mL of alcohol in covered vessel for infuse for 15 minutes.5–5 mL. The dried bitter orange is cut into small pieces in order to expose the oil glands embedded in the peel.11) are prepared by double maceration. page 704) Formula: Formula: Red rose petal.10) and Concentrated Compound Gentian Infusion BP (Example 2. Flavouring and as a bitter with carminative trated infusion have been used in Examples 2. press out the liquid. Allow the mixed liquids to stand for not less than 14 days and Use: then filter. 500 g Dilute sulphuric acid 60 m (minims) cut small Water.10– properties. . and add it to the 1 /2–1 fl oz.10 Orange Peel Infusion Rose BPC (Infusum Rosae Acidum Concentrated BPC (Infusum Aurantii Recens) (BPC 1949. page 1156) Concentratum) (BPC 1973. product of the first pressing.12: double maceration and reserve percolation. To the marc add the remainder of the alcohol. and strain. The Orange Peel Infusion Concentrated BPC (Example 2.9 Fresh Acid Infusion of Example 2. where the filtrate is the finished product and no evaporation process is used. add the dilute sulphuric acid. 2. Concentrated BPC (Infusum Senegae hol (25%). days. the Senega Infusion Concentrated Concentratum) (BP 1973. this is likely to contain a significant amount of soluble Use: matter.1). The resultant liquids from both is used with other expectorants in the treat- macerations are combined and allowed to stand for 14 ment of bronchitis. evaporate to a syrupy con- sistence.12 Senega Infusion vessel for 48 hours with 1000 mL of the alco. Dose: In double maceration. A bitter to stimulate gastric secretion and stim. Senega. a Dried lemon peel.12) is made by the ‘reserve percolation’ process (Box 2. Continue percolation until a further 1000 mL ulate appetite. press out the liquid. woody drug.5–5 mL. (Infusum Gentianae Compositum By contrast. Alcohol also acts as a preservative. To the pressed Concentratum) (BPC 1973. Obsolete dosage forms.5–4 mL. after which it remains clear and Compound Gentian Infusion BP bright. cut small 125 g therefore more difficult to extract. and mix. cut small 125 g tough. in coarse powder 500 g Dilute ammonia solution a sufficient quantity Alcohol (25%) to 1000 mL Dose: 1. which slowly precipitates on . page 704) marc.11 Concentrated the liquid is filtered. has been collected. add 200 mL of the alcohol (25%). press. equipment and methods of preparation | 25 standing. Allow to stand for not less than 14 days and then filter. gradually add dilute ammonia solu- tion until the product is faintly alkaline. discour- aging the development of moulds and preventing fermentation. cut small and bruised 125 g Dried bitter orange peel. The second maceration process is intended to To irritate the gastric mucosa and give rise to a achieve a better extraction through addition of men- reflex secretion of mucus in the bronchioles. Method: Macerate the gentian. page 217) BPC (Example 2. the dried bitter orange peel and the dried lemon peel in a covered Example 2. which is generally Formula: restricted to the production of a concentrated infu- sion where the original drug is a hard drug and Gentian. Method: Extract the senega with the alcohol by perco- Use: lation. there are no volatile constitu- Alcohol (25%) 1200 mL ents to be lost and therefore a method employing heat is suitable. extracts most of the soluble matter but leaves an amount of liquid that is inseparable from the marc. mac- erate for 24 hours. With senega. the first maceration process 2. The expression process expels mucilaginous and albuminous matter. reserving the first 750 mL of percolate. and add the liquid to Formula: the product of the first pressing. water. dissolve the residue in the reserved portion. Allow to stand for volatile oils are more soluble in alcohol than in not less than 14 days and filter. It struum to the marc. add sufficient of the alcohol to produce the Alcohol 25% is used for the menstruum because required volume. On completion of the precipitation process Example 2. hemlock. freshly boiled and cooled 150 mL They were prepared by mixing the active substance Purified honey to 1000 mL with one of four bases (the lozenge mass). containing a very low con. The lozenge mass was rolled into a flat sheet of appropriate thickness on a lozenge board using a cylin. henbane. two comprised sugar and gums with rosewater. There are many examples of oxymels formulated with Juices were prepared by expression from fresh natural active ingredients. adhesive aqueous solu- is achieved mainly by the 24-hour maceration tions or extractions of gums.1 Reserve percolation for a given cutter size. effect on the active constituents. which gen- erally contained sugar and mucilage. Method: prised sugar and gums in a blackcurrant paste.5–10 mL. The lozenge weight was . products (e. dandelion). as water-miscible bases for dermatological prepara- orated to produce a soft mass or syrupy liquid. cines for internal use. and less concentrated and the final percolate page 924) that are used as thickening agents in medi- may be very weak. Since mucilages are prone to decomposition they colate to heat. tolu tincture and water. page is added. Use: drical roller. tions and as lubricating agents for catheters and some which is then added to the strong percolate. page 764) Lozenges were solid dose forms designed to dissolve slowly and disintegrate in the mouth. Finished lozenges were then Demulcent and sweetening agent. belladonna. only 70–80% of the active con. Oxymels (acid honeys) Oxymel is the term applied to purified honey (Mel Juices (succi) Depuratum) to which acetic acid has been added. viscous. 2. and shaped lozenges were cut from this using a metal cutter. troches) 1973.26 | History of compounding determined by the thickness of the flat sheet of mass Box 2. which may have a detrimental should not be made in quantities greater than required. used as suspending agents for insoluble substances in When a concentrated preparation is mixtures. Mucilages (mucilagines) stituents are obtained. base Mix thoroughly. This high concentration Mucilages are thick. When a crude drug is extracted by the perco- lation process. Mucilages were traditionally centration of active ingredient. Base one com. lemon. This method avoids subjecting the whole per.g. base three was a simple base of sugar acacia and water.13 Oxymel BPC (BPC Lozenges (trochisci. Subsequent percolates become less 854) and Mucilage of Tragacanth BPC (BPC 1949. continuous phase of an oil-in-water emulsion system. acacia. Example 2. weight checked and dried. the first A mucilage of starch has been used for its emollient strong percolate is reserved. They were used Formula: principally for drugs exerting a local action in the Acetic acid 150 mL mouth and throat. They have also been used to thicken the required. There are two official process when the first quantity of menstruum mucilages: Mucilage of Acacia BP (BP 1953. trated infusions and liquid extracts. Purified water. The subsequent effects on the skin and other mucilages have been used weaker percolates are then collected and evap. broom. base Dose: four comprised sugar. surgical instruments. such as in the case of some concen. To every 3 volumes of this solution add contain glucose. solid. which gave the mass liquids and heat to boiling to coagulate the appropriate consistency of adhesiveness.14 Squill Oxymel BPC relatively easy to make and compact in quantity. a pill base or Method: mass was constructed from which the prescriber often directed that a given weight of mass should be made Macerate the squill with the acetic acid and into a specified number of pills.5–5 mL.4). The required weight of mass was then rolled into an elongated cylinder on a pill tile. water for seven days. were stable for long periods and were easy to administer. equipment and methods of preparation | 27 with smaller volume doses. The latter was often used as a preservative and might be omitted if only a small batch of pill mass Dose: was being compounded. The cylindrical Figure 2. Use: The active ingredients and excipient were tritu- rated in a mortar with a special pill pestle and kneaded Mild expectorant in cough mixtures. Small quantities of mass were rolled using a pill ovoid or lenticular shape.4 Pill-making equipment. oral dose forms of a globular. firmness expressed cell contents and then filter whilst and plasticity. page 765) masked unpleasant tastes and odours. Formula: It was only during the twentieth century that the poor bioavailability characteristics of pills as a dose Squill. . into an homogeneous mass that could be divided into the desired weight (Figure 2. (BPC 1973. spatula that had very little ‘spring’ and featured a mon oral dose form in the nineteenth century for drugs broad end or a flat impervious board. bruised 50 g form were discovered: pills were as likely to pass Acetic acid 90 mL or sufficient quantity through the gastrointestinal tract unaltered as to dis- Purified water. powdered acacia and ben- 7 volumes of honey and mix thoroughly. Pills were small. They were perceived to be Example 2. Mix the drained and expressed ingredients and the excipient. zoic acid. very adhesive liquid that was usually prepared in advance of compounding the pills. Obsolete dosage forms. nineteenth century. particularly Purified honey a sufficient quantity when used in a coated form. Strain the liquid and The pill mass consisted of two parts: the active press the marc. In order to compound pills by hand. A generic pill excipient would probably hot. This excipient formed a col- 2. freshly 250 mL boiled and cooled integrate and deliver active ingredients. glycerin. which often incor- Pills (pilulae) porated a measuring scale to aid cutting and division. They were the most com. ourless. The upper and lower describe both the adhesive mass itself and the com- boards could be interfaced so that the grooves corre. Poultices Pills were often coated with a variety of substances Poultices were preparations of a thick. They are soluble in were often given a sugar or pearl (using finely pow.28 | History of compounding Figure 2. rendered the pill more attractive Resins and. area on a cloth in order to draw infection. added to their Resins are solid preparations consisting of the resinous therapeutic efficacy. intended for external application to the skin. a plaster was an adhesive substance shape using a pill roller (resembling interlocking jar that required the aid of heat to spread it and was lids) or between the fingers. washed with water. nineteenth century. To manufacture resins the vegetable matter is ficult to accomplish on a small scale. using a special pill machine. remaining soft and pliable pieces. It should be noted that the term ‘plaster’ would grooves of the lower board. chamois. such as gold or silver leaf. which can be subsequently to prevent freshly made pills adhering to each other. Different sized pills could be cut by using dif. A plaster Larger quantities of pills were generally made mass (often containing plant mucilages) was melted. pleted spread plaster. The coating of pills effectively disguised unpleas- ant tastes and odours. An example . A cylin. in the case of precious metals. water. linen or calico cut indented with hemispherical grooves (cutters). circular or (or in some instances a weaker alcohol solution). to a specific size and/or shape as ordered by the pre- drical ‘pipe’ of pill mass would be laid across the scriber. semi-solid base.5) on hardwood boards on which were mounted brass plates plaster leather (sheepskin). pill mass was then cut either by hand or using a pill Plasters (emplastra) divider (a grooved roller) and then rolled into the final In this context. sponded. A light centrated and poured into water. and the upper board had handles which The plaster was firm at room temperature but allowed the compounder to cut the mass into uniform spread easily when heated. ferent sized cutting plates. or the machine by use of a dusting powder such as rice flour. This results in the coating of dusting powder was included in the pill box precipitation of the resin. without melting when in contact with the skin. In square box which was preferably made so shallow that order to isolate the resin the alcoholic extract is con- the pills could not lie on top of one another. chocolate or kera- tin. subjected to an extraction process using 90% alcohol Pills were usually dispensed in a flat. This consisted of two then spread using a hot plaster iron (Figure 2. Hand spreading was largely replaced by a mechan- Pills were prevented from sticking to either the tile ised process in the very early twentieth century. alcohol and in most organic solvents but insoluble in dered talcum or French chalk) coating which was dif. Commercially produced pills constituents of vegetable matter. which was allowed to evaporate). gelatin or varnish (by treat- which were often heated and applied to a body part or ing with a solution of sandarac in ether and alcohol.5 Plaster irons. dried and powdered. This is because of action.7). The resultant tincture is clarified Figure 2. acetone or alcohol) and then concentrating the flavourings or vehicles for extemporaneous prepara- percolate until the solvent has all evaporated. Snuffs Tinctures are particularly useful intermediates as A snuff is a prepared powdered drug that is sniffed they can. in most cases. equipment and methods of preparation | 29 of a resin produced in this manner is Podophyllum concentrations of sucrose prevented the decomposition Resin BPC. Tolu Syrup BP). be kept for long periods with- vigorously up the nose for a local and/or systemic out deterioration or loss of potency. ture is then strained. Tinctures are alcoholic solutions of drugs prepared by adding alcohol (or occasionally ether) to a substance using maceration or percolation (Figure 2.6 A twentieth-century syrup bottle and an eighteenth-century creamware (ceramic) syrup jar. Lemon Oleoresin BPC is an example of a prepared oleo resin. for example Blackcurrant Syrup BP.g. where the ingredients are Syrups are concentrated solutions of sucrose or other placed in an enclosed container with the whole sugars at a concentration of at least 45% m/m. amount of the solvent and are allowed to stand for Flavoured syrups provide a sweet vehicle to mask the seven days with occasional stirring. Capsicum tions. The resulting mix- taste of nauseous medicaments. which is concentrated from the stem of Commiphora molmol (Engler). Sucrose also cutting into the trunks of trees in which they occur. fungi and moulds was inhibited. extemporaneous dispensing and thus form a stock Prepared oleo resins are concentrated liquid prep. Syrups were particu. Gum resins are natural exudates of plants that are a mixture of gum and resin. which is found in 80–90 species of Pinus and is used to Medicated syrups are made of ingredients used in produce Turpentine Oil BPC.6). the preservative properties of the alcohol that is used in their preparation. the reducing sugars glucose and fructose. and the two larly popular in older formulations as high liquids are combined. solution of certain drugs (e. An example is Myrrh Tinctures (tincturae) Resin BP. Syrup BP and Orange Syrup BP (Figure 2. retards oxidation because it is partly hydrolysed into The best-known natural oleo resin is turpentine resin. of matter extracted from vegetable drugs. arations produced by percolating drugs containing Flavoured syrups contain aromatic or pleasantly both a volatile oil and a resin with an appropriate sol. flavoured substances and are designed to be used as vent (e. . Generally they are prepared by a Syrups process of maceration.g. the marc is pressed. Obsolete dosage forms. The syrup Oleo resins are combinations of volatile oils and exerted an osmotic pressure such that the growth of naturally occurring resins and are generally found by bacteria. page 1019) (Tinctura Quillaiae) (BP 1988. . the expressed liquid is enclosed container for 4 hours. page 1022) Formula: Cardamom oil 3 mL Formula: Caraway oil 10 mL Quillaia liquid extract 50 mL Cinnamon oil 10 mL Ethanol (45%) to 1000 mL Clove oil 10 mL Strong ginger tincture 60 mL Method: Ethanol (90%) to 1000 mL Mix. tincture press. Dose: Dose: 2. 24 hours.5–5 mL. single-screw. percolator is closed.6 mL. sufficient additional solvent to prepare the required volume. 0.16 Aromatic Cardamom Tincture BP (Tinctura Carminative) Example 2. In this process the solid ingredients are three-quarters of the required volume of the finished moistened evenly by sufficient solvent and left in an tincture. 1860s. and the mixture is Example 2. the lower outlet of the to stand and decanting the clear solution.7 Tincture bottle and an enamelled metal. When bined liquids are clarified by filtration or by allowing the liquid is about to drip. sufficient solvent is added to give a shallow layer above the mass.30 | History of compounding Figure 2.12–0. Carminative and flavouring agent. Mix all ingredients together. allow to stand for not less than 12 hours Method: and filter. The percolation process is then allowed to Tinctures can also be produced by a percolation proceed slowly until the percolate measures about process. This damp mass is then added to the percolate and sufficient solvent is added packed into a percolator. Use: Use: An emulsifying agent. by filtration or by allowing to stand and decanting off allowed to macerate in the closed percolator for the clear solution. The marc is pressed.15 Quillaia Tincture BP (BP 1988. Once again the com- is added and the top of the percolator is closed. . Method: Use: Moisten the mixed powders with a sufficient A bitter used to stimulate appetite. in moderately 100 g Carminative and flavouring agent. in moderately 7g Prepare by maceration. Cardamom seed. Obsolete dosage forms. quantity of alcohol (60%).5–2 mL. freshly 12. and used at once Dried bitter orange peel.5 g immediately reduced to removed from the fruit. a moderately coarse immediately bruised and used at once powder.5 g Caraway.17 Compound Cardamom Example 2. Use: Antispasmodic. Add the glycerol and sufficient alcohol (60%) to pro- duce 1000 mL. Dose: 0.18 Compound Gentian Tincture BP (Tinctura Cardamomi Tincture BP (Tinctura Gentianae Composite) (BP 1963. cut small and bruised 100 g removed from the fruit. in moderately 14 g Alcohol (45%) 1000 mL coarse powder Cinnamon. Filter if necessary. page 341) Formula: Formula: Cardamom seed. freshly 14 g Gentian. equipment and methods of preparation | 31 Example 2. in moderately 28 g Method: coarse powder Cochineal. page 140) Composite) (BP 1963. page 1018) 2–5 mL. Example 2.19 Belladonna Tincture Dose: BP (Tinctura Belladonnae) (BP 1988. and prepare 900 mL of tincture by percolation. coarse powder Ethanol (70%) a sufficient quantity Method: Prepare about 900 mL of a tincture by percolation. cut small 37. coarse powder Glycerol 50 mL Dose: Alcohol (60%) sufficient to produce 1000 mL 2–5 mL. Formula: Use: Belladonna Herb. many different formulae being quoted oils or other aromatic substances in water. In products made extemporaneously. Chloroform Water BP (BP 1988. freshly boiled and cooled purified water. some do have a mild therapeutic action. page 1022) Chloroform BP 5 mL Freshly boiled and cooled purified water to 1000 mL Medicated vinegars were solutions of drugs in dilute acetic acid.32 | History of compounding Vinegars (aceta) Waters (aquae) The use of vinegars has now declined but they are Waters are simply an aqueous solution of a volatile worthy of mention as their use as a menstruum for substance and are prepared by aqueous distillation and medicinal preparations dates back to ancient times. Double Strength Chloroform Water BP (BP 1988. bruised 100 g taken by mouth. shaking Chloroform Water BP). Both of these products were prepared by adding sesses antiseptic properties. .6–2 mL. times its volume of freshly boiled and cooled purified page 823) water. present was near to the limit of solubility (chloroform It is worth noting that vinegar (acetic acid) is being is soluble 1 in 200 parts of water). the combined liquids to boiling to coagulate Chloroform Water BP or Double Strength Chlo- expressed cell contents.5 mL Freshly boiled and cooled purified water to 1000 mL A mild expectorant ingredient in cough mixtures. as a simple preservative. The concentrated water is diluted with 39 (Acetum Scillae) (BPC 1973. purpose of a water is to serve as a pleasant flavouring. Double Strength Chloroform Water BP was In the UK there is only one official vinegar remain. allow to stand for not roform Water BP is often added to oral dosage forms less than seven days and filter. Method: a flavouring agent and a preservative. The volatile substance can be Vinegar itself was used as an antiseptic during out. Nowadays aromatic waters are usually prepared from their equivalent concentrated Example 2.20 Squill Vinegar BPC water. breaks of plague. page 1022) Use: Chloroform BP 2. Double Strength Chloroform occasionally. it is added either as Chlo- Macerate the squill with the dilute acetic acid roform Water BP (also referred to as Single Strength in a closed container for seven days. Aromatic waters are saturated solutions of volatile ular in France. which is a good solvent and pos. usually carminative. liquid or gaseous. however. When Squill. hot or cold solution. used currently in burns units to treat Pseudomonas In 1959 Concentrated Chloroform Water BPC was aeruginosa infections in wounds. either solid. developed. Originally. more difficult to prepare as the amount of chloroform ing (Squill Vinegar BPC). it has a pleasant taste and causes a Dilute acetic acid to 1000 mL sensation of warmth. Formula: Chloroform water Chloroform is an anaesthetic when inhaled. water. and vinegars were particularly pop. press the marc and heat Water BP or as Chloroform Spirit BP. Chloroform Water BP and Double Strength Chloroform Water Dose: BP were both prepared using Chloroform BP and 0. Wine and cider vinegar the Chloroform BP to a bottle containing the water were abandoned as a base because of the variations and shaking until the chloroform dissolved in the in composition and quality encountered. Orally it is used as a carminative. The main in the French Codex. strain. equipment and methods of preparation | 33 Concentrated Chloroform Water BPC (BPC 1959. shaking vigorously after each addition.5 mL acceptable to dissolve in a conical measure rather Water BPC 1959: than a glass beaker (see Chapter 6.8 mL. dilution of Concentrated Chloroform Water BPC 1959: Note: This is one of the few times that it is Concentrated Chloroform 2. required volume. Obsolete dosage forms. Chloroform Water BP and Double Chloroform Water BPC 1959 in a 10 mL Strength Chloroform Water BP are often made using conical measure and add to the water.4–0. page 1161) Key Skill 2. page 103). Freshly boiled and to 100 mL cooled purified water Double Strength Chloroform Water BP is A similar method to that outlined in Key Skill 2. . vigorously.1 prepared using a 1 in 20 dilution of Concentrated would be employed in the preparation of Chloroform Chloroform Water BPC 1959 (see Key Skill 2. freshly to 1000 mL boiled and cooled Method: Dissolve the chloroform in the alcohol and add sufficient water in successive small quantities to produce the required volume. 2 Measure 5 mL of Concentrated Nowadays. Stir a concentrate. 3 Make up to volume (100 mL) with more Chloroform Water BP (Single Strength freshly boiled and cooled purified water Chloroform Water BP) is prepared using a 1 in 40 and stir.21 Concentrated Chloroform Water BPC 1959 (Aqua Chloroformi Concentrata) (BPC 1959. Dose: 0. Use: Flavouring and preservative. page 1161) Formula: Chloroform 100 mL Alcohol (90%) 600 mL Purified water.1): Water BP (Single Strength Chloroform Water BP). Concentrated Chloroform Water BPC 1959 5 mL It is worth noting that chloroform preparations Freshly boiled and cooled purified water to 100 mL made using Concentrated Chloroform Water BPC Example 2.1 Method for preparation Chloroform BP 100 mL of Double Strength Chloroform Alcohol (90%) BP: 600 mL Water BP Water to 1000 mL 1 Measure approximately 85–90 mL of The chloroform was dissolved in the alcohol and freshly boiled and cooled purified water in the water added gradually with shaking to produce the a 100 mL conical measure. it should be borne in mind that for certain patients (e. Add 50 g of purified Old pharmaceutical equipment talc and shake.3–1 mL. Add 50 g of purified Other concentrated waters talc and shake. Dose: 0. page 1022) application in liniments and lotions.3–1 mL. form waters include Concentrated Anise Water BP and Concentrated Camphor Water BP. Formula: Anise oil 20 mL Wines (vina) Alcohol (90%) 700 mL Purified water. page 1022) the preparation was made from Chloroform BP and freshly boiled and cooled purified water alone.g. patients on certain types of medication Dissolve the camphor in the alcohol and add and patients who cannot consume alcohol for religious sufficient water in successive small quantities reasons). The ethanol would not be present if Concentrata) (BP 1988.34 | History of compounding 1959 will contain a residual ethanol concentration of about 1. to produce the required volume shaking vigor- ously after each addition. Flavouring. The talc is added to adsorb any Until the advent of the large-scale manufacture of pro- precipitates thereby enabling the production prietary medicines in the twentieth century. Vinum Xericum) or unmedicated (e. Although this Purified water.g.22 Concentrated Anise Use: Water BP (Aqua Anisi Concentrata) A mild analgesic and rubefacient for external (BP 1988. used for compounding activities. heating and condensing. most of the equipment used to establish compounding laboratories was not . with the only difference being the menstruum.23 Concentrated in the Concentrated Chloroform Water BPC 1959 (see Camphor Water BP (Aqua Camphorae Example 2. freshly boiled and cooled to 1000 mL should not normally cause a problem.g. pharmacist required premises that were suitable both for the retail of crude drugs and compounded products Dose: and as a laboratory or preparative area which could be 0. This is due to the presence of alcohol Example 2. sherry) and closely resemble tinc- Method: tures. Use: comminution.21).5% v/v. This Formula: means that although officially the product produced is Camphor 40 g not a BP formula. carminative and mild expectorant. freshly boiled and cooled: to 1000 mL Wines may be either medicated (e. a typical of a bright clear solution. filtration. Before the modern era. The latter needed to be equipped with suitable apparatus for weighing. allow to stand for a few hours Examples of concentrated waters other than chloro. to produce the required volume shaking vigor- ously after each addition. neonates Method: and children. it is widely accepted to be the equiv- Alcohol (90%) 600 mL alent available in pharmacy today. Dissolve the anise oil in the alcohol and add The presence of alcohol in medicated wines makes sufficient water in successive small quantities them more stable than decoctions or infusions. Example 2. allow to stand for a few hours then filter. this may not be a suitable preparation to use. expression. then filter. mixing. (Figures 2. compounding drugs up to the fifteenth century. the troy weights used by silversmiths (ounces divided ogy originally arose in cultures that found the need to into penny-weights) and apothecaries’ weights quantify amounts of precious metals accurately. hence balance) Possibly one of the most famous pharmaceutical inter. The use of troy weights in England was formalised Weighing and measuring by legislation in 1497. which had a movable bal- distilling. blems associated with non-uniformity of weights was Weighing clearly recognised. 225 Oxford Street. Scales of refined. The pro- the earliest times. In addition.8 The Laboratory. 1842. brewing and The portable steelyard. weights and scales in different forms. pivoted fixed beam type. farming. Obsolete dosage forms. These examples clearly illus. square and cylindrical. abandoned for the two-pan (bi-lanx.. For example. painted by J G Murray. of a uniform size or shape and examples are and has been recognised as being of importance since known to be round. weighing more substantial amounts. equipment and methods of preparation | 35 Figure 2. milling.8). The (ounces divided into drachms and scruples) and . when There are many pictures that show typical interiors in London the single-pan (lanx) steelyard beam was of pharmaceutical premises used for compounding. how- a fundamental element of the compounding process ever. London. A balance of this type iors is that depicted in the print of John Bell’s Oxford mounted in a glass case is depicted in a woodcut Street Pharmacy from 1842 (in the Wellcome Museum showing the interior of an alchemist’s laboratory in for the History of Medicine) (Figure 2. and in 1745 the College of It is likely that the development of accurate weighing Physicians commented upon the differences between techniques with the attendant equipment and technol. page 41). thermometers allowed more both of these types were commonly used by those precise control over processes involving heating. who specific pharmaceutical purposes was achieved introduced their use to Western Europe before the time through involvement with alchemy. Another Alkimy the Ordinall by Thomas Norton (1477). and the beam balance suspended on a basic laboratory equipment and techniques for more central pillar were both used by the Etruscans. tions. Some of the development and refinement of ance weight. These weighing methods were adopted by fruits of new scientific discoveries were also applied to the Romans.9 and 2. and many variants of these simple sys- medicines’ compounding processes as they were tems were introduced throughout Europe. John Bell and Co. hand-held types when portability was necessary ratus used in compounding before the modern era. the of Christ. designed specifically for pharmaceutical purposes but Ancient Egyptians. as well as folding trate the wide range and complexity of specialist appa. whereas the avoirdupois weight system was not formally recognised until 1532 (see The accurate weighing and measuring of ingredients is Chapter 3. Com- example is the 1747 engraving of ‘The Chemical pounders of medicines of this period would also have Lab’ (again from the Wellcome Museum for the used larger balances with fixed roof mountings for History of Medicine).10). These weights were not. such as cooking. Assyrians and Babylonians all used originated from other domestic or professional situa. Producing effective.36 | History of compounding Figure 2. until the introduction of graduated glass mea- sures. doxically drugs were allowed to be sold in weights humans have developed increasingly sophisticated measured by the troy or apothecaries’ ounce methods of rendering large particles to a powder. Measuring The measurement of liquids presented another problem to those involved in medicines compounding. Thus although some early gradu- Figure 2. cereals were discovered to be a useful foodstuff. were . In response.9 A pair of hand-scales with box-end beam. accurate liquid measures from opaque materials such as pewter presented problems. The Weights The action of grinding and breaking down substances and Measures Act (1878) further standardised weights has been practised for millennia. 1814–1815. being marked with minims. made by Young and Son. This system continued until metrication (see Simple querns. ated measures were constructed from translucent Rotterdam. A num- ber of archaeological finds indicate that measures made of metal. (480 gr). first used widely in the eighteenth century. horn. silver pans and brass apothecary weights. system. In 1824 the pound in weight was standardised to be 5760 grains (troy) with one pound avoirdupois Comminution being equivalent to 7000 grains troy. No uniform standard volume was accepted. although use of the Roman gallon was wide- spread. Indeed. animal horn and glass were used by those practising pharmacy. ounces or tablespoons (Figure 2. all of the formulae in the 1746 By 1830 graduated glass measures with a lip were Pharmacopoeia were presented in a common troy commonly available. made by Becker and Sons. From the time that by only recognising the pound avoirdupois.10 Chemical scales. certainly in the Roman and Arabic worlds. the College of Physicians adopted sub- divisions of the Roman gallon as the units of liquid measure for the first London Pharmacopoeia of 1618. grocers. as the inscription of graduations inside a measure was difficult to achieve and would be grossly inaccurate and difficult to use. but para.11). most avoirdupois weights generally used by druggists and liquid components would have been weighed. pottery. nineteenth century. basically two abrasive stones moved Chapter 3). against each other to provide a grinding action. 12). nineteenth and twentieth centuries. R. The simple limestone. an early feature of human development. familiar as a universal symbol of phar. etc. composition mortar and pestle. (Left to right) ceramic pill mortar and pestle. stemmed measure in tablespoons and teaspoons. The pestle and (A detection of some faults in unskilful physitians. bell-metal mortar and pestle. equipment and methods of preparation | 37 Figure 2. including marble. to grind spices and aromatic substances. stone mortar with a metal and wooden pestle. 2 fluid ounces. glass or wood. . The Ancient Egyptians and Romans both tages and disadvantages of different materials and the used the pestle and mortar and many examples in a need to reserve different types of pestle and mortar for wide variety of materials are known. mortar combination appeared in a variety of sizes. graduated glass dispensing measure. graduated conical dispensing measure calibrated in liquid grains.11 A selection of dispensing and domestic measures. teenth century. Larger pestles and mortars were generally made Smaller versions were naturally intended to be used on from iron or bronze and were used in larger scale a bench and were generally made from marble. London. a unit rarely used in the UK. certain drug substances was well known by the seven- basalt. The latter were generally quern was refined and became the concave mortar and constructed from lignum vitae and were chiefly used convex pestle. 4 fluid ounces.12 Mortars and pestles. In a text from this period it was The use of the pestle and mortar has been central to described how poisons should not be ground in a mor- compounding activities in the British Isles from Anglo tar for general use and that a glass mortar was most Saxon times and intact examples exist from as early as appropriate for substances to be combined with syrups the beginning of the fourteenth century. (Left to right) horn measure. formed from a wide range of materials (Figure 2. cased minim (drop) measure. iron and bronze. 1651). Recorde. The urinal of Physick. operations for powdering fibrous vegetable drugs Figure 2. Obsolete dosage forms. The advan- macy today. be easily handled. rollers and pestle suspended from an overhead beam.13 A selection of spatulas. iron and steel in a variety patients. cal equipment can be found elsewhere in this chapter. specific functions for compounding ingredients which are now rarely seen. Old pharmaceutical containers tars under the action of acids. The pharmacist prepared sufficient phials for the required number of doses and directions Descriptions of many other types of old pharmaceuti- were written on a label tied to the neck of the phial. which was to find a suitable container in which to present the ideal for forming both pestles and mortars. shapes and degrees of flexibility. They come times as a method to present liquid preparations to in wood.13). pill machine and pill counter (page 27) Problems encountered with these early examples * plaster iron (page 28) of pestles and mortars included the shedding of parti. horn. pill rounder. pill container. pill roller.38 | History of compounding and caked chemicals. tile founders using the same techniques as employed to with graduated scale. Some mortars could be very * decoction apparatus (page 20) large by today’s standards and needed to be mounted * infusion pots and mugs (page 23) on their own wooden support with the corresponding * lozenge containers. lozenge board. bronze. pill cutter. pill spatula. The great ceramic tech- nologist Josiah Wedgwood solved these problems by A major concern of the compounders of medicines was developing ‘biscuit porcelain’ in the 1770s. Often mor. pill pestle. . Phials were made in shapes. * tincture bottles and tincture press (page 30). cutters (page 26) tars were of such a size that they were cast by bell * pill mortar. medicines during the sixteenth and seventeenth centu- ries. and the practice continued well into the nine- Other old pharmaceutical equipment teenth century. The use of finished product to the patient in a form that could this material was widespread by the nineteenth cen. cles following pulverisation of drugs in a metal mortar and the dissolution of limestone and other stone mor. make bells. * bougie moulds (page 18) These have been catalogued by W A Thorpe in his book * cachet sealing equipment (page 19) English Glassware in the 17th Century. while retaining pharmaceutical effi- tury and pestles and mortars from this period are often cacy. Catalogue of Figure 2. and examples most common method of presenting compounded exist from all eras since the Roman period (Figure 2. Equipment for the manipulation of formulations Glass phials Spatulas used to manipulate formulations have been The glass phial has certainly been used since Roman made in a variety of forms for centuries. sizes and colours char- Some examples are: acteristic of the period in which they were produced. There is a wide range of stock containers with referred to as ‘Wedgwood mortars’. bone. The unit dose round phial was probably the of sizes. of the nineteenth century. these were hand-made and indi.16). When first produced.5 cm tall. Naturally. . London. either a metal lid or a cover made of parchment tied at mated production commencing in the 1920s. Obsolete dosage forms.5 cm with a slight taper. These were superseded in the later seventeenth and eighteenth centuries by lighter coloured. 2. and 7. Variants in the six- teenth and seventeenth centuries were cylindrical but still of dark green glass. Those from the six- teenth century were generally made of dark green glass up to 12. with fully auto.15 and Figure 2.5 cm high or pear-shaped bottles between 5 twentieth centuries. These the neck of the jar. equipment and methods of preparation | 39 Old English Glass (Churchill. bottle rendered distinguishable by touch. solid and semi-solid preparations were traditionally vidually blown into a flat iron mould. The Pharmacy Act of 1868 secured the future for this type of container by effectively Medicine bottles and containers empowering the Pharmaceutical Society to regulate Medicine bottles for oral and external liquids only the keeping. duations indicated by moulded protrusions on the side Glazed jars made of porcelain. During the sixteenth and seventeenth centuries. dispensing and selling of poisons in a came into common use in the early part of the nine. Special poisons’ bottles were introduced from around 1859 when the idea for the sharply contoured hexagonal or octagonal bottle with vertical or diagonal fluting discernible by feel was patented by John Savory Figure 2. an oxymel. their medications in decorated Delft pottery jars. the twentieth century semi-automated production of This type of jar was generally glazed and sealed with glass medicines bottles had begun. two Figure 2. machine-produced bottles often had dosage gra.14.16 Octagonal bottle embossed with dosage marks extracts and a confection. and R W Barker.5 and 7. 1937).5 cm tall and had a wide base tapering in a steeple shape to a narrow neck. nineteenth and around 7. In the seventeenth century and beyond the phial began to be produced in thinner glass of a lighter colour in an oval or globular shape.5 cm tall. stoneware or earth- of the bottle. late nineteenth century. a medicinal wine. In the early fifteenth century phials were generally between 5 and 12. More affluent patients received later. mould-blown cylinders Figure 2. teenth century (Figures 2. bottles from these periods enware with lids were mass produced from the middle were generally sealed with a cork stopper. of 1–6 ounces.14 A selection of nineteenth and twentieth century medical preparations. In the middle of the eighteenth century white glass phials were introduced.15 Typical pharmacy bottles. By the start of supplied in pottery jars between 2. in particular. probably gained greater recognition latterly as a dec- Emulsion and viscous liquid bottles orative item. Bulk liquid containers Specially designed glass stock bottles with specific Figure 2. functions were commonplace in the nineteenth century. In this case the stopper was designed to fit only loosely in the neck of the bottle. These came in a variety of sizes for different purposes. The latter was probably introduced by Corbyn. which prevented debris sticking to the top of the bottle while in storage. Stacy and Co. The swan-necked carboy has Figure 2. The whole neck and stop- per assembly was further protected by a removable glass dome dust cover.18 Swan-necked carboy.17 Collection of carboys.17 and 2. Oil bottles Oil bottles had a funnel-shaped neck which flared out from the shoulder of the bottle. The demijohn. Other bulk liquid containers Two commonplace standard stock bottles for bulk liquids were the Winchester quart bottle. and the Corbyn quart bottle of 40 oz capacity. and more notably the carboy. resting on a flange around the stopper. emulsions. The close-fitting ground glass stopper was grooved on one side. nineteenth century. The chip box was produced on a mass scale by the 1840s. the stopper was not tight enough to allow drying sugar crusts to cause the stopper to become stuck. which was of 80 oz capacity. which was gener- ally a round or oval box constructed from hand-cut shavings of wood. Thus. are other examples of large-volume containers principally constructed from glass. but was superseded by card- board boxes lined with impervious greaseproof paper. of London. Syrup bottles Bottles designed to contain stock syrups were also made with a flared neck.18). pounding (Figures 2. which allowed excess oil to drain from the stopper back down into the stock bottle. and is instantly recognisable as a symbol Wide-mouthed glass containers were used to store and representing pharmacy and pharmaceutical com- supply viscous liquids and.40 | History of compounding An alternative container for topical preparations and some solid unit dose oral forms used since the fifteenth century was the ‘chip box’. although dust and debris was excluded and the fit of the flanged top to the neck was sufficiently good to prevent evap- oration. . When symbols were used. metrication.g. tem) was introduced for bulk counter sales and was tant that compounders are aware of older weighing based on an imperial pound of 7000 grains. * 1 fluid ounce of water weighs 1 ounce ing formulae. drachms (pronounced Unit one could also be expressed as ‘j’ (e. fluid ounces In accordance with current weights and measures (fl oz) and pints (pt) were all multiples thereof (see regulations it is illegal to use the apothecaries’ or impe. Further systems as. Scruples. whether from official texts or as a result (avoirdupois). tionship between these units and grains is shown ceivable that some old formulae may still be encoun. These old systems of measuring and Volumes weighing were called the ‘apothecaries’ system’ and Within the imperial system. For example: Apothecaries' weights i ¼ 1 drachm Historically. will need at * 110 minims of water weigh approximately 100 least a rudimentary understanding of the process of grains. . Fluid drachm (fl dr). The rela- be expressed using the metric system. rial systems when dispensing prescriptions. it is not incon. iij ¼ iii).1). of barley) and formed the base unit of the apothecaries’ system.5. tered today. these are not the only The imperial system (also called the avoirdupois sys- systems that have been used historically. The different abbreviations and symbols histori- cally used in pharmacy and their meanings are Metrication summarised Tables 3.g. the figures were written in Roman numerals after Weights the symbol. Unfortun- ately. a number of older formulae were never updated The relationship between weights and volumes and anyone looking at old extemporaneous dispens. j ¼ i).3 Historical weights and measures Metrication 41 Weights 41 Although all modern pharmaceutical formulae are Imperial weights (avoirdupois) expressed in grams and litres. although most formulae encountered will units of avoirdupois ounces were also used. multiples thereof (see Table 3. only the final one was expressed by ‘j’ (e. dard unit of volume. Table 3. in Table 3.2. It is impor.3).4 and 3. grains (gr) were the standard unit of iii ¼ 3 drachms weight (originally based on the weight of one grain iv ¼ 4 apothecaries’ ounces. ‘drams’) and apothecaries’ (or troy) ounces were all but where two or more units were expressed together. minims (m) were the stan- the ‘imperial system’. of examining old prescription books. 2 pt ¼ 2 pints drachms.g. 1 grain becomes . 2 dr ¼ 2 drachms fl dr Fluid drachm e.42 | History of compounding Table 3. scruples Table 3. avoirdupois ounces and avoirdupois pounds fl oz Fluid ounce e. 2 oz ¼ 2 ounces (avoirdupois) (avoirdupois) 7000 16 1 lb Pound e.g. 2 oz ¼ 2 ounces ounces pounds (apothecaries') (apoth) (apothecaries') ¼ 960 grains 437. For example.g. 2 fl dr ¼ 2 fluid drachms Table 3. fluid pt Pint e. 60 m) ¼ i ss ¼ fs ¼ 1/2 dr or 1/2 fl dr ss ¼ fs ¼ 1/2 fl oz 1 =8 fluid ounce (1=8 fl oz) ¼ i iss ¼ ifs ¼ 11/2 dr or 11/2 fl dr. 10 gr ¼ 10 grains 20 1 or gr x ¼ 10 grains 60 3 1 m or min Minim e.5 1 oz Ounce e.g.g.4 Historical weighing and measuring units and apothecaries' (troy) ounces and symbols used in pharmacy Grains Scruples Drachms Apothecaries' Symbol Meaning Example or troy ounces gr Grain e.g.g.3 Relationship between minims. the numerical answers 480 minims ¼ i prove to be unwieldy to calculate and difficult. fluid ounces and pints Minims Fluid drachms Fluid ounces Pints 60 1 Table 3.2 Relationship between grains.1 Relationship between grains.g. Teaspoonful.g. if not Scruple impossible. 2 lb ¼ 2 pounds (imperial) (imperial) Table 3. it would 480 grains ¼ i appear that simple calculation should result in the desired conversion. metricated to a 5 mL dose ¼ i Conversion between apothecaries'/imperial Apothecaries' (troy) ounce and metric systems As exact scientific equivalents of the weights and mea. 2 fl oz ¼ 2 fluid ounces Grains Avoirdupois Avoirdupois oz (apoth) Ounce e. For Fluid drachm (fl dr) by volume example: 60 minims (60 min. to handle. 10 m ¼ 10 minims 480 24 8 1 dr Drachm e.5 The meaning of different historical 480 8 1 symbols used in pharmacy 9600 160 20 1 Symbol Meaning Drachm (dr) by weight ‘Half’ was expressed either by ss or fs. Fluid ounce (fl oz) sures in the systems are readily available. However. 10 minims or 1 ounce ðavoirdupoisÞ 80 10 shall be equivalent to 2% 96 a 12 100 500 a a Therefore a formula for imperial quantities is Above Above9696doses dosesdispense dispense500 500mL mLplus plusthe themetric metricvolume volumeopposite opposite metricated by converting each quantity into a the balance the ofof balance doses. elixirs. Any (obsolete dose volume 60 m) existing formulae were thus converted to these new dose volumes. . In imperial/avoirdupois systems.6 Dose and quantities table.e. formulae are metricated on the basis that: 40 5 40 200 8 9 8 9 48 6 > < 10 grains > = > < 1 fluid ounce > = or in or 1 ounce ðapothecaries0 Þ 64 8 60 300 > : > . linctuses. Historical weights and measures | 43 0.064 79 grams. Imperial doses of oral liquid medicines in Table 3. etc. 24 3 Therefore. Dose volume 5 mL between a dessertspoonful and a tablespoonful).6).6. Bulk quantities are adjusted to suitable metric ing. A more rational method of metrica. tion. when the compounding process was cedure the formula must be adjusted to show the com- metricated it was considered to be the ideal opportu- position of each dose. In order to minimise this problem. The quantity of each ingredient nity to improve the system of dose measurement used per dose is then metricated using the information by the patient. but to achieve 1 4 /2 5 25 the necessary adjustments and compromises. a practice quite common in the treatment of infants.e. were measured using ordinary domestic spoons. doses. It was considered more sensible to adopt a system equivalents (see Table 3. calculated. The number of metric doses and hence the Owing to considerable variation in the design of quantity of preparation to be dispensed is also deter- spoons. percentage concentration using the above approxima- tion was adopted when it was introduced to dispens. In the metrication pro- In addition.6. this was a serious cause of error which could mined by reference to Table 3. i. a dessertspoonful (2 upon and the number of doses originally prescribed is fluid drachms) and a tablespoonful (1/2 fluid ounce). 1 12 1 /2 External preparations 16 2 20 100 The activity of pharmaceutical preparations is gov- erned by the concentration of active ingredients. of metrication in which well-judged ‘rounding off’ Oral preparations would result in convenient quantities without preju- In oral preparations activity is governed by the amount dice to the patient’s treatment. the number of addition. of active ingredient per dose. it was decided to standardise on two dose doses and the total quantities in the metric system volumes. Prescribed 1 To be dispensed 2 For these reasons the metrication process adopted Number of Imperial Number of Metric by law (Weights and Measures Act 1970) was doses volume fl oz doses volume mL designed not to be scientifically exact. It must be emphasised that this is the only metrication process 8 1 10 50 which may be used legally when compounding. Where doses that doses should be measured using a standard 5 mL and total quantities are ordered in apothecaries'/ spoon and that whole spoonfuls were to be used. > : > . i. it was decided Table 3. be further exacerbated when fractions of spoonfuls were used. A 5 mL dose for children (about one and a in column 2 shall be dispensed half teaspoons) and a 10 mL dose for adults (midway (A) Paediatric mixtures. a The metric dose volume to be adopted is decided teaspoonful (1 fluid drachm). for external preparations a simple method 32 4 30 150 of metrication could be adopted. Because of this anomaly.6A and supply and measures from imperial to metric (Tables 3. conver- The quantity order is in fluid ounces but the sion of emulsions follows the directions for external dose is expressed in fluid drachms. The dose for emulsions such as Liquid Paraffin Emulsion BPC Simple Linctus BP was usually 1 to 4 fluid drachms (8 to 30 millilitres). It was impossible to standardise the dose to a 5 or 10 mL Mitte vi standard as with other oral liquid dosage forms because Sig i tid of the importance of the ratio of oil:water:gum in pre- paring a stable primary emulsion (see Chapter 8. enabling dose to fluid ounces: the conversion to be based on the final volume rather 1 fl dr = 1/8 fl oz than the individual dose volume.6C). i. doses. etc.8). Although in most cases metrication of oral formu- Example 3.6B is used. therefore refer to Table 3.dispense dispense 500 500mL mL plus the metric metric volume volumeopposite opposite volume opposite the balance of the volume. Convert the and bulk oral preparations (see Table 3. pages Answer: 132 and 134 for further details on the preparation of a primary emulsion). it is therefore pos- 6/(1/8) = 48 doses. elixirs.44 | History of compounding (B) Mixture. The metric equivalent of i is sible to produce summary conversion tables of weights 5 mL. Dose volume 10 mL (obsolete dose (C) External and bulk oral preparations solids/liquids volume 1/2 fl oz) Prescribed 1 To be dispensed 2 Prescribed 1 To be dispensed 2 Wt/vol (av/imp) oz/fl oz Wt/vol (metric) g/mL Number of Imperial Number of Metric 1 doses volume fl oz doses volume mL /2 10 1 1 /2 1 10 1 25 2 1 2 20 11/2 50 4 2 2 5 50 6 3 3 8 4 4 100 10 100 12 6 5 16 8 6 200 20 10 8 20 200 24 12 10 300 32 16 12 30 300 40 20 16c 500 48b 24 50 500 20 fl oz c b b Above 16 oz (1 lb) and 20 fl oz (1 pint) dispense 500 mL plus the metric Above48 Above 48doses. Using the principles outlined above. these tables are to be used as a guide only. emulsions pro- preparation vided a problem owing to their formulation. linctuses. It should be borne in mind that owing to the round- terms of fs (10 mL dose) Table 3. the the balance balance ofof doses. doses. ing applied. If the dose is expressed in 3.e. Conversion tables for ingredients Calculate the number of doses ordered.7 and 40 5 mL = 200 mL.1 Prepare the following lae was a fairly straightforward process. . 5 41=2 . 1/150 0.15 1 =3 20 21–25 1. Historical weights and measures | 45 Table 3.5 14–16 1 1/500. 1/75 0. 1/300 0. 1/480 0.3 1/160. 10 600 181–190 12 1/8 7.5 1/80. 1/24 2. 71=2 450 151–165 10 1/12 5 8 500 166–180 11 1/10 6 9.3 3 =5 40 34–37 2. 6 400 136–150 9 1/15 4 61=2 .7 Summary conversion table for weights from grains to milligrams or grams Grains Milligrams Grains Milligrams Grains Grams 1/600 0.5 11–13 800 191–220 13 1/6 10 221–250 15 251–275 17 276–325 20 326–350 22 351–375 23 376–400 25 401–425 26 426–450 28 451–510 30 .6 11=4 75 52–57 3.5 1/50 1. 5 300 116–135 8 1/20 3 51=2 .5 1/320.2 2 =5 25 26–29 1.25 1 =2 30 30–33 2 1/200 0.8 1/240 0.8 11=2 100 58–65 4 1/60 1 2 125 66–76 4.2 1/400 0.25 21=2 150 77–84 5 1/40 1. 1/120 0.5 3 200 85–102 6 1/30 2 31=2 .5 1 60 44–51 3 1/100 0.125 1 =4 15 17–20 1.5 1/130.1 1 =5 12.4 3 =4 50 38–43 2. 4 250 103–115 7 1/25. 9 251–275 15 17–18 1 276–300 17 19–22 1.2 111–130 7 4–41/2 0.12 75–84 4.06 56–64 3.5 1 2 /2 0.15 85–93 5 3 0.46 | History of compounding Table 3.8 Summary conversion table for volumes from minims to millilitres Minims Millilitres Minims Millilitres 1 0.7 221–250 14 14–16 0.8 371–400 22 33–37 2 401–450 25 38–46 2.5 11/2 0.2 301–330 18 23–27 1.6 201–220 12 12–13 0.5 331–370 20 28–32 1.5 186–200 11 10–11 0.3 150–167 9 6–71/2 0.18 94–110 6 31/2 0.4 168–185 10 8–9 0.09 65–74 4 2 0.25 131–149 8 5–51/2 0.5 451–500 28 47–55 3 . PART 2 Pharmaceutical forms and their preparation . . 4 Key formulation skills Weights and measures 49 Millimoles 59 Weighing 49 Milliequivalents and equivalent weights 60 Balances 50 Isotonicity 60 Measuring 55 Percentage strength 61 Measures 56 Parts and solubility 61 Medication strength 59 Dilutions 63 It is necessary to master a number of key formulation Table 4.1 Main weighing units used in pharmacy skills in order to be able to produce accurate and effica- cious extemporaneous preparations. This chapter out- Unit Abbreviation Gram equivalent lines the key basic concepts and calculations that will be used throughout this book. All practitioners, irrespective 1 kilogram 1 kg 1000 g of their own individual area of practice, must become 1 gram 1g 1g competent in the key skills outlined in this chapter. 1 milligram 1 mg 0.001 g Weights and measures 1 microgram 1 mg (or 1 mcg) 0.000 001 g 1 nanogram 1 ng 0.000 000 001 g Weighing and measuring are possibly the two most fundamental practical skills practised by a com- pounder. During compounding, ingredients will need For weights less than 1 mg, the units of the weight to be either weighed or measured and the accuracy of are usually written in full (for example 1 nanogram the compounder’s technique will have a great bearing rather than 1 ng, or 3.4 micrograms rather than on the accuracy and efficacy of the final product. 3.4 mg). This is because the first letter of the abbrevi- ation (the m or n) when written by hand may be mis- Weighing taken for the letter ‘m’. This could then result in dosing When weighing pharmaceutical substances, the Systeme errors of one-thousand times plus. International d’Unites (SI) based around the gram (g), Conversions between the main weighing units are is the system that is used. Variants on the base unit are essentially easy as they are all based around 1000 times formed by 1000 times increases or divisions of the multiplications or divisions of the base unit. However, gram. Table 4.1 summarises the main units used care must be exercised in carrying out these calcula- within the pharmaceutical profession. tions as errors may not be immediately obvious. 50 | Pharmaceutical forms and their preparation Balances Example 4.1 Convert 2.3 g into When weighing a pharmaceutical ingredient or product, milligrams it is important to select the correct balance. Different To convert from grams to milligrams, multiply types of balance are designed to weigh within different by 1000: weight ranges to differing degrees of accuracy. For 2:3 1000 ¼ 2300 milligrams example, a balance designed to weigh 5 kg to an accuracy of 0.01 kg (10 g) is not going to be suitable to weigh 200 mg (0.2 g). Broadly speaking, there are likely to be three dif- Example 4.2 Convert 7894 ferent types of balance that will be encountered in a milligrams into grams pharmaceutical environment. These are: To convert from milligrams to grams, divide by * the Class II balance or electronic equivalent 1000. * sensitive electronic balances 7894 / 1000 ¼ 7:894 g * balances for weights greater than 50 g. All balances have different accuracies, precisions and tolerances and it is important that the correct balance Example 4.3 Convert 3.2 nanograms is used for a particular weighing task. In order to select into milligrams the correct balance for a particular weighing task, the accuracy, precision and tolerance of the balance Using the table illustrated in Key Skill 4.1, need to be taken into consideration. Although often attempt the calculation in stages. First convert misunderstood and interchanged, there are key differ- from nanograms to micrograms: ences between these three terms: 3:2 / 1000 ¼ 0:0032 micrograms * Accuracy – is a measure of the capability of a Then convert from micrograms to balance to approach a true or absolute value. milligrams: * Precision – is the relative degree of repeatability, 0:0032 / 1000 ¼ 0:000 003 2 milligrams i.e. how closely the values within a series of replicate measurements agree. Key Skill 4.1 Conversion between base weight units To convert between the base weight units, multiply or divide the figure by 1000. For conversions between more than one base unit (e.g. nanograms to grams), convert via any intermediate units (e.g. micrograms and milligrams). Conversion from kilograms to nanograms Conversion from nanograms to kilograms 1 kilogram 1 nanogram 1000 1000 1 gram 1 microgram 1000 1000 1 milligram 1 milligram 1000 1000 1 microgram 1 gram 1000 1000 1 nanogram 1 kilogram Key formulation skills | 51 * Tolerance – or ‘limits of permissible errors’ is the Table 4.2 Traditional balance capabilities extreme value of an error permitted by specifications for a measuring instrument. Balance type Minimum Increment Normal weighable weight maximum quantity weighable Standard dispensing balances quantity The balance most commonly found in pharmacies will be either a traditional ‘Class II’ dispensing beam bal- Class A 50 mg 1 mg 1g ance or a modern electronic equivalent. Class II bal- Class B 100 mg (see 10 mg 50 g ances are similar to older Class B balances and use the below) same weighing techniques. Class C 1g 100 mg 2 kg Class B balances Class B beam balances were traditionally used in phar- macies before the introduction of Class II beam bal- Class II balances ances (and later, electronic balances). The Weights and Class I–IV balances arose from legislation introduced Measures Regulations (1963) categorised weighing in the 1980s to harmonise the laws of the European instruments for certain retail transactions into three Economy Community (EEC) member states that different categories: Class A, Class B or Class C. The related to non-automatic weighing instruments Class B balance (Figure 4.1) was the balance most (Weights and Measures Act (1985)). This legislation commonly found in pharmacies, with Class A balances replaced the older classification of balances under being reserved for weighing amounts below the limits which a dispensing-type beam balance was Class B of a Class B balance. The weighing capabilities of the (see above). They are stamped with both a maximum three different types of balance are summarised in and a minimum weighable quantity and so it is easier Table 4.2. to identify whether a balance is suitable for a particu- As outlined in Table 4.2, Class B beam balances lar task. A traditional Class II dispensing beam balance were designed to weigh up to 50 g in 10 mg increments. (Figure 4.2) is marked with a maximum weighable They had a nominal minimum weighable quantity of quantity of 25 g and a minimum weighable quantity 100 mg, but in practice a higher limit was preferred for of 100 mg and, as with Class B balances, Class II potent substances (e.g. 150 mg). balances typically have an increment weight of Figure 4.1 Class B balance. 52 | Pharmaceutical forms and their preparation Figure 4.2 Class II balance. 10 mg. As was the case with the older Class B balances, 1 Obtain the ingredient to be weighed and fill in the in practice many pharmacists chose to adopt a higher batch number on the product worksheet (see limit for potent substances (e.g. 150 mg). Chapter 5, Figure 5.1). 2 Using a set of dedicated tweezers, place the Weighing techniques for Class B and Class II correct weights on the metal scale pan (on the left- dispensing beam balances hand side). Weights should be handled as little as The same weighing technique is used for both Class B possible. This prevents the transfer of particles or and Class II dispensing beam balances. Within this grease from your hands onto the weights, which section, the term ‘Class II’ will be used (as this is the would alter their weight. Always use the least more modern balance) but the same techniques will number of weights possible, as this will reduce apply to the use of Class B dispensing beam balances. error (each individual weight has its own Before use, the balance must be set up at a partic- accuracy). Note that when weights are added to ular location. This should ideally be on a solid, level, the scale pan, the pointer will deflect to one side. firm surface. In order to ensure that the balance is 3 Close the weights drawer before weighing. If the exactly level, a multidirectional circular spirit level drawer is left open, powder or other ingredients should be used, centralising a bubble contained within may fall into the drawer and adhere to the the level in the central circle. Once the balance has weights, altering their weight. been set up at a particular location, it is important that 4 Transfer the ingredient to the glass pan using a it is not moved while in use as this will affect the spatula, until the pointer is central. Ensure when accuracy of the instrument. reading the pointer that you move to align your Next check that the scale pans are clean and that eye with the scale to avoid any parallax errors (see the pointer is in the centre of the scale. If the pointer is Figures 4.4 and 4.5). not in the centre, centralise by referring to the instruc- 5 Check the weight, the name of the ingredient, and tions for that particular model. then initial the worksheet. When using the balance, the weights (which are to 6 Ask for a second, independent check of your be found in the balance drawer) are placed on the weight from another member of staff, who will metal pan (on the left), and any ingredient being also initial the worksheet. weighed is placed on the glass pan (on the right). The following general method should be followed In some situations you may be working on your own when using a Class II balance: (for example if preparing an emergency preparation Key formulation skills | 53 outside of normal hours). On these occasions you must weighing more than one ingredient, once weighed, perform your own second check in point 6 above. place each ingredient on a piece of labelled paper on the bench. If you are weighing a greasy product, place a piece Example 4.4 Weighing 10 g of Zinc of greaseproof paper on the glass scale pan. Remember Oxide BP powder on a Class II to counterbalance this piece of paper with a piece of dispensing beam balance the same weight on the other side. Check the pointer is still in the middle when the greaseproof paper is on 1 Check that the balance is clean and dry and both sides. Ensure that both pans can move freely and that the pointer is in the centre of the scale. that the paper is not touching the sides of the balance 2 Obtain the stock pot from the shelf and or bench. If the pan’s movement is hindered by the write the batch number (the number on paper touching the side, the balance will not weigh the label after BN or LOT) in the table on accurately. the product worksheet. 3 Place a 10 g weight on the metal scale pan. 4 Using a spatula, transfer 10 g of Zinc Example 4.5 Weighing 10 g of Simple Oxide BP onto the glass scale pan. Check Ointment BP on a Class II dispensing that the pointer is in the centre, check the beam balance ingredient and sign your initials in the ‘Dispensed by’ box. 1 Check that the balance is clean and dry and 5 Ask for a second check from another that the pointer is in the centre of the scale. member of staff. Once the check has been 2 Place a piece of greaseproof paper on the performed, the member of staff initials the glass scale pan. ‘Checked by’ box. 3 Counterbalance the greaseproof paper with 6 Return the stock pot to the shelf. a second piece on the metal pan. Check the pointer is in the centre of the scale. Extract from the product worksheet: 4 Obtain the stock pot from the shelf and write the batch number (the number on Ingredient Batch Quantity Dispensed Checked the label after BN or LOT) in the table on number by by the product worksheet. Zinc Oxide BP 10 g 5 Place a 10 g weight on the metal scale pan. 6 Using a spatula, transfer 10 g of Simple Ointment BP onto the greaseproof paper Although most Class II balances contain a gradu- on the glass scale pan. Check that the ated scale within the pointer window (usually expressed pointer is in the centre, check the in either milligrams (mg) or grains (gr) for some Class B ingredient and sign your initials in the balances), it is best to weigh an ingredient using the ‘Dispensed by’ box. method outlined above (i.e. by placing weights equal 7 Ask for a second check from another to the target weight on one scale pan and counterbalan- member of staff. Once the check has been cing with the appropriate amount of solid or liquid until performed, the member of staff initials the the pointer registers zero in the centre of the scale). ‘Checked by’ box. Although useful as a guide, it is not advisable to use 8 Return the stock pot to the shelf. the scale to accurately indicate the weight of solid or liquid on a balance, as although the central point can be Extract from product worksheet: read easily without any parallax error, the reading Ingredient Batch Quantity Dispensed Checked of graduations at either side of the central point will number by by be more difficult because of the angles involved. Simple 10 g Before weighing any ingredient, the product for- Ointment BP mula should be written out in full, in ink. If you are 54 | Pharmaceutical forms and their preparation When weighing a material that can stain (e.g. If the quantity of an ingredient to be incorporated Potassium Permanganate BP), remember to place a into a product is quoted in grams (or other unit of piece of paper under the weighing pan and push a large weight, e.g. mg), it will be necessary to weigh the liquid piece of paper up to (not underneath) the balance. This ingredient rather than measuring it by volume. Any liq- will catch any material that falls off the balance pan uid can be weighed on a Class II dispensing beam balance during weighing and will avoid the bench and balance by measuring into a small pot. Remember to counter- becoming stained. balance the pot first (check the pointer is in the centre). Electronic pharmacy balances Unlike the Class II dispensing beam balance, the scale Example 4.6 Weighing 5 g of Syrup BP pan on an electronic balance is usually made of metal on a Class II dispensing beam balance rather than glass. This means that the ingredient to be 1 Check that the balance is clean and dry weighed is not placed directly onto the scale pan. and that the pointer is in the centre of the Solids are weighed onto a watch glass, greasy solids scale. onto greaseproof paper and liquids into a small pot. In 2 Place a small pot on the glass scale pan. all three cases, tare the balance (i.e. set the electronic 3 Counterbalance the pot with a second pot display back to zero) with the container for the ingre- on the metal pan. Check the pointer is in dient (e.g. watch glass, greaseproof paper, etc.) on the the centre of the scale. balance beforehand. Taring the balance with the ingre- 4 Obtain the stock pot from the shelf and dient container on the balance will ensure that only the write the batch number (the number on weight of the ingredient placed in the container will the label after BN or LOT) in the table on register on the display. By using this method, the pro- the product worksheet. cedure of subtracting the weight of the container from 5 Place a 5 g weight on the metal scale pan. the display weight is avoided, making the weighing 6 Pour an amount of Syrup BP into a beaker process easier and less susceptible to error. to use as stock. Once an ingredient is Sensitive electronic balances removed from its stock container it should If the amount of substance to be weighed is less than not be returned, to reduce the risk of 150 mg, it would not be appropriate to weigh the contaminating the stock liquid. For this ingredient on a standard dispensing balance, such as reason, avoid transferring too much as a Class II balance, as the accuracy of the balance would this is wasteful. make the error too large. Clearly, the smaller the 7 Transfer 5 g of Syrup BP from the beaker amount to be weighed, the bigger the inaccuracy as a into the pot on the glass scale pan. Check percentage of the total weight becomes. that the pointer is in the centre, check the For example, measuring 200 mg on a Class II bal- ingredient and sign your initials in the ance would result in 200 mg 10 mg (i.e. 5%). ‘Dispensed by’ box. When the weight to be measured is reduced to 8 Ask for a second check from another 100 mg (i.e. 100 mg 10 mg) this increases the per- member of staff. Once the check has been centage inaccuracy to 10%. Further reductions in performed, the member of staff initials the the amount to be weighed would further increase this ‘Checked by’ box. percentage inaccuracy. 9 Return the stock pot to the shelf. To weigh amounts below 150 mg, it is usual to use a more sensitive electronic balance. These typically Extract from product worksheet: have an accuracy of 1 mg (10 times more accurate Ingredient Batch Quantity Dispensed Checked than the common pharmacy balance). The typical number by by minimum amounts that are weighed on these balances Syrup BP 5g are 50 mg for non-potent substances, increasing to 100 mg for potent substances. 3). although they can vary dramatically and you must become familiar with the tolerances of the individual balance(s) that you encounter. All balances will have an inherent accuracy that will affect your confidence in the final product. it will be necessary to by hand may be mistaken for the letter ‘m’. it is also best practice when referring to product that is less than the minimum recommended volumes in multiples of litres to write the word ‘litre’ Key Skill 4. The final type of balance that you are likely to find 3 Place a watch glass onto the balance and in a pharmacy are the balances designed to weigh tare. Large balance 50 g and upwards Variable Variable 2. Type of balance Typical minimum weight Typical maximum weight Typical accuracy 1. Check the ingredients.2 Determining the appropriate balance for use It is important when weighing any ingredient that consideration is given to the accuracy of the instrument in use. of 10 cm would occupy. Although staff. This is because the first letter of the abbreviation (the m) when written In some circumstances. Remember that there are three main types of balance used in pharmacy and it is important to check the accuracy of each balance that you use. weight. incorporate an amount of active ingredient into a Furthermore. Once the check has been performed.e. A litre is defined as one cubic decimetre ‘Checked by’ box. Sensitive electronic balance 50 mg (non-potent) 100–500 g 1 mg 100 mg (potent) . As described for weights above. In these circum- Example 4. i. Using the wrong balance is in some cases as bad as weighing the wrong amount. (0. check the ingredient and sign your initials in the ‘Dispensed by’ box. transfer 10 g of Zinc These balances will be used to measure out bulk Oxide BP to the watch glass. 25 g) of a Class II balance or electronic equivalent. how this is achieved and when it is appropriate will 2 Obtain the stock pot from the shelf and be given within the respective product chapters. Typical balance ranges are detailed below. there are a number Extract from product worksheet: of different volumes based around the litre that are in Ingredient Batch Quantity Dispensed Checked common use in pharmacy today (Table 4. Key formulation skills | 55 weighable quantity of a balance. it is necessary to weigh a known excess of Oxide BP on an electronic balance active ingredient and then dilute further during the compounding procedure.7 Weigh 10 g of Zinc stances. write the batch number (the number on the label after BN or LOT) in the table on Balances for weights greater than 50 g the product worksheet.001 m3). Class II dispensing balance or 150 mg 25 g 10 mg electronic equivalent 3. Further explanation of 1 Check that the balance is clean and dry. Measuring 6 Ask for a second check from a member of Liquids are universally measured in litres. weights over the maximum weighable weight (i. 4 Check the display is reading zero. the litre is commonly the member of staff will initial the used. 5 Using a spatula. not part of the SI system of units. for volumes less than 1 mL the Zinc Oxide BP 10 g units of the volume are usually written in full (for example 1 microlitre rather than 1 mL).e. In a sim- number by by ilar way to weights. the volume that a cube with equal sides 7 Return the stock pot to the shelf. 7 litres into There are two main types of vessel used within millilitres pharmacy for measuring liquids: To convert from litres to millilitres. millilitres). Converting between the main volume units is as important as mastering the conversions between weight units. For conversions between more than one base unit (e. convert via any intermediate units (e.56 | Pharmaceutical forms and their preparation Table 4. This will assist in reducing any con. Key Skill 4. Example 4. attempt the calculation in stages. As with weight conversions.10 Convert 5. Conversion from litres to microlitres Conversion from microlitres to litres 1 litre 1 microlitre 1000 1000 1 millilitre 1 millilitre 1000 1000 1 microlitre 1 litre . ð5:5 10 6 Þ fusion with the unit ‘one’ (‘1’). To convert from millilitres to litres.3. Conical measures Example 4. pipettes are also used in the prep- aration of some pharmaceutical products. Measures versions are easy as they are all based around 1000 Any vessel that is used to measure accurately an ingre- times multiplications or divisions of the base unit. conical measures rather than cylindrical into litres measures are used in pharmacy practice (Figure 4.8 Convert 6.5 microlitres Unit Abbreviation Litre equivalent into litres 1 litre 1 L (or 1 litre) 1 litre Using the table illustrated in Key Skill 4.3 Conversion between base volume units To convert between the base volume units. microlitres to litres). multiply by * conical measures 1000: * syringes.9 Convert 3643 millilitres In general. For example: 3643 / 1000 ¼ 3:643 litres * They are easier to fill without spilling liquid on the sides above the required level.3 Main volume units used in pharmacy Example 4.3). dient must comply with the current Weights and Measures Regulations and should be stamped accordingly. First convert 1 millilitre 1 mL 0. For more information on pipettes see Chapter 5 (page 71).000 001 litre Then convert from millilitres to litres: 0:0055 1000 ¼ 0:000 005 5 litres or ‘litres’ in full. divide by They have a number of advantages over cylindrical 1000: measures.g.001 litre from microlitres to millilitres: 5:5 / 1000 ¼ 0:0055 millilitres 1 microlitre 1 mL 0.g. 6:7 1000 ¼ 6700 millilitres In addition to these. multiply or divide the figure by 1000. volume con. tom of the meniscus should be in line with the desired * It is easier to rinse out the residue left after graduation mark (Figure 4. owing to the error. a syringe is used (see below) although a 5 mL syringe can be used to measure graduated volumes up to 5 mL. accurately.3 Selection of conical measures (250 mL. The markings on a beaker are only approxima- tions and cannot ever be used to measure any volume Figure 4. On the other hand. It is not good practice to use a conical measure to measure a volume that is smaller than half of the total volume of the measure. that the bot- * It is easier to drain out the preparation. Key formulation skills | 57 * They are easier to clean after use. ensure that your eye is in line with Bottom of meniscus to line up with Position of eye in volume mark relation to meniscus Volume marks Figure 4. it must be borne in mind that compared to cylindrical measures. with conical measures: * It is harder to read the meniscus accurately. For volumes less than 1 mL. ume of the liquid. Because of the shape of the measure.4). Stamped conical measures can be used to measure any marked amount but it is sensible to select the smallest measure for the desired volume. 10 mL and 5 mL). to measure 10 mL in a 10 mL conical measure than it would be to measure 10 mL in a 100 mL conical measure. * It is more difficult to estimate volumes between graduations (although in practice.4 Diagram to show which edge of the meniscus is to line up with the volume mark (note – the meniscus has been exaggerated in this diagram). Remember. 100 mL. when measuring liquids. it is more accurate. . 25 mL. for example. When reading the vol- draining viscous liquids into the preparation. this would be considered poor professional practice and is never done). it is important to avoid spilling any liquid ‘Checked by’ box on the product down the side of the measure as this could result in the worksheet. on a flat surface. this will involve moving 2 Check that the measure is clean and dry. Example 4. it is unlikely that the measure will be level. Once the check has been coloured card or paper behind the measure may help. may be difficult to see the bottom of the meniscus 5 Ask for a second check from another clearly.11 Measuring a colourless ple you are looking down onto the meniscus) errors in liquid: 25 mL potable water reading the correct volume will occur (Figure 4. In these cases. In addition to ensuring that your eye is in line with 1 Select an appropriately sized conical the meniscus. the meniscus. possible to read the volume accurately with the liquid 4 Measure 25 mL potable water in the moving about in the measure.5).58 | Pharmaceutical forms and their preparation Error of parallax Meniscus Figure 4. Do not lift the 3 Obtain a beaker of potable water to use as measure to the level of your head as it will not be stock. the member of staff initials the Finally. If your eye line is not level with the meniscus (for exam. sign your initials in the ‘Dispensed by’ box When measuring certain dark or coloured liquids it on the product worksheet. placing a piece of white or member of staff. your head down to the correct level. This will avoid any parallax errors. Ingredient Batch Quantity Dispensed Checked number by by Potable water N/A 25 mL . it is important that the measure remains measure. incorrect amount of liquid being added to the prepa. performed. It is also poor pharmaceutical practice. In many cases. Check the volume and stationary. Extract from product worksheet: ration.5 Diagram to show how an error of parallax can occur. Even if the liquid appears conical measure. you 3 Draw up liquid in excess of the required volume. it 9 Add the measured liquid to the preparation. Do is important once measured that the measure is NOT expel the liquid left in the nozzle.g. Medication strength Syringes There are a number of different ways that the strength Traditionally. small volumes have been measured in of active ingredients in a medicinal product can be pharmacy using a graduated pipette (see Chapter 5. above the vessel that the ingredient is to be transferred to for several seconds. Preparation calculations for this type of Volume marks Measuring edge of plunger product use the same basic principles. Key formulation skills | 59 When measuring a viscous liquid (e. This will involve holding the measure excess. However. . the following technique should be tical preparation can be expressed as the number of employed: millimoles per unit volume or mass of product. drained properly to ensure all of the measured liquid The syringe is calibrated to allow for this is transferred. upwards. To calculate the number of moles of active ingre- dient. 6 Tap the syringe to allow all the trapped air to come together at the top of the syringe.6). of moles of an ingredient or product 8 Re-invert the syringe over the liquid and push the Mass in grams plunger until the desired volume is reached.4). more recently.6 Diagram to show which edge of the plunger is to and so have to calculate the mass of active ingredient to line up with the volume mark when using a syringe. Key Skill 4. The 1 Select an appropriate syringe. syringes are less Millimoles accurate than pipettes. Martindale – The Extra Pharmacopoeia and the British Pharmaceutical Codex. The Number of moles ¼ Molecular mass desired volume is reached when the measuring edge of the plunger is in line with the desired volume mark in the syringe barrel (Figure 4. mole is the unit of amount of substance and there are 2 Move the plunger up and down a couple of times 1000 millimoles in a mole. will first need to know the molecular weight of the 4 Invert the syringe so the nozzle is pointing ingredient. The strength of active ingredient within a pharmaceu- For all syringes. It must be remembered that although their use is commonplace. Skill 4. Syrup BP). within the relevant ingredient monographs. Molecular masses for different ingredients are listed in the British Pharmacopoeia. volumes up to 5 mL.4 Calculating the number 7 Expel the air. expressed. be included in the preparation (see Example 4. per unit of preparation.12). The number of moles of ingredient is the mass of 5 Draw the plunger back a little further to allow all ingredient divided by the molecular mass (see Key the liquid in the nozzle to enter the main chamber. you need to know its molecular mass. 1 mL syringes have to perform calculations using the different methods been used to measure graduated volumes less than outlined in this section as all are in common use today 1 mL. To calculate the number of to check that it moves smoothly without sticking. It is important that all practitioners are able page 71). and 5 mL syringes to measure graduated in pharmacy. Sometimes a compounder will be asked to prepare a pharmaceutical preparation with a specified amount of active ingredient. millimoles of an ingredient in a medicinal product. the only difference being that you know the number of millimoles required Figure 4. expressed in millimoles. for example solution.05844 g (58. tissues do not behave as true semi- When solutions are formulated. Isotonicity * Therefore 1.9 g of sodium chloride per 100 mL of Sulphuric acid (H2SO4) contains two equivalents of solution is isotonic. If no net movement of solvent molecules occurs for two solutions separated by a perfect semi-permeable membrane. the solutions are the patient and so the product will need a either hypo. it is Because of the small quantities of electrolytes often worth indicating that if isotonicity is required. solutions intended for application to the eye.9% w/v solution (also known as normal saline).058 44 1. This is more commonly referred to H+ ions per mole because two moles of a univalent as a 0. OH–) are required to react with one mole of Although the adjustment of solutions to make sulphuric acid. the solutions are said to be iso-osmotic. swelling or contraction of the body tissue may Sodium Chloride BP. the equivalent weight of an element or compound is the weight that First.44 g. Milliequivalents and equivalent weights Within the body. HCl that the compounder will encounter is a sodium chlo- has one equivalent of H+ ions per mole as one mole of a ride solution that is isotonic with human blood. there will be 0. each millilitre will contain Equivalents per atomic or molecular weight 1.5 = 0. This is a common Chloride BP is required to prepare method for expressing the amount of electrolyte that 100 mL of Sodium Chloride BP is needed to be administered to a patient to correct an solution containing 1.60 | Pharmaceutical forms and their preparation Eq and so it follows that the number of Eq/mol is equal Example 4. ion (e. stating the number of equivalents (Eq). membrane in question. the number of H+ ions present in a solution molecules). tion containing 0.g. Reference texts element or compound. you will need to know the molecular combines chemically with one equivalent of another weight of sodium chloride.087 66 100 = 8.e.5 millimoles (mmol) Atomic or molecular weight ðg=molÞ ¼ per mL. One of the best ways to express this is by remain in equilibrium across a biological membrane. In the example given above. molecules) is given by: Therefore a 1 molar solution would contain 58. One of the most common pharmaceutical solutions cule of the substance.766 g of sues). Equivalent weight ðg=EqÞ * In a final solution of 1. the more common adjustment to the tonicity must take place after the term milliequivalents is used (there are 1000 mEq per addition of all the other ingredients to the solution . occur. 1 mmol contains 0.5 mmol. A solu- univalent ion (e. If the * We need to dispense 100 mL of solution to osmotic pressure is different (i. OH–) reacts with one mole of H+. valent counter ions required to react with each mole. The equivalent weight (for quote the molecular weight as 58. the osmotic pressure of the solution should be approx- * If the final solution contains 1.44 1000). permeable membranes (i. they are described as being isotonic with respect to the The term ‘equivalents’ refers to the number of uni. sometimes the com. If the two iso-osmotic solutions are able to of HCl).e. any used in pharmaceutical solutions. * If 1 mole of solution contains 58.5 mmol sodium electrolyte imbalance.or hypertonic with respect to body tis- total of 0.087 66 g.5 mmol contains It is important for some pharmaceutical solutions that 0.44.44 g of sodium chloride in 1 litre. them isotonic is beyond the scope of this book. some solute molecules are pounder is only interested in one half of an ion pair (for able to pass across the membrane as well as solvent example.5 mmol per imately the same as the osmotic pressure of the body mL.087 66 g per mL of tissue to which the solution is applied. chloride per mL Following on from the above.12 How much Sodium to the number of mEq/mmol).g. 4 Numerical value of different solubility pressure of the solution. 2 Preparation of a ‘space’ in the solvent ready for Solubility the transfer of the dislodged solute molecule. It would appear that of a solid in parts by volume (millilitres) of the final during the solution process the solute must be fitting solution. method for expressing the solubility of ingredients. . or in parts by volume (millilitres) of a liquid into ‘spaces’ within the solvent. insoluble’ (Table 4. following the percentage Soluble 1 in 10 to 1 in 30 symbol. broken down into three stages: nal product.4). 3500 mL water. For example. Slightly soluble 1 in 100 to 1 in 1000 The following terms are commonly used: Very slightly soluble 1 in 1000 to 1 in 10 000 * % w/w or percentage weight in weight (or % m/m – percentage mass in mass): This expresses the Practically insoluble 1 in greater than 10 000 amount in grams of solute in 100 g of product. % solid in liquid tion that range from ‘very soluble’ to ‘practically is interpreted as % w/v). for example ‘parts’ of solute in ‘parts’ of tion will be greater in volume than 11 mL but not product. expressed as % w/v and of liquids in liquids as % v/v. It is also common to see the solubilities of medica- When the type of percentage is not specified. by con. The solubility of product. descriptions Percentage strength Solubility description Numerical value Expressing the strength of a pharmaceutical product Very soluble 1 in less than 1 by ‘percentage’ can have a number of different mean- ings. It should be borne in mind that when a solute is Parts and solubility added to a solvent the liquid volume does not neces- Parts sarily increase summatively. In The process of dissolution in simple terms can be addition to expressing the concentration of a medici. 1 in 125 of glycerol. such as w/w or w/v. * value for a substance at 20 C is generally quoted % v/v or percentage volume in volume: This unless otherwise stated. as all are Sparingly soluble 1 in 30 to 1 in 100 in common use in modern pharmacy. expresses the number of millilitres of solute in Reference texts often quote solubilities in a range 100 mL of product. iodine is soluble 1 in 3500 of % v/w or percentage volume in weight: This water. ments described by a scale of terms derived by conven- vention the above rule will apply (i. These meanings are indicated by the addition of Freely soluble 1 in 1 to 1 in 10 suffixes. Solubilities are quoted in reference works in terms of 3 Positioning the solute molecule in the solvent the number of parts of solvent by volume required to space. if a solid Another common method for expressing the strength was soluble 1 in 11 this would mean that 1 g of solute of a pharmaceutical product is through the use of the would dissolve in 11 mL of solvent. Key formulation skills | 61 owing to their own individual effect on the osmotic Table 4. 1 in 8 of alcohol and 1 in 5 expresses the number of millilitres of solute in of ether. The resulting solu- term ‘parts’. whereas the same weight of iodine The strength of solutions of solids in liquids is usually would dissolve in only 5 mL of ether. It is important to be able to distinguish between the different types of percentage. * of solvents. For example. in parts by volume (millilitres) of the final solution. In this case 1 g iodine would dissolve in 100 g of product. This is interpreted as parts by weight (grams) necessarily as much as 12 mL. this terminology is also a common 1 Removal of a molecule from the solute.e. * % w/v or percentage weight in volume: This dissolve one part (by weight for solids or volume for expresses the amount in grams of solute in 100 mL liquids) of the medicament in question. In should the least soluble solid be dissolved first fol. In the late 1800s and early 1900s the dissolve 4 g of sodium bicarbonate. Although each of these methods has its merits. the quantity of vehicle used for dissolution must be reduced. 3 g * Solution is hastened by using as much of the dissolves in 3 2. others dissolve more rapidly but to with an increase of molecular weight. This decision was based on two factors: Example 4. First dissolve the least sol- Dissolution of more than one solute uble solid in slightly more than the minimum amount Questions arise when there are two or more soluble of liquid required for dissolution and then add in any solids to be incorporated into a single solution. solubility gives the quantity of solvent By the 1950s this advice had been changed. you need to two powders would be transferred to a mortar and know the solubility of the solute. A small amount of by reference to any official text. the choice of the most appropriate method is based on the solubility of the solids. or vice versa? cules of the least soluble compound will be different It should be remembered that the rapidity of solu.5 mL of water. or alternatively of vehicle required for the least soluble solid. In the British vehicle would be added to the mortar and mixed Pharmacopoeia it is quoted as 1 in 11. therefore the a smaller extent. Some substances are very soluble but clusion. each solid be dissolved individually in the solvent and Normally this will be achieved just using the amount then the two solutions combined. the saturated solu- means that 1 g of sodium bicarbonate is soluble tion thus formed would be decanted off and the in 11 mL of water. this would be regard- 4 g of sodium bicarbonate? less of the ease of solubility. The problem is also compounded by least soluble molecules will be larger than the more consideration of the use of each of the soluble solids.62 | Pharmaceutical forms and their preparation addition of the antioxidant as the first solid introduced Example 4. if one compound is an antioxidant and ‘spaces’ than those needed by the more soluble the other a compound susceptible to oxidation. required: The idea was now to add the soluble powders to the vehicle at the same time. The assumption made was that three-quarters of the vehicle would be a suitable volume for dissolution.1). Therefore.13 What volume of to the vehicle would seem the commonsense answer to potable water is required to dissolve prevent oxidation of the second.14 What volume of * The volume occupied by other ingredients in the potable water is required to dissolve 3 g of a solid which is soluble in 2. the ‘spaces’ occupied by the mole- lowed by the most soluble solid. more soluble compounds. from the ‘spaces’ occupied by the molecules of the tion does not depend entirely on the degree of solubil.5 = 7. . The quantity of vehicle used 4 11 ¼ 44 mL of water did not reflect the solubility of any of the soluble pow- ders to be incorporated. as the degree of solubility generally decreases are slowly soluble. but if it should. 1 g dissolves in 2.5 preparation would rarely exceed the remaining parts of water? one quarter. simplistic terms. Historically this problem has been dealt with in To calculate the required amount of solvent to differing ways. process repeated until all of the soluble solids had Multiplying the amount of sodium bicar- been incorporated into small amounts of saturated bonate required in the preparation by the solution. solvent as is convenient. Should other soluble solids in increasing order of solubility. This would be a logical con- ity of the solid. This with the powders using a pestle. The solubility thoroughly mixed together (using the ‘doubling-up’ of sodium bicarbonate in water can be found technique – see Key Skill 7. soluble molecules and will therefore occupy bigger For example.5 mL of water. the compounds. of solvent Dilutions It is not uncommon for a compounder to have to dilute a concentrated stock product to make either an ingre. aqueous solutions of potassium a specified strength.5 mL of a 20% errors of final concentration. 1 g in 5 mL and However. buffering agents should be included to adjust the final pH to neutral in order to avoid irritation. So there are 2 g in 10 mL.1% w/v solution. for oral use should be diluted with water before administration. There are two main ways to express dilutions you need to calculate the quantity of the con- (where ‘x’ is the volume in millilitres): centrated solution that contains the same * 1 in x (e. appropriate them. Next. Potassium Citrate Mixture BP con- tains 3 g potassium citrate and 500 mg citric acid in Key Skill 4.g. you need to calculate the total amount of for example dressing soaks. usually by solution the addition of an appropriate amount of sodium * 1 : x (or 1 to x) – 1 part of solute to x parts chloride.g. 20% w=v solution ¼ 20 g in 100 mL It is important to understand the difference between these because they appear initially to be the same.5 mL. Example 4. * 1:x (or 1 to x) (e. Additionally. a dilution w/v solution would be required to make expressed as 1 in 10 means that there is one part of 500 mL of a 0. The final pH of a solution must be con.1% w/v solution using a 20% w/v or a product itself. there is 0.5 and 9. 1:10 or 1 to 10). 10 mL). that markedly hypertonic solutions concentrate. though. Problems arise when it is neces- citrate have a pH between 7. a dilution expressed as 1:10 means caments can only be achieved within a particular that there is one part of solvent to 10 parts of solvent pH range. It should be sary to produce differing strengths of solution from a noted.15 Prepare 500 mL of a dient for incorporation into a pharmaceutical product 0. any misinterpretation can lead to large 0. how much of a concentrate is to be diluted with a tions intended for oral use. solvent in 10 parts of final solution (e. 1 mL of con- centrate and 9 mL vehicle with a final volume of . Therefore.g. which must be mixed with approx- imately 200 mL potable water immediately before There are two main methods for expressing administration. For example. 1 in 10) amount of active ingredient. some products are concentrated stock solution dispensed to patients for further dilution at home. some cases. 1 mL of concentrate and 10 mL vehi- sidered in conjunction with the intended use of the cle with a final volume of 11 mL).5 Dilutions each 10 mL dose. for example communicating to patients There is some latitude when compounding solu. dilutions.5 g in 500 mL. For example. First. However.g. this is a rigid approach can accommodate solutions with a wide range of pH to dilution that will always result in a final solution of values. Therefore 2. as the gastrointestinal tract specified amount of diluent. (or 1 in 11) (e. It is important that the two are not Where solutions are compounded for external use mixed up as there is a key difference between on mucous membranes or broken skin. Although useful in product. In both cases it is neces- active ingredient required in the final solution: sary to specify the required amount of concentrated product that needs to be mixed with a specified 0:1% w=v solution ¼ 0:1 g in 100 mL amount of diluent. * 1 in x – 1 part of solute in x parts of final such solutions should be rendered isotonic.5 g in 2. Similarly. Key formulation skills | 63 In some cases the dissolution of certain medi. If a variability of strength is required. It is therefore essential that all practitioners are able to calculate both the quantity of a concentrated solution and the quantity of diluent that needs to be mixed to produce a specified quantity of the correct strength of a final product. making it more suitable for use in a hospital setting. there are 9 g in 1000 mL and you would need 45 g in 5000 mL.5 mL. therefore 1 g in 2. Therefore. .5 mL of a 40% solution Example 4.64 | Pharmaceutical forms and their preparation Example 4. each diluted preparation will have to be either individually pre- pared or a concentrate given and supplied with com- prehensive and often complex dilution instructions.16 How much solute is Example 4. 2. solution? 5% ¼ 5 g in 100 mL Therefore you would need 1 g in 20 mL.17 How much solute is would be required to produce 1 litre of a 1 in required to produce 20 mL of a 5% 1000.9% 40% w/v solution would be required w/v solution? to produce 1 litre of a 1 in 1000 solution? 0:9% ¼ 0:9 g in 100 mL 1 in 1000 ¼ 1 g in 1000 mL Therefore. What volume of a 40% w/v solution contains 1 g? 40% w=v ¼ 40 g in 100 mL There are 4 g in 10 mL.18 What quantity of a required to produce 5 litres of a 0. although fairly simple. the compounder adheres to strict intended recipient of the medication and the com- procedures to ensure the safety of the patient for pounder. requirements The measures indicated below.5 Extemporaneous dispensing Guide to general good practice requirements 65 Solvents and vehicles 76 Standards for extemporaneous dispensing 66 Ointment bases 78 Premises' standards 66 Suppository and pessary bases 80 Equipment requirements 67 Preservatives 80 Avoidance of contamination 67 Antioxidants 82 Suitable record keeping 67 Buffers 84 Equipment 67 Thickening and suspending agents 85 Mortars and pestles 67 Wetting agents 86 Tiles 69 Emulsifying agents and emulsifying waxes 87 Stirring rods 69 Colourings and flavourings 87 Pipettes 69 Storage and labelling requirements 91 Suppository moulds 69 Storage 91 Tablet and capsule counting equipment 72 General principles of labelling 91 Water baths 74 Pharmaceutical packaging 96 Product formulae 74 Tablet bottles 96 Official formulae 75 Medicine bottles 96 Unofficial formulae 75 Cartons 98 Ingredients 75 Ointment jars 99 The British Pharmacopoeia 75 Guide to general good practice whom the extemporaneous formulation is intended. Because of the diversity of the types and . undertaken in a logical and safe manner for both the pounding process. are designed to ensure that the compounding process is It is of paramount importance that. during the com. those found in food kitchens. patients who visit a pharmacy Appropriate work area with a prescription for a product needing to be extem. * The floor should be covered but in such a manner uct with either dirt or microorganisms from the as to be easily cleaned. Hygiene standards in a pharmaceutical environment should bench. So although this is small-scale production. industrial methylated spirits dispensing (IMS)). if not higher than. the pre- any open cuts are covered. This is because medications are being pre. This gloves) may also be required. see page 92. Before starting to compound a product. and prepared in such a way as to ensure the and if the ventilation within the work area is inade- products meet the required standard for quality assur. accurately Some pharmaceutical ingredients are highly volatile prepared. found in a manufacturing unit. when weighing or measuring more of the ingredients to be incorporated into the prepara- than one ingredient. facemasks. see section on same careful attention to detail is required as would be Premises’ standards below. Weighing and measuring procedure During weighing and measuring.g. of the individual compounder to assess the risk posed by any pharmaceutical ingredient and to ensure that the correct safety equipment is in use. pared before starting the compounding procedure. For further be as high as. pared for patients who may already be ill. conversely. weighed or measured ingredient into a product as soon During the compounding process. ment.g. In addition to the cleanliness of the work area. Similarly. a licensed manufacturing unit. eliminating the pos- sibility that an unlabelled product will be left on the Personal hygiene is extremely important. Clean work area and equipment The cleanliness of the work area and equipment used * Premises’ decoration should be of a good basic during the compounding procedure is of paramount standard. importance. will enable the product to be labelled as soon as it has Personal hygiene been manufactured and packaged. it can be very easy to mix up differ- A clean white coat should be worn to protect the com- ent pharmaceutical ingredients as many ingredients pounder from the product and. ensuring In addition to the points highlighted above. For additional premises standards. Label preparation The following measures must be taken into The label for any pharmaceutical product must be pre- consideration when preparing a product extempo. the staff. depending on the nature is not possible. the work area and equipment should be cleaned with a Standards for extemporaneous suitable solution (e. or from ingredients from a previous poraneously. It also reduces the possibility of the product being mislabelled and given to the wrong patient. If this should always be worn and. in the pharmacy must be suitable for use. additional safety equipment (e. It is the responsibility will avoid any accidental cross-over of ingredients. . safety glasses as possible to prevent any accidental switching. can be considerable if attention is not are significant factors in the production of safe and paid to the cleanliness of the work area and equip- effective extemporaneous formulations. quate this could cause problems for the compounding ance. unless strict guide- Personal protective equipment lines are followed. The risk of contaminating the final prod. paper as soon as it has been weighed or measured. the prod- resemble each other. The products produced Both lighting and ventilation need to be adequate. surroundings. surfaces should be smooth. which must be allowed to dry fully. place each on a piece of labelled tion. long Premises' standards hair should be tied back and hands washed. It is preferable to incorporate a uct from contamination from the compounder.66 | Pharmaceutical forms and their preparation number of preparations that can be formulated extem. eration needs to be given to the work area itself to dards within a pharmacy to be comparable to those of ensure that it is suitable for its intended purpose. mises where an extemporaneous product is being pre- pared need to be of an appropriate standard. As indicated above. details on the preparation of a suitable label. This raneously. compounder experience and expertise preparation. consid- poraneously prepared are entitled to expect the stan. page 57) * Refrigerators used in pharmacies must be capable of range of graduated syringes and/or pipettes (see storing medicines between 2 C and 8 C and must be pages 58 and 71) * equipped with a maximum/minimum thermometer. Poor record keeping can lead * to dispensing errors which could result in the patient heating ring (means of boiling water) * receiving a product other than that intended by the hot water bath (see page 74) * prescriber. range of glass beakers * In addition to recording the compounding process range of accurate graduated conical measures for extemporaneously dispensed items. Extemporaneous dispensing | 67 impervious to dirt and moisture. * make emulsions. As a Suitable record keeping is a vital part of good extem- guide. the following items should be available: poraneous preparation. electronic labelling system. compounders should adhere to the ous dispensing. fridge temperatures) should be routinely recorded. although ideally five years range of suitable information sources * would be advisable. range of suitable containers for prepared products Extemporaneous record sheets should be kept for a (see page 97) * minimum of two years. . and should be * Do not allow raw materials or the final product to clean and uncluttered.1. Equipment requirements Suitable record keeping A dispensary should have sufficient equipment avail- able in order to be able to operate effectively. clean refrigerator. * mix powders * Do not leave weighed and measured items * mix powders and liquids unlabelled on the work surface.1. cold water. * reduce the particle size of powders * Do not return material to stock containers once * grind crystals into powder form removed. Therefore the completion of the record will Class II dispensing balance or electronic be another safety check for the patient and is an essen- equivalent (see Chapter 4. A suggested layout for a pestles (see page 68) * dispensing record sheet is given in Figure 5. large and small glass or ceramic tiles (see page 71) * This should be checked each day the premises are open range of spatulas and glass stirring rods (see page and the maximum/minimum temperatures recorded 71) * to ensure that the equipment is operating correctly thermometers * and that patient safety is not compromised. suppository moulds (see page 72) * The notes section is added to allow for any special tablet and capsule counting equipment (see page 73) * instructions with regard to method of preparation. Avoidance of contamination Equipment To avoid contamination of any extemporaneously A wide variety of equipment is used in extemporane- prepared product. * The procedure to be followed on receipt of a pre- There should be a functioning. other records (stamped by the weights and measures inspector) (e. * scription for extemporaneous preparation is described There should be a supply of mains (potable) water. page 51) * tial part of any standard operating procedure for range of glass and earthenware mortars and extemporaneous dispensing. depending on the product type to be following guidelines: prepared.g. (see Chapter 4. Mortars and pestles * Keep the dispensing area clear of unnecessary items. in Box 5. Mortars and pestles are used to: * Do not leave lids off stock bottles: always replace immediately after use. come in contact with the hands (if necessary wear * Sinks should be clean and have a supply of hot and gloves). * Ensure all equipment is clean and dry prior to use. It should be noted that the mortar is the bowl and suitable for size reduction of powders. 8 Select the container to be used for the completed product. Powder that is spilt into the drawer sticks to the weights and renders them inaccurate. for mixing powders with other . b When weighing on a traditional Class II dispensing beam balance. c Signed by the prescriber. d Suitably dated by the prescriber. This will prevent any liquid running down the outside of the bottle and staining the label. 4 Copy out the formula onto the extemporaneous work record sheet (which must be kept in the pharmacy for a minimum of two years) (see Figure 5.1 Dispensing procedure on receipt of a prescription for extemporaneous preparation Upon receipt of a prescription. they are efficient when grinding crystals into ment. the basic procedure to be followed is always the same: 1 Check the prescription is legally valid and contains the following information: a Name and address of the patient. 7 Select the equipment to be used for the preparation of the product. remember: i Place a white piece of paper under the scale pan before weighing. Glass mortars are particularly (Figure 5. 9 Select the first item to be measured or weighed and make a note of the batch number used.2).1). check it again when measuring/weighing the ingredient. They are ideal for the size reduction and its pestle are very smooth. 5 Recheck any calculations made. b Age or date of birth of the patient if under 12 years. making them less of powders. iii Use a spatula when weighing (remember to clean the spatula between each different powder that is weighed). 6 Test the dispensing balance before use (particularly important if the scales have not been used for some time). useful when dissolving small amounts of In pharmacy two main types of mortar and pestle medicament or when incorporating substances are used: such as potassium permanganate or dyes that are absorbed by and stain porcelain mortars. 2 Check your interpretation of the prescriber’s instructions. a Is the formula official or unofficial? b Are all ingredients within a safe dosage limit? c Are all ingredients compatible? 3 Prepare a label for the product. although the pestle is the pounding/shearing/grinding imple.68 | Pharmaceutical forms and their preparation Box 5. * Glass – These are not usually used for the * Porcelain – Generally much larger than their glass production of large quantity products as they are counterparts. these lend themselves to larger scale usually fairly small. iv Ensure the scale pan is cleaned between each weighing procedure. so compounders mix in a mortar with a pestle powder form. 10 When the preparation is ready to be dispensed. and a third check should be made when returning it to the stock shelf. Note when selecting an ingredient from stock. The surfaces of a glass mortar production. ii Keep the drawer of the balance closed. check the label. transfer it to the final container and label. a When measuring a liquid keep the label into the palm of the hand. v Remove the weights from the scale pan immediately after use. 2 g. Repeat the process until the powder size is suitably reduced. page 172). piece of equipment used to prepare ointments by See Suppositories video for a demonstration of means of trituration (see Chapter 9. suppository moulds come in a range of pestle therefore follows a spiral track around the mortar. It should be noted that each part of the mould is designed to match and will be marked Ointment tile or slab is the term used to describe the accordingly to show this. as with mea- way to use the pestle is to start in the centre of the sures. Stirring rods are used to agitate liquids to speed up the After removal from the mould. the suppositories process of dissolution of solids. The Traditionally. inspector (Figure 5. stances to fine particles. Suppositories and pes- as much bearing on the interior surface of the mortar saries are made using the same moulds (see Figure 5. gitudinally. When measuring small volumes a syringe is used. the individual suppositories formed bottomed mortar will need a round-headed pestle to weighed. and for Pipettes the preparation of emulsions. This a guide. . For mortars are flat bottomed and need a flat-headed accurate calibration a mould would need to be filled pestle to produce efficient mixing. and removal of the suppositories should be Tiles relatively easy. board. they can be lubricated easily before use. Care must be taken not to stir too vigorously as this Nowadays. a round. The most effective sure volumes from 5 mL to 0. minium foil is recommended for wrapping.5). As the moulds open lon- will take a comparatively long time to achieve. tain an insoluble medicament. The use of a round-headed pestle in a used for pessaries. which is designed to deliver a set amount of the liquid. These weights are nominal Mortars and pestles need to be matched. are made of metal with two or three sections held ing as the required result will either not be achieved or together with a screw fixing. 4 g and 8 g. Extemporaneous dispensing | 69 powders. the powder is placed in the Syringes have a high degree of accuracy and are readily mortar and the pestle is used to rub down in a lateral available in most pharmacies (see Chapter 4. with base alone. Ideally the pestle should have ity (see Chapter 11. When using a mortar and pestle to reduce sub. in small-scale production the use of alu- may cause the stirring rod to break. a 300 mm square is a suitable size for around is an advantage when making suppositories that con- 500 g of ointment (Figure 5. page 148). Similarly. As quickly because of their efficient heat transfer. if necessary.3). shearing manner on the powder. as size will permit.2. Their use is described in Box 5. Some and imply calibration with Theobroma Oil BP. reverse the process. sizes: 1 g. These are normally used to be dispensed in partitioned boxes of paper- between 20 and 30 mm in length and made of glass.1 mL and. as the speed at which mixing or when no weight is specified a 1g mould is used for grinding will occur depends on the amount of contact suppositories and the larger 4 g and 8 g moulds are of the surfaces. and the mean weight taken as the true capac- produce efficient mixing. page 148) or lev- the assembly of a suppository mould. either ‘drainage’ revolution until the sides of the mortar are touched. for mixing powders with liquids. The pestle is given a However. syringes are less accurate than pipettes and circular motion accompanied by downward pressure so traditionally small volumes have been measured (not too much pressure as the powder can become com. making the circles smaller with each Suppository moulds revolution until the centre is reached again. gradually increasing the diameter of the circle with each Two types of pipette are employed. Tiles are usually made of glazed porcelain or glass and should be large Metal moulds allow the suppositories to set enough for the quantity of ointment to be prepared. using pipettes. metal or plastic and lined with waxed paper.4). Graduated pipettes were used to mea- pacted on the bottom of the mortar). flat-bottomed mortar or a flat-headed pestle in a The traditional moulds for small-scale production round-bottomed mortar is very inefficient and frustrat. because it does not allow time for the suspended solids to settle by Stirring rods sedimentation. igation (see Chapter 9. then or ‘blow out’. page 58). they must be stamped by a weights and measures mortar and make a circular motion on the powder. 70 | Pharmaceutical forms and their preparation Extemporaneous Dispensing Record Number: Date: Pharmacist Compounder: in charge: Patient name: Prescriber’s name: Patient address: Prescriber’s address: Item ordered and dosage: Master formula and source: Dose check and reference: Figure 5.1 An example of a dispensing record sheet. . 1 (Continued) . Extemporaneous dispensing | 71 Compounder’s signature: Pharmacist’s signature: Calculation: Compounder’s signature: Pharmacist’s signature: Product formula Item: Quantity: Ingredient: Batch number: Quantity: Dispensed by: Checked by: Notes: Label: Figure 5. disposable plastic moulds are avail.2 Porcelain and glass mortars and pestles. Manual counting Figure 5. These are relatively cheap and can even be used demy paper which is overlapping another sheet of to dispense the finished suppositories without removal white demy.3 Ointment tile and spatulas. a perforated counting tray. out some tablets or capsules onto a piece of white able.4 Selection of pipettes with pipette filler. required is counted in tens using a spatula and trans- See Suppositories video for a picture of a dis. ferred to the second piece of paper. This method involves pouring Alternatively. the paper is Figure 5. Tablet and capsule counting equipment Tablets and capsules can either be counted manually or using some kind of device. the medicines are not touched by hand. number to be dispensed is achieved. such as a tablet triangle or a capsule counter. or by electronic counting with an electronic balance or pho- toelectric counter. but the main factor is that during the counting process. The number of tablets or capsules and the requirement to rewrap. All of these methods have their advantages and disadvantages. Once the required posable suppository mould. The last edition of the (British) Pharmaceutical Codex (12th edition) outlines the manual methods of count- ing tablets or capsules.72 | Pharmaceutical forms and their preparation Figure 5. . Electronic counters Electronic balances transferred into a trough or funnel and the tablets or A weight reference sample of between 5 and 20 tablets/ capsules transferred to a suitable container. 1 Select a pipette that is suitable for the Counting triangle/capsule counter required volume to be measured and The counting triangle is a fast and accurate way of graduated suitably. Problems capsules is weighed and from this a microprocessor with this method are that demy paper is becoming computes the total number as further tablets/capsules increasingly difficult to obtain and therefore also quite are added to the balance pan or scoop. into a small clean. the one that has a counting tablets based on Pascal’s triangle.2 How to use a pipette be maintained to ensure accuracy. quite quickly using this type of counter but the novice 8 Remove any excess droplets of fluid on the can find it quite frustrating. and the degree of concentration that must Box 5.5 Selection of metal and plastic disposable suppository moulds. In each case the 2 Check whether the pipette is a ‘drainage’ tablets or capsules are placed on the counter and any type or ‘blow out’ variety. requiring the trays to be changed for different sizes and 7 Adjust the meniscus as required to types of product. maximum volume nearest to the volume the capsule counter was designed to allow easy to be measured. Likewise. Perforated counting tray 6 Insert the tip of the pipette into the liquid This is a box of clear Perspex which has trays of per- and suck up a sufficient amount of the forations of varying sizes. The main Figure 5. . cated and time consuming. excess removed using a spatula. The larger metal mould would be used to manufacture pessaries. counting of capsules in rows of 10.6). dry beaker (never pipette from a stock bottle). i. The other disadvantage of outside of the pipette by wiping with a this type of counter is that cleaning is more compli- non-shed disposable towel. Extemporaneous dispensing | 73 expensive. An experienced operator can count measure the appropriate volume. of equipment speed up the counting process and are 4 Attach a bulb or teat over the mouth of the easy to clean. Sugar-coated tablets and soft gelatin pipette (never use mouth suction). These simple pieces 3 Check that the pipette is clean and dry. The tray can be used to liquid so that it is well over the required count tablets or capsules but has the disadvantage of volume. capsules are more difficult to count using these meth- 5 Pour some of the solution to be measured ods (Figure 5. 9 Transfer the volume required to the final admix of the product.e. 1994. important when using a water bath to ensure that The Council for the Royal Pharmaceutical Society enough water is placed in the bath and that it is of Great Britain issued the following advice regarding replaced when necessary. special care should be taken needs to be recalibrated for each type and size of dos. This is from a bulk container holding damaged con- more problematic when dealing with very small tablets tents. Between counting the balance particularly serious. and also its bath to be boiling rapidly. disadvantage is the reliance on the individual dosage uncoated tablet. pages 413–414) counting. there is no necessity for the water in the whole tablets and fragments of tablets. This causes very little problem in drugs. Product formulae used in pharmaceutical practice can counting devices should be carefully cleaned be divided into two distinctly different categories: offi- after each dispensing operation involving any cial formulae and unofficial formulae. and as the dosage form passes Normally the item to be melted is placed in an evapo- down it interrupts the passage of a light to a photo- rating basin over a water bath containing hot water electric cell. inaccuracy when counting transparent capsules such The heat source for the water bath was tradi- halibut liver oil capsules. Some problems are encountered if the bal- ance is not well sited as it is very sensitive to vibration and air movement. ((British) Pharmaceutical Codex. to prevent the bath boiling the use of tablet counters: dry. A major drawback with these tionally a Bunsen burner. the top of the machine. Severe allergic reactions can be initiated in pre- viously sensitised persons by very small amounts of certain drugs and of excipients and other Product formulae materials used in the manufacture of tablets and capsules. As cross-contamination with penicillins is or sugar-coated tablets. when dispensing products containing those age form counted. . As most products only need to be tablet counter is its inability to discriminate between melted gently.74 | Pharmaceutical forms and their preparation Figure 5. In order to minimise that risk. 12th practice and does not really detract from the speed of edition. It is also required if an ointment The item to be counted is poured through a hopper at or cream is to be prepared from first principles. The main limitation with this type of and allowed to melt. Water baths A heat supply is needed for the production of suppos- Photoelectric counters itories and pessaries. or any coated tablet or capsule forms being of a consistent individual weight.7). It is order to clean it effectively. but latterly this has been systems is the necessity to dismantle the system in replaced by an electric hotplate (Figure 5.6 Counting triangle and capsule counter. that can be found in the British Pharmacopoeia (BP). providing details of the quality 92). A magistral formula is any precedence. graphs from the European Pharmacopoeia. It should be stressed that when compounders are the British Pharmaceutical Codex (BPC). It is the authoritative collection of standards for uct that is compounded extemporaneously (see page medicines in the UK. the ‘BP’ in the name ‘Kaolin Mixture BP’). 92).g. ‘official’ if the full formula can be found in one of these official texts.7 Water bath and heater. in the European Pharmacopoeia and the British the product will be deemed unofficial. . This is usually indicated by the presence Ingredients of the designation after the product name (e. it is medicine and pharmacy. The entire If the formula of the product that is to be made extem. In these cases. preparations and articles used in current edition of the official text in question. action and use statement respective quantities on the product label (see page and a list of British Pharmacopoeia preparations). it is In addition. Even if the quantity of one of the ingredients Should there be any discrepancy between the entries differs only slightly from that of an official formula. steps must be European Pharmacopoeia (EP) or the British taken to ensure that the formulation is stable and that Veterinary Codex (BVetC). A product is deemed there are no compatibility issues (see Chapter 13). termed an ‘unofficial formula’.8). if the formula is not taken from the of substances. this is two horizontal lines bearing the symbol ‘Ph Eur’. Pharmacopoeia (or any other official text).g. the presented with unofficial formulae. the The term ‘magistral formula’ is also used in extem. respective quantities on the label for any official prod. However. It incorporates the British usual to include the year of the reference in the product Pharmacopoeia (Veterinary) and contains mono- title (e. The British Pharmacopoeia As the formula for any official product can be The British Pharmacopoeia is published on the recom- found by examining the relevant official text. European Pharmacopoeia text is then bounded by poraneously cannot be found in any official text. Official formulae medicinal product prepared in a pharmacy in accor- Traditionally in the UK. Paediatric Chalk Mixture BP 1988). entry in the European Pharmacopoeia would take poraneous dispensing. official formulae are those dance with a prescription for an individual patient. All European entries in the British Pharmaco- poeia are identified by the use of the European chaplet Unofficial formulae of stars alongside the name (Figure 5. Extemporaneous dispensing | 75 Figure 5.g. it is mendation of the Medicines Commission in accor- not necessary to include a list of ingredients and their dance with Section 99(6) of the Medicines Act 1968. statements that are relevant to UK necessary to include a list of the ingredients and their usage have been added (e. unsuitable for a particular preparation.8 The European chaplet of stars. the European Pharmacopoeia Commission following Some drugs are insoluble or only poorly soluble in their preparation according to a procedure of harmo. terms used to describe water. the British Phar- macopoeia states: The term Water used without qualification in formulae for formulated preparations means either potable water freshly drawn direct from the public supply and suitable for drinking or Figure 5. The inclusion of a triangle within the chaplet of Care must be taken to select an appropriate water type stars denotes monographs that have been adopted by when preparing aqueous vehicles when compounding. . Care should be taken to identify that the source of water used originates in a suitable mains supply rather than a storage system. as the latter may contain a potentially dangerous range and num- ber of pathogens. It should be product or ingredient demonstrable at any time palatable and suitable for drinking. Solvents and vehicles A number of liquids can act as pharmaceutical sol- vents. The monographs that have been adopted by the European latter should be used if the public supply is from Pharmacopoeia Commission from Japan or the United States of a local storage tank or if the potable water is America. In such cases it is necessary to employ an nisation agreed between the bodies responsible for the organic compound.76 | Pharmaceutical forms and their preparation * gives minimum standards for efficacy and acceptability for inclusion in a medicinal product. The most common solvent used in pharmacy is water. Potable water The British Pharmacopoeia: Water that is taken directly from the mains drinking * provides standards concerning the quality of a water supply is termed ‘potable water’. United States of America (Figure 5. there are a number of Figure 5. It should be noted that in some geographical areas water from the mains supply may be inappropriate for use in compounding certain pro- ducts owing to excessive hardness. In most cases. extremes of pH or the presence of solid contaminants.9). water. Water In the pharmaceutical context.9 European chaplet of stars with a triangle denoting freshly boiled and cooled Purified Water. On the use of potable water. each reflecting the source. takes into account that products or ingredients Potable water is not suitable for preparations used may deteriorate over time for systemic injection. quality and purity of the water described. Anything that is subject to a monograph must comply with the complete monograph for the whole of its period of use. during its accepted shelf-life potable water is suitable for compounding prepara- * does not give minimum production standards but tions intended for either internal or external use. either alone or as a co-solvent with European Pharmacopoeia and those of Japan and the water as the vehicle. see Chapter 2). Fractionated coconut oil has of some of the galenicals used in pharmacy (e. asthmatics. for Purified water is water for the preparation of whom the use of alcohol in such preparations must be medicines. Water for preparations When used in products for external use. Its viscosity also when water is used as vehicle (water for injec. and hence tion of medicines for parenteral administration local action of the drug is prolonged. external use Industrial Methylated Spirits (IMS) is ionisation or distillation. The main recipi- ents of liquid medicines tend to be young children. Extemporaneous dispensing | 77 Purified Water BP lice). tinc. tures. The British Pharmacopoeia definition of Purified There are problems with the use of ethanol in Water BP is as follows: medicines intended for internal use. preparations although its use is not as wide-ranging The British Pharmacopoeia definition for Water as that of water or alcohol. cosity prevents rapid dilution with saliva. It is often used in prepara- for Injections BP is as follows: tions to treat the throat or the mouth because its vis- Water for injections is water for the prepara. of aqueous formulations were designed for use by commercially produced Water for Injections BP con. unless otherwise Muslims). In extemporaneous dispensing it Arachis oil is also known as peanut oil. the increase in cases of allergy to nuts and the subse- larly useful if rapid evaporation is required (e. which may be used in situa- Glycerol is another solvent used in pharmaceutical tions where other water sources are questionable. rendering it unfit for inter- ing for even short periods and therefore should be nal use because of the toxicity of the methanol (methyl freshly boiled and cooled when used for compounding alcohol). Therefore the use of alcohol is generally limited. . albeit expensive. it is used in the manufacture fat-soluble ingredients. unacceptable. tions in bulk) and for dissolving or diluting Propylene glycol substances or preparations for parenteral This is widely used as a substitute for glycerol. source of water Glycerol of known high quality. a medicine containing alcohol may also be justified and authorised. Oils such as arachis oil have been used as solvents for arations for internal use.g. Although ethanol Oils (ethyl alcohol) is rarely used as a lone solvent for prep.g. and latterly is normally used for the production of lotions for the use of this oil as a vehicle has declined because of external application to unbroken skin. It is administration (sterilised water for injections). be sterile and apyrogenic. It produces less viscous solutions Alcohol than glycerol. makes it suitable for use as a solvent for ear drops. addition of wood naphtha. For patients of certain faiths (e. duty and is therefore cheaper than Ethanol BP. Purified water supports the used.g. for quent increase in risk of anaphylaxis in susceptible insecticidal lotions applied to hair for the treatment of individuals. pyrogen free and sterilised. in susceptible individuals when using alcohol-based Water for Injections BP lotions. It is particu. problems Either freshly drawn potable water or freshly boiled have been encountered because of the volatile nature and cooled purified water would qualify as water for of the solvent. After water. The problem was considered so serious that a number pounding aqueous preparations for parenteral use. also been used as a vehicle for fat-soluble ingredients. stitutes a convenient. other than those that are required to questioned. this is probably the next most important solvent used pharmaceutically. IMS is ethanol that has been ‘denatured’ by the rapid growth of microbiological organisms on stand. used as a vehicle for ear drops and as a co-solvent in aqueous vehicles. Although this water type is used chiefly when com. As IMS is ‘denatured’ it is free from excise pharmaceuticals. insecticidal preparations for the treatment of head lice. This was highlighted by the use of alcoholic This water is distilled. In most cases in the formulation of products for Purified water is prepared from potable water by de. Asthma attacks have been precipitated preparations. ditions and also for overnight use. and this in turn improves * as a vehicle from which drugs may be absorbed by hydration of the skin in dry scaly conditions. is less likely to cause (i. Yellow Soft Paraffin BP.78 | Pharmaceutical forms and their preparation Ointment bases bases are very stable as they are a mixture of hydro- Ointment bases are usually fatty. It has a solidifying point of 50–57 C. They are both semi-solid mixtures of * miscible with skin secretions hydrocarbons obtained from petroleum. Its main use in ointment bases is to Hydrocarbon bases reduce their viscosity. Coal Tar BP or * irritate the skin Ichthammol BP). Paraffin bases are usually used when the medicament * Paraffin Ointment BP – This is an ‘official’ is not intended to be absorbed systemically. There are two distinct purposes for atmospheric conditions of storage. It is accepted nowadays that although * interfere with the normal functioning of the skin White Soft Paraffin BP may produce products that by preventing radiation of heat from the skin or are more ‘pleasing to the eye’. waxy or synthetic in carbons. white or pale * retard wound healing ingredients. They are intended to soften but not melt when tendency to react with either the medicament or the applied to the skin. agent in ointment bases. Traditionally Yellow Soft Paraffin The base should not: BP has been used when an ointment includes dark- * cause sensitisation to the skin coloured ingredients (e. properties: Common hydrocarbon bases include: * stable * Yellow/White Soft Paraffin BP – Both Yellow and * easily removable from the skin White Soft Paraffin BP are widely used ointment * equally efficient on wet or dry skin bases. chiefly saturated. because the melting point may vary slightly from batch to batch). not ‘clog up’ the pores) sensitivity reactions in susceptible patients. White * miscible with water-soluble and fat-soluble Soft Paraffin BP has been highly refined and is medicaments decolourised (bleached Yellow Soft Paraffin BP). These White Soft Paraffin BP 900 g .e. which have virtually no nature. Hard Paraffin BP 30 g bined to produce a base of suitable consistency. mixture of the liquid hydrocarbons obtained from petroleum. * inactivate or interfere in any way with any * Hard Paraffin BP – This is used as a stiffening incorporated medicament. the skin Ointments are preferred for the treatment of such con- * as a protective or emollient for the skin. Mixtures of 50% The base employed will depend on the intended White Soft Paraffin BP and 50% Liquid Paraffin BP use of the ointment but all should have the following are regularly used for the treatment of very dry skin. * capable of allowing transference of medicaments Both have similar properties with a melting point rapidly to the skin range of 38–56 C (the melting point range is * approximately neutral with regard to pH. It is a mixture of solid hydrocarbons obtained from petroleum or shale Ointment bases can be divided into five main oil. Various hydrocarbon ointment base consisting of: mixtures of hard. an ointment base: The paraffins inhibit water loss from the skin by forming a greasy layer. the unbleached preventing the excretion of various secretions form. this is a emulsifying bases * water-soluble bases. soft or liquid paraffins may be com. Because groups: of its relatively high melting point it is also added * hydrocarbon bases to other paraffins to increase the melting point of a * fats and fixed oil bases product and therefore increase its suitability for * absorption bases use in warm climates. * * Liquid Paraffin BP – As the name suggests.g. White Soft Paraffin BP was * dehydrate the skin reserved for products with colourless. bases for application to the scalp. . emulgent carbon base to increase its emollient properties and the White Beeswax BP is added to help stiffen the oint. iodine. Anionic Emulsifying Wax BP Emulsifying ment. Aquosum BP (Hydrous of the active ingredient to be incorporated (i. Ointment BP neous mixture of the Hard Paraffin BP and the Cationic Cetrimide Cetrimide White Soft Paraffin BP. There with a sterol type of emulsifying agent such as: are a number of different molecular weight macrogols and by combining various ones a product with * beeswax the consistency of an ointment can be produced.e.1 Examples of different emulsifying bases Cetostearyl Alcohol BP 50 g Ionic nature of Emulgent example Base produced The Cetostearyl Alcohol BP is added to the hydro. with water and therefore ‘washable’. There are three types Macrogol bases are used with local anaesthetics of emulsifying base – anionic. The name applied to ous solutions to form water-in-oil (w/o) emulsions. British Pharmacopoeia and Olive Oil BP was replaced by Liquid Paraffin BP. emulsifying agent (oil in water) to make them miscible * They are non-irritant to the skin. * wool fat (lanolin).1). including phe- charge (i. hydrophilic substances These bases are capable of absorbing water and aque. Olive Oil BP was an accepted ingredient in Ung. soya or maize Emulsifying Wax BP Emulsifying oil. They are easy to remove from the skin and therefore also make suitable Examples include Macrogol Ointment BP. that are non-irritant to the skin. almond oil. Emulsifying bases * They do not hydrolyse or deteriorate. * They are easily washed off. it has a negative. them in the BP is ‘macrogols’ and the solid grades They consist of one or more of the paraffins combined (1000 and above) are used as ointment bases. olive oil. respectively) (Table 5. These are anhydrous bases that contain sufficient * They do not support mould growth. exudates. These ingredients help to produce a homoge. the reduce the antimicrobial properties of quaternary choice of base is determined by the chemical nature ammonium compounds such as cetrimide. Emulsifying Wax BP Emulsifying Fats and fixed oil bases Ointment BP Ointment bases can include oils of vegetable origin Non-ionic Cetomacrogol Cetomacrogol such as arachis oil. which can absorb about 50% Macrogols have several advantages: of its weight of water (NB patients can become sensitised to lanolin) * They are water miscible and therefore allow * wool alcohols (These are the emulsifying medications to mix with skin secretions and component of wool fat obtained by fractionation). the formu- dictates which type of emulsifying base is appropriate lation was updated in the Sixth Addendum to the 1932 to use). For example. light Ointment BPC and high temperatures and turn rancid. nols.e. Such oils can decompose on exposure to air. potassium iodide and the salts of silver. More significantly they also All of these bases are miscible with water. * They are non-occlusive. Water-soluble bases Absorption bases Polyethylene glycols are stable. Extemporaneous dispensing | 79 White Beeswax BP 20 g Table 5. positive or no charge. mercury and bismuth. Because of the problems of rancidity overall charge on an ingredient to be incorporated that and because it facilitates bacterial growth. Wool Alcohols Ointment BP and Simple Ointment BP. it is the Ointment BP). cationic and non-ionic – such as lidocaine but their use is limited because they and the ionic nature of the base is determined by its are incompatible with many chemicals. in the 1932 British Pharmacopoeia. Examples of this type of ointment base include * They are non-staining to clothes or bed linen. Preservatives * It has a tendency to stick to the mould. and is most commonly obtained as a by-product in the manufacture of cocoa. * Its softening point makes it unsuitable for use in unsuitable containers or inadequate storage con- hot climates. * either melt after insertion into the body or dissolve Aqueous bases in (and mix with) any rectal or vaginal fluid The most commonly encountered aqueous base is (ideally the melting range should be slightly lower Glycerin Suppository BP base. It is the solid fat obtained from alone as they are small batch productions and not the crushed and roasted seeds of Theobroma cacao intended for long-term storage. Synthetic materials used in packaging bases also become very brittle if cooled too quickly. diglycerides and monoglycerides. * free from unpleasant odours . It has many of the prop- erties of an ideal suppository base but has largely Preservatives been replaced by synthetic alternatives for various Antimicrobial preservatives are added either to kill reasons: or slow down the growth of microorganisms. When prepar- ing suppositories extemporaneously the synthetic fats Fatty bases are the most commonly used bases. and invariably the Theobroma Oil BP is a yellowish-white solid that suppository consists of the active ingredients and base smells like chocolate. hardening agents or viscosity modifiers and preservatives. resulting from unsatisfactory production processes. and as a suppository base it exerts a local pur- * be non-toxic and non-irritant gative action and therefore its usefulness is limited * be compatible with any medicament and release it through premature evacuation of the bowel. compounding process and product use. ditions. Micro- organisms may be present in ingredients used to pre- * It is particularly susceptible to physical changes pare the product or may be introduced during the with overheating. is an ideal supporting medium for many micro- organisms. * readily soluble at the concentration used ing point and setting point is small (generally 1. and systems thetic bases when melted increases the risk of sedimen. such as emulsifiers. They are pre- pared by hydrogenating suitable vegetable oils and * active at low concentrations with rapid examples include Hard Fat BP. rubbers and other the problem of sedimentation is minimal. The use of this base is than 37 C as body temperature may be as low as limited by the incompatibility of gelatin with medica- 36 C at night) ments. * compatible with a wide number of medicaments The drawback is that the low viscosity of the syn. * As a natural product it tends to go rancid on Aqueous preparations are the most susceptible to storage owing to oxidation of the unsaturated microbial contamination as an aqueous environment glycerides. which are never added to obscure microbial contamination needs lubricating before use. of suppositories.5–2 C) * compatible with plastics.80 | Pharmaceutical forms and their preparation Suppository and pessary bases Therefore setting must not be accelerated by The ideal suppository or pessary base should: refrigeration. Synthetic fats The ideal antimicrobial preservative has the fol- Synthetic fats have all the advantages of Theobroma lowing properties: Oil BP but none of the disadvantages. * be stable to heating above the melting point Other additives are used in the mass manufacture * be stable on storage and resistant to handling. * active and stable over a wide temperature range tation of the active ingredient during the preparation * active and stable over a wide pH range of the suppository. readily Macrogol bases are also used as suppository bases * be easily moulded and removed from the mould for proprietary products. but as the difference between melt. which is a mixture of bactericidal and fungicidal action triglycerides. not disagreeable) antimicrobial preservative between pH 4 and 8.001–0.e. * Thiomersal – Used as an alternative to of Blackcurrant Syrup BPC and Liquid Glucose BP. Widely used to preserve pharmaceutical form. ophthalmic preparations (0. Extemporaneous dispensing | 81 * no unpleasant taste * Ethyl hydroxybenzoate – Active as an * suitable colour (i. * Butyl hydroxybenzoate – Antimicrobial Quaternary ammonium compounds preservative active over a wide pH. antiseptic.05–0.0% v/v) and a disinfectant (10% v/v). phenyl mercuric acetate in acidic preparations. Used commonly 0.002% w/v) concentrations of 0.15%). * Phenyl mercuric nitrate – Used in preference to useful as it can be used with gelatin and vegetable gums.01–0.3% v/v.2% in oral and topical and also used as a spermicide in spermicidal jellies pharmaceutical formulations. use owing to toxicity. solubilising varying concentrations dependent upon the agent and wetting agent.02% w/v).2% w/v. * non-carcinogenic * Propyl hydroxybenzoate – Used in varying * non-irritant and non-sensitising at the concentrations dependent upon the concentration used. In higher concentrations aqueous solution. In . It has both bacteriostatic and Alcohols fungistatic activity and is used in a number of preparations in varying concentrations * Benzyl alcohol – Antimicrobial preservative (0. * Cresol – Used as an antimicrobial preservative in antibacterial preservative than alcohol. phenyl mercuric nitrate as it is more soluble. Only suitable for antimicrobial preservative in ophthalmic and products not intended for oral route of parenteral formulations (0. * Phenol – Mainly used as a preservative in some topical formulations (1% v/v). Shows some antimicrobial Only suitable for products not intended for oral activity and is used as a disinfectant as a 70% v/v route of administration. attractive. parenteral products (0. (2. * Isopropyl alcohol – Not recommended for oral preservative in concentrations of up to 0. * Phenoxyethyl alcohol – Usually used as an concentrations 0. * Sulphurous acid – Used in food preservation as it Used in eye drops and parenteral formulations shows low toxicity in the concentrations used. It is particularly (0.25–0. pharmaceutical form.001–0. as an antimicrobial preservative (0. benzalkonium chloride and other phenyl mercuric preservatives. in eye drops and parenteral formulations as an * Sorbic acid – Antimicrobial activity shown in antimicrobial preservative (0. * Ethyl alcohol (ethanol) – Antimicrobial Phenols preservative (10% v/v) also used as a * Chlorocresol – Used as an antimicrobial disinfectant (60–90% v/v).02% w/v). having a broad spectrum of antimicrobial activity but being most * Benzalkonium chloride – Antimicrobial effective against yeasts and moulds. * non-toxic at the concentrations necessary for * Methyl hydroxybenzoate – Active as an preservative activity antimicrobial preservative between pH 4 and 8. disinfectant. Used in preservative.5% v/v) and in administration. It is a more effective it is an effective disinfectant.1% w/v in solutions.001–0.15–0. Acids Mercurials * Phenyl mercuric acetate – Used in preference to * Benzoic acid – Used in varying concentrations dependent upon the pharmaceutical form.002% Pharmaceutical applications include preservation w/v).5% w/v) although it has Hydroxybenzoates also been used in topical preparations. oil-soluble vitamins. Examples include: sweetener. Often used in conjunction with butylated hydroxytoluene and the alkyl Antioxidants gallates and chelating agents such as citric acid. rubbers and other Miscellaneous examples materials used in packaging * free from unpleasant odours * Bronopol – Antimicrobial preservative (0. solvent and chain reaction in auto-oxidation. attractive not disagreeable) * Chlorbutol – Used primarily as an antimicrobial * non-toxic at the concentrations necessary for preservative in ophthalmic or parenteral preparations.1% w/v).e.1% w/v.002– * active at low concentrations 0. Any antioxidant included in oils. its inclusion in most 30% v/v). and is formations encountered in extemporaneous dispens- particularly used to prevent loss of activity of ing are summarised in Table 5.5. * Propylene glycol – Used as an antimicrobial * Alpha-tocopherol acetate – Although this acts as preservative for solutions and semi-solids (15– an antioxidant. antiseptic.0 %). These are thought to block chain reactions by reacting * Glycerol – In addition to its action as an with free radicals. Also The properties of an ideal antioxidant are similar possess some antimicrobial activity against both to those of an ideal antimicrobial and include: Gram-negative and Gram-positive bacteria and .82 | Pharmaceutical forms and their preparation nasal and ophthalmic formulations (0. Antioxidants can be grouped according to their * Chloroform – Chloroform (0. for example. oil-soluble vitamins.25% v/v) usually mechanism of action. included in solutions or mixtures designed for oral use in the form of chloroform water (see Chapter Antioxygens 2.01– * no unpleasant taste 0. page 32). The decomposition of pharmaceutical products by * Butylated hydroxytoluene (BHT) – Used to oxidation can be retarded by the addition of antiox. propyl and octyl gallate) – formulation itself and not produce unwanted changes Primarily used to prevent rancidity in fats and oils. and systems * Cetrimide – Used as an antimicrobial preservative * active and stable over a wide temperature range in eye drops (0. cament in the product and also compatible with the * Alkyl gallates (dodecyl. in that formulation.005% w/v) and as an antiseptic in * active and stable at a range of pH aqueous solution (0.2.002–0.1–1. pharmaceutical formulae is as a source of * Sucrose – When sugar is present in high vitamin E. humectant.005% w/v).02% w/v in combination with thiomersal * compatible with a wide number of medicaments 0. Its antimicrobial activity tends to be antioxidant activity * non-carcinogenic bacteriostatic rather than bactericidal and its * non-irritant and not sensitising at the action is markedly reduced above pH 5. Used in concentrations up to 0. antimicrobial activity similar to that of the parabens (hydroxybenzoates). * readily soluble at the concentration used * compatible with plastics. It is used to prevent The commonly used preservatives used in different or delay oxidative rancidity of fats and oils. * Chlorhexidine – Antimicrobial agent and concentration used. They provide the necessary elec- antimicrobial preservative (>20% v/v) glycerol is trons and easily available hydrogen ions to stop the also an emollient. * Butylated hydroxyanisole (BHA) – In addition to fermentation is prevented because of the resultant its antioxidant properties this also has some osmotic pressure. concentrations (67%) in. * suitable colour (i. elixirs. and particularly to prevent loss of activity of the product must be compatible with the active medi. prevent or delay oxidative rancidity of fats and idants (reducing agents). 25% v/v) Ammonia and Ipecacuanha Mixture BP Included as Chloroform Water BP or Double Strength Chloroform Water BP Glycerol Diamorphine Linctus BPC Methyl hydroxybenzoate Streptomycin Elixir Paediatric BPC Sucrose Paediatric Chloral Elixir BP Solutions for external use Alcohol Chloroxylenol Solution BP 1988 Soap Liniment BPC Benzalkonium chloride Phosphates Enema BPC Chlorbutol (0.25% v/v) Sodium Chloride Mouthwash BP Included as Chloroform Water BP or Double Strength Chloroform Water BP Glycerol Sodium Bicarbonate Ear Drops BPC Suspensions for oral administration Benzoic acid (0.1% w/v) Liquid Paraffin Emulsion BP 1968 Chloroform (0.25% v/v) Liquid Paraffin Emulsion BP 1968 Included as Chloroform Water BP or Double Strength Chloroform Water BP Creams and external emulsions Cetrimide Cetrimide cream BP 1988 Chlorocresol Cetomacrogol Cream (Formula A) BP Dimethicone Cream BPC Buffered Cream BPC Hydroxybenzoates Cetomacrogol Cream (Formula B) BP Phenoxy ethyl alcohol Aqueous Cream BP Oily Cream BP .5% w/v) Ephedrine Nasal Drops BPC 1973 Chloroform (0.1% w/v) Paediatric Kaolin Mixture BP1980 Chloroform (0.2 Common preservatives used in extemporaneous dispensing along with examples of extemporaneous preparations containing them Pharmaceutical formulation Antimicrobial preservative used Examples Solutions for oral administration Alcohol Phenobarbital Elixir BPC Benzoic acid (0. Extemporaneous dispensing | 83 Table 5.25% v/v) Magnesium Trisilicate Included as Chloroform Water BP or Double Mixture BP 1988 Strength Chloroform Water BP Suspensions for external use Alcohol Compound Sulphur Lotion BPC 1973 Liquefied phenol Calamine Lotion BP Emulsions for oral administration Benzoic acid (0.1% w/v) Kaolin Paediatric Suspension BP Chloroform (0. butylated hydroxytoluene concentrations of 0. of the reaction of the antioxidant with peroxides to * Tartaric acid – Also used as an acidifier and form free radicals). in higher con- * Sodium citrate – Also used as an alkalising agent centrations the antioxidant effect may be less because and buffering agent. It is also important to ensure that the * Citric acid – Also used as an acidifying agent. As an antioxidant it is used in concentrations of 0.01–0. nounced variations of pH during use and storage. auto-oxidation. antioxidant synergist it is used in concentrations Concentration of the antioxidant of 0. It is widely used in conjunction with bicarbonates as the acidic component of effervescent granules and tablets. . They protect a drug until they antioxidant added to the formula should be preferen- themselves are used up or until all the oxygen in the tially soluble in the oily phase. is not recommended in preparations for oral administration to children and babies. Generally the more antioxidant added. As an product.005–0. The addition of an container is used up. As an Buffers antioxidant synergist it is used in concentrations Buffers are often added to solutions to prevent pro- of 0. the oily (lipid) medicament and therefore can be used if oxidising phase may be susceptible to oxidation and therefore an agents are present. Examples include: atmospheric oxygen. which is Chelating agents especially true of plastic and rubber closures. The concentration of antioxidant used is normally * Disodium edetate (disodium dihydrogen determined by previous experience with that antioxi- ethylenediaminetetra-acetate dihydrate–EDTA) – dant. In a suspension. For example. flavour enhancer. preparations such as syrups.002–0. Sodium sideration must be given to the likelihood of adsorp- metabisulphite also has some preservative tion of the antioxidant onto particles of the drug or properties and is often used to preserve oral interaction with the suspending agent.5%. Packaging * Sodium sulphite – Used in preference to sodium The antioxidant chosen must not react with the pack- metabisulphite in alkaline preparations.01–0. Mainly used in gels. Atmospheric oxidation is con- trolled by the use of antioxidants such as butylated * Ascorbic acid – Used as an antioxidant in hydroxyanisole (BHA).1%.84 | Pharmaceutical forms and their preparation also fungi.1%. Reducing agents are therefore antioxidant is also important as some of the emulsify- also useful in blocking chain reactions that occur in ing agents themselves can be subject to oxidation by the auto-oxidation of drugs. pastes. suppositories and pessaries. con- preparations that are acidic in nature. propyl or dodecyl gallate. the Used in concentrations of 0. They have been reported to give an ‘off’ Choice of antioxidant flavour to corn and cottonseed oils when used as There is no perfect antioxidant as all have their lim- an antioxidant. These are * Sodium metabisulphite – Used in oral. and topical formulations.01–0. The choice is determined by a number of internal and external products but their inclusion factors.01%. in two-phase Reducing agents are more readily oxidised than the systems such as emulsions and creams. (BHT) or ethyl. antioxidant is incorporated evenly throughout the buffering agent and flavour enhancer. parenteral also often used as antioxidants in ointments. greater the antioxidant effect (however. aging as its effectiveness can be reduced if it is adsorbed by the container or the closure. Formulation The type of formulation may well influence the effec- Reducing agents tiveness of an antioxidant. These enhance the effects of antioxidants but have Time of addition of the antioxidant little use as sole agents as they work by chelating It is important to add the antioxidant as early as pos- with heavy metal ions which often catalyse auto- sible in the preparation of a product to help slow down oxidations. Alkyl gallates can be used for itations.02%. 82 8.8 5.4 increase the viscosity of the vehicle and therefore slow down sedimentation rates. Extemporaneous dispensing | 85 Buffers dissolve in the solvent and then resist changes Table 5. Acacia 9.16 1. The pH and buffering capacity required required for a given pH value will determine the choice of buffer.4 their potential toxicity when systemically absorbed.68 5. 7.72 13.1 4.48 15. citrates.54 2.1.73 2.0 Borate buffers 6.28 1.8 3.0 21.4 branches of some species of acacia tree.0 4.3 Quantity of boric acid. pH Sodium acid Sodium Sodium chloride nates.4) (Table 5.5) and Hypromellose Eye Drops BPC 1973 (pH 7.4 2.0 0.4 11.6 The amount of suspending agent used in any given 7. lactates. A suspending agent is intended to 8. gluconates and phosphate phosphate to make tartrates. Borates have been used for external prod.7 Thickening and suspending agents 7.5 4.8 12.9 A borate buffer (boric acid/borax) pH range 6.2 14.9 Natural polysaccharides 8. The pH of most bodily fluid is 7.4 Quantity of sodium acid phosphate. phosphates.5–8.58 10.20 0.7 10.4 6.7 4.6 formulation depends on the volume of vehicle being thickened.78 2.4 5.69 2.6 5.7 is normally used in combination with tragacanth and . It does not vary with the amount of powder 8.7 4.7 4.37 1.2 5.2 8.8 5.1 16.66 1.0 9.1 in suspension.3).91 2.92 3.57 2.2 11.3 7.6 6.5 22. in pH should an acid or an alkali be added to the sodium phosphate and sodium chloride that is formulation.4 and therefore 6.4 2. Borate buffers are not included in topical prepara.9 4.8 Acacia BP This is a natural gummy exudate from the stems and 8.7 7.1 19.5 in the preparation.60 2.1 lage of acacia in water is prepared by using acacia gum 4 parts by weight and water 6 parts by volume. This outcome could also be 8.82 2. 7. Most pharmaceutical buffers are based on carbo.5 is used to buffer Neomycin Eye Drops BPC 1973 (pH 6.2 11.5 tions used on abraded skin or membranes because of 7.3 8.4).2 3.2 Table 5.2 membranes.2 8.5) and 6.6 8.87 2. borax and sodium chloride that is required for a given pH value Phosphate buffers pH (25 C) Boric Borax Sodium chloride to A phosphate buffer (sodium acid phosphate/sodium acid (g/L) (g/L) make iso-osmotic (g/L) phosphate) pH range 4.8–9.7 Prednisolone Sodium Phosphate Eye Drops BPC 1973 (pH 6.06 6.51 1.46 1.0 2. is used to buffer Chloramphenicol Eye Drops BP 1993 6. 8. 6.3 achieved by decreasing the particle size of the powder 8.6) (Table 5.1 1. (g/L) (g/L) iso-osmotic (g/L) ucts but not in those intended for abraded skin or 5. A viscous muci- 9.8 9.5 4.15 2.3 4.7 1.3 4.24 17.8 (pH 7. 7.9 9.30 4.2 9.5 7.1 this is the pH for which most products will be buffered.03 0.96 11.1 8. mainly used in products intended for external use although some grades of this product can be used internally. and often absorb many times their weight in water. which indi. Compound Tragacanth Powder BP is a suit- Clays able suspending agent for products for internal use but A number of naturally occurring clays are used as because of the high sucrose content it is unsuitable for thickening agents. depending on the polymer used. Methylcellulose is suitable mixtures include polysorbates and sorbitan esters. used for pharmaceutical manufacture be sterilised The appropriate quantities of Tragacanth BP and prior to use as a suspending agent. Wetting agents used for internal used as thickening agents. The colour may make it unsuitable for use in some products. This is because air becomes trapped in Semi-synthetic polysaccharides the solid particles and prevents them from being dis- Methylcellulose BP persed through the vehicle. the quantity of suspending agent is not Synthetic thickeners given on a prescription and so the compounder Synthetic thickeners have been developed as standar- needs to know how much suspending agent to dised products that can easily be reproduced.2 g Tragacanth BP powder for 100 mL Carbomer suspension * The main advantage with carbomer is that it is used in 2 g Compound Tragacanth Powder BP for very low concentrations. Because these clays hydrate easily external products as it renders them too sticky.86 | Pharmaceutical forms and their preparation starch in Compound Tragacanth Powder BP (Acacia BP To form a suspension 0. although acacia and tragacanth can also be used. and also because they are natural products Wetting agents may also be added to aid suspension of there is a greater chance of microbial contamination. . for products intended for both internal and external use. when it is combined not support microbial growth neither do they inhibit with water it forms a viscous liquid or gel depending it. added this is adsorbed at the solid/liquid interface. The name forms at the liquid/air interface.4%. A film of unwettable solid Methylcellulose is a methyl ether of cellulose. Tragacanth BP 15%. Tragacanth can be used as clays themselves are prone to contamination with a sole suspending agent. This use. making the particles have more affinity for the sur- Methylcellulose 2500 and methylcellulose 4500 are rounding vehicle. Bentonite BP may be be used for external as well as internal products.5–2% methylcellulose is 20%. Some powders tend to float on the surface of the preparation.1–0. It is Key Skill 5. Tragacanth BP they produce gels of varying thickness depending on This is the dried gummy exudate from some species of the concentration of clay used. It is 100 mL suspension. cates the approximate viscosity of a 2% solution. Often. powders. To form a suspension for external use 2–3% of suspensions Bentonite BP is required. * 0.1 Appropriate quantities used in suspensions for external use such as calamine of tragacanth to use to form lotion. The on the concentration used. Starch BP 20% and Sucrose needed. The main problem with natural products is that their natural variability can cause differences between Wetting agents batches. normally 0.1. This is a very pale buff-coloured powder. therefore a preservative must also be added. If a wetting agent is ‘methylcellulose’ is followed by a number. overcomes the problem of variability of naturally occurring suspending agents. Compound Tragacanth Powder BP to use to form sus- Bentonite BP pensions are listed in Key Skill 5. Like acacia. and as it is less sticky it may microbial spores (for example. BP 45%). It is therefore essential that any clays powders. contaminated with Clostridium tetani) as they are nat- Tragacanth is used to suspend heavy insoluble ural products. Although these clays do the Astralagus shrub. These are termed anionic. water-in-oil emulsions and is chosen in preference to Wool Fat BP. Examples include: non-toxic and non-irritant. . Extemporaneous dispensing | 87 Wetting agents suitable for products for external use ionic emulsifying waxes. triethanolamine oleate * soaps of divalent and trivalent metals. not affecting the efficacy of the product. a thick- ening agent. page 135). sodium lauryl sulphate * Emulsifying agents amine soaps. for example cetri- bules. cationic and non. Colourings Colourings are used in pharmaceutical preparations to Wool Fat BP increase the acceptability of a product to a patient and This is obtained from sheep wool. Some are oil-soluble Methylcellulose BP stabilising water-in-oil (w/o) emulsions. For example. It is made up of the also to ensure a consistent appearance of a product fatty acid esters of cholesterol and other sterols and that may have ingredients that can vary slightly in alcohols. despite its emulsion stabiliser. as emulsions made with Wool Alcohols BP do not have an objectionable odour in hot weather. 8. water emulsions for external use. Because of the low viscosity of any emulsions mide and benzylkonium chloride. It is a good emulsifying agent for extemporaneous dispensing are described in Table 5. Many of the substances described as thickeners in the formulation of suspen. internal use (Table 5. These are synthetic materials.6). e. water-soluble and stabilise oil-in-water (o/w) emul- sifying agents and emulsion stabilisers. sodium sions also act as emulgents. The introduction of although it is similar to human sebum.g. It is used mainly as an inconsequential degradation product that. e. as in Sulphur Compound ents.g.5. is often also added as an emulsion Non-ionic surfactants stabiliser. Generally the colorant of choice is These are the main emulsifiers used in external pro. tragacanth. This is the most widely used emulsifying agent for extemporaneously prepared oral emulsions. * alkyl sulphates. slowing down any coalescence of the glo. Acacia Cationic surfactants stabilises emulsions by forming a film around each Usually these are used in the preparation of oil-in- oil globule. Both water-in-oil and oil. may hamper Emulsifying waxes patient compliance. appearance from batch to batch. To help prevent this. creaming may occur (see Chapter also have antimicrobial activity. others are Some grades of methylcellulose can be used as emul. * alkali metal and ammonium soaps.g. cetostearyl alcohol and a surface active agent Lotion BPC 1973. it can cause a colour can also mask an unattractive colour of an sensitisation in some people. or sodium lauryl sulphate. sions. Acacia BP calcium oleate. for example Oily Calamine Lotion BPC Emulsifying agents for internal use should ideally be 1973. One problem with this as an emulgent is that. determined by the flavour of the product if it is for ducts.g. This is made by treating Wool Fat BP with alkali and separating the fraction containing cholesterol and Three types of emulsifying wax encountered in other alcohols. * glycol and glycerol esters * polysorbates Wool Alcohols BP * sorbitan esters. Each consists of two ingredi- include quillaia tincture. Cationic surfactants formed using acacia. (surfactant). Emulsifying agents and emulsifying Anionic surfactants waxes Anionic surfactants are often used to produce oily lotions. e. Colourings and flavourings as is often the case with Wool Fat BP. stearate in-water emulsions will need an emulsifying agent. Examples include: 2% of Methylcellulose 20 is used in Liquid Paraffin * fatty alcohol polyglycol ethers Oral Emulsion BP. e. 88 | Pharmaceutical forms and their preparation Table 5.5 Composition of three types of emulsifying wax Product Oil-soluble Water-soluble Ratio CSA/SAA Notes component component Cetomacrogol Emulsifying Cetostearyl Cetomacrogol 8:2 Cetomacrogol 1000 is a condensate of cetyl Wax BP (non-ionic) Alcohol BP BP and stearyl alcohol with ethylene oxide and is non-ionised Cetrimide Emulsifying Wax BP Cetostearyl Cetrimide BP 9:1 On dissociation the 'cetyl trimethyl (cationic) Alcohol BP ammonium' group of cetrimide is the cation Emulsifying Wax BP (anionic) Cetostearyl Sodium Lauryl 9:1 On dissociation the 'lauryl sulphate' group of Alcohol BP Sulphate BP sodium lauryl sulphate is the anion CSA, cetostearyl alcohol; SAA, surface active agent. Colorants can also be added to products for exter- good colour and an even distribution. To obtain nal use to indicate that they should not be taken inter- the maximum colour carmine should be dissolved nally, for example the addition of colouring to in a small quantity of strong ammonia solution mineralised methylated spirit. In hospitals different before triturating with the powder. The colouring antiseptics may be coloured according to their use matter is precipitated in acidic solution. (e.g. disinfection of skin, instruments, syringes, etc.). * Chlorophyll – The green colouring matter in Colourings used in pharmaceutical preparations plants. Its principal use is as a colouring agent for are either natural agents or synthetic dyes. Natural soaps, oils and fats. agents include: * Cochineal – Made from the dried bodies of the female insect Dactylopius coccus (or the crushed * Caramel (burnt sugar) – Prepared by heating a eggs in the case of cochineal extract). suitable water-soluble carbohydrate with or * Saffron – The dried stigmas and tops of the styles without a suitable accelerator until a black viscous of Crocus sativus. Saffron exerts no therapeutic mass is formed. It is then adjusted to the required effects and is used as a colouring and flavouring in standard by the addition of water and strained. some pharmaceutical products. Caramel is capable of producing a wide range of * Turmeric – The dried rhizome of Curcuma colours, from a pale straw colour to dark brown. domestica. * Carmine – A preparation of cochineal (see below) containing about 50% carminic acid. Carmine is The choice of colorant can be affected by the used for colouring ointments, tooth powders, country of use, as different countries have different mouthwashes, dusting powders, medicines and legislation with regard to colorant use. This problem other preparations. If in solid form prolonged is exacerbated by the various synonyms used for trituration with a powder is necessary to obtain a the same dye. For example, amaranth, a common Table 5.6 Flavourings associated with each of the different colourings used in pharmaceutical preparations intended for internal use Colour Flavour Red Cherry, strawberry, raspberry Yellow Citrus fruits, banana Green Mint flavours Extemporaneous dispensing | 89 ingredient for extemporaneous dispensing, is also acceptability to the patient. Masking an unpleasant known as: flavour may prevent the feeling of nausea or the inci- dence of vomiting. Flavourings are often derived from * Bordeaux S natural products and are available in a number of * CI Acid Red 27 formulations for use in the extemporaneous prepara- * CI Food Red 9 tion of products. These include the aromatic waters, * Colour Index Number 16185 (by Society of Dyers concentrated extracts, syrups or spirits. Often the and Colourists and the American Association of addition of syrup will be sufficient to mask unpleasant Textile Chemists and Colorists) tastes. * E123 (Council of European Communities) Syrup (a solution of sucrose in water) may be used * FD and C Red Number 2 (by USA Food, Drug and as a co-solvent or as a solvent in its own right in a Cosmetics Act). number of oral medicines, e.g. elixirs and linctuses. It Generally within the UK, the E number specification is acts as a sweetening agent to mask unpleasant-tasting most commonly used. ingredients. Unfortunately it has the disadvantage of Examples of colours permitted for use in the UK promoting dental decay. It is also unsuitable for dia- are listed in Table 5.7. betic patients who need to monitor their carbohydrate The use of colorants for oral medication is falling intake. out of favour because of the association of additives Examples of flavoured syrups that are often used with rare allergic reactions and cases of hypersensitiv- to mask unpleasant tastes along with examples of pre- ity and hyperactivity. Tartrazine, for example, has parations that contain them are listed in Table 5.8. been associated with hypersensitivity reactions and Flavouring is particularly important in paediatric intolerance, particularly in those sensitive to aspirin. formulations, as the correct choice of flavouring can Its use in medicinal preparations is therefore diminish- ensure patient compliance. In addition to providing ing and any official formula calling for the addition of sweetness and flavour, the texture of the product can tartrazine may be prepared without it if sensitivity may also be enhanced, giving a more pleasant sensation in be an issue with the intended patient. the mouth. In addition to the flavoured syrups described Flavourings above, various other ingredients are used to flavour Liquid preparations for oral use are usually flavoured pharmaceutical preparations. These are also listed and occasionally coloured to improve their in Table 5.8. Table 5.7 Examples of permitted colours for inclusion in pharmaceutical products in the UK E numbers Colour range Examples 100–110 Yellows E101 Riboflavin E102 Tartrazine E110 Sunset Yellow 120–128 Reds E120 Cochineal carminic acid E123 Amaranth E127 Erythrosine 131–133 Blues E131 Patent Blue V 140–142 Greens E140 Chlorophylls E142 Acid Brilliant Green 150–155 Black and browns E150 Caramel E153 Carbo medicinalis vegetabilis (charcoal) 170–175 Metallic E172 Iron Oxides 90 | Pharmaceutical forms and their preparation Table 5.8 Flavourings and examples of preparations in which they are used Example of use Flavoured syrups Blackcurrant Syrup BP Ipecacuanha and Squill Linctus Paediatric BPC Paediatric Chloral Elixir BPC Ginger Syrup BP Rhubarb Mixture Paediatric BP Sodium Bicarbonate Mixture Paediatric BP Lemon Syrup BP Codeine Linctus BP Orange Syrup BP Ferrous Sulphate Mixture Paediatric BP Raspberry Syrup BP Kaolin Mixture Paediatric BP Tolu Syrup BP Squill Opiate Linctus BP Methadone Linctus BP Aromatic waters Concentrated Anise Water BP Ammonia and Ipecacuanha Mixture BP Belladonna and Ephedrine Mixture Paediatric BP Concentrated Cinnamon Water BP Chalk Mixture Paediatric BP Concentrated Dill Water BP Sodium Bicarbonate Mixture Paediatric BP Concentrated Peppermint Water BP (latterly replaced by Kaolin Mixture BP Concentrated Peppermint Emulsion BP) Magnesium Carbonate Mixture BP Magnesium Trisilicate Mixture BP Double Strength Chloroform Water BP Although its primary use in extemporaneous dispensing is as a preservative, it is also considered to provide a pleasant flavouring Spirits Compound Orange Spirit BP Belladonna Mixture Paediatric BP Ferric Ammonium Citrate Mixture Paediatric BP Ipecacuanha and Squill Linctus Paediatric BP Lemon Spirit BP Diabetic Codeine Linctus BP Potassium Citrate Mixture BP Sodium Citrate Mixture BP Concentrated extracts Liquid Liquorice Extract BP Ammonia and Ipecacuanha Mixture BP Ammonium Chloride Mixture BP Ipecacuanha and Morphine Mixture BP Choice of flavouring prefer slightly acidic flavouring and older people The choice of flavouring is affected by a number of often find mint or wine-flavoured products factors: preferable. * The use of the product – Products intended for the * The intended recipient – Children generally prefer relief of indigestion, for example, are often fruit or sweet flavours, whereas adults tend to flavoured with peppermint. This is because Extemporaneous dispensing | 91 traditionally mint has been used for its Quantities of flavourings to use carminative effect. Nowadays, although the Table 5.9 lists suggested doses of some suitable fla- action of the product may be dependent on a vourings for extemporaneously prepared products. totally different active ingredient, peppermint Note the inclusion of Concentrated Peppermint flavouring is added because the smell and taste of Emulsion BP, which has superseded Concentrated mint is strongly associated with antacid action. Peppermint Water BP as the flavouring of choice. * The type of unpleasant taste to be masked: In the absence of a dosage guide for individual fla- a A bitter taste can be masked by anise, vourings, another way to decide on the amount of fla- chocolate, mint, passion fruit, wild cherry. vouring to include in a product is to compare the The effect of a bitter aftertaste has also been quantities used of the flavouring of choice in official reduced by addition of flavour enhancers products. For example, many indigestion mixtures have such as monosodium glutamate. a peppermint flavouring, and in the absence of any other b Saltiness can be counteracted by apricot, data concerning the quantity of Concentrated Pep- butterscotch, liquorice, peach or vanilla. permint Emulsion BP to use to safely flavour a magistral Butterscotch and caramel combined have formula, one could compare the amounts used in for- been found to be particularly successful in mulae such as Magnesium Trisilicate Mixture BP and masking the taste of salty drugs. Kaolin Mixture BP, where the formulae would suggest c A sour taste can be masked by citrus fruits, using 25 mL of Concentrated Peppermint Emulsion BP liquorice or raspberry. in 1000 mL of mixture. Therefore if you use Con- d Sweetness can be toned down using vanilla, centrated Peppermint Emulsion BP in the same propor- fruits or berries. tions in a magistral formula as the proportions in an official formula the dose you use is likely to be safe. Other additives used to affect flavour include: * Citric Acid BP – This obscures some bitter tastes Storage and labelling requirements and has the added advantage of improving the ability of citrus flavours to mask acid tastes. Storage * Menthol BP and Peppermint Oil BP – These have a All products dispensed extemporaneously require slightly anaesthetic action locally and therefore some form of additional storage instructions to be numb the taste buds. detailed on the label. This information can be the * Sodium Chloride BP and Sodium Citrate BP – addition of just a product expiry date through to a These help to reduce bitterness. number of important additional auxiliary labels. The summary list given in Table 5.10 can be used The traditional flavourings previously highlighted as a guide in the absence of any guidance from the are obtained from natural products. Numerous other official pharmaceutical texts, but it should be used as flavourings have been produced synthetically and as a guide only – any information on additional labelling these tend to be a cheaper alternative to the natural or expiry dates in the official texts will take prece- products it is the synthetic flavours that tend to be dence. The suggested expiry dates in Table 5.10 are employed commercially. based on historical practice. Nowadays, it is common Further information on both colourings and fla- to assign a maximum of a two-week discard to any vourings can be found in the following pharmaceutical extemporaneously prepared product, and consider- texts: ation should always be given to assigning a shorter discard date. 1 The British Pharmacopoeia (current edition). 2 Martindale – The Extra Pharmacopoeia (current edition). General principles of labelling 3 Wade A, Weller P J (ed.) 1994, Handbook of Every pharmaceutical preparation requires a label to Pharmaceutical Excipients. The Pharmaceutical be produced before the product can be dispensed or Press, London. sold to the patient. The accuracy of the label is of 92 | Pharmaceutical forms and their preparation Table 5.9 Guide to suggested doses of different flavourings commonly used in pharmaceutical products Flavouring Suggested dose Blackcurrant Syrup BP 5–10 mL Concentrated Anise WaterBP 0.3–1 mL Concentrated Caraway Water BP 0.3–1 mL Concentrated Cinnamon Water BP 0.3–1 mL Concentrated Dill Water BP 0.3–1 mL Concentrated Peppermint Emulsion BP 0.25–1 mL Concentrated Peppermint Water BP 0.25–1 mL Double Strength Chloroform Water BP 5–15 mL Ginger Syrup BP 2.5–5 mL Lemon Syrup BP 2.5–5 mL Liquid Liquorice Extract BP 2–5 mL Orange Syrup BP 2.5–5 mL Raspberry Syrup BP 1 Ml Tolu Syrup BP 2–10 mL Table 5.10 Guide to auxiliary labels and discard dates for extemporaneous preparations Preparation Container Important auxiliary labels Suggested discard date Applications Amber fluted bottle with CRC For external use only 4 weeks Capsules Amber tablet bottle with CRC See BNF for advisory labels 3 months recommended for active ingredient Creams and gels Amber glass jar or collapsible For external use only 4 weeks metal tube Dusting powders Plastic jar, preferably with a For external use only 3 months perforated, reclosable lid Not to be applied to open wounds or raw weeping surfaces Store in a dry place Ear drops Hexagonal amber fluted glass For external use only 4 weeks bottle with a rubber teat and dropper closure Elixirs Plain amber medicine bottle 4 weeks with CRC Extemporaneous dispensing | 93 Emulsions Plain amber medicine bottle Shake the bottle 4 weeks with CRC Enemas Amber fluted bottle with CRC For rectal use onlya 4 weeks Warm to body temperature before use Gargles and mouthwashes Amber fluted bottle with CRC Not to be takena 4 weeks Do not swallow in large amounts Inhalations Amber fluted bottle with CRC Not to be takena 4 weeks Shake the bottle Linctuses Plain amber medicine bottle 4 weeks with CRC Liniments and lotions Amber fluted bottle with CRC For external use only 4 weeks Shake the bottle Avoid broken skin Mixtures and suspensions Plain amber medicine bottle Shake the bottle 4 weeks with CRC Nasal drops Hexagonal amber fluted glass Not to be takena 4 weeks bottle with a rubber teat and dropper closure Ointments Amber glass jar For external use only 3 months Pastes Amber glass jar For external use only 3 months Pessaries Wrapped in foil and packed in an For vaginal use onlya 3 months amber glass jar Powders (individual) Wrapped in powder papers and Store in a dry place 3 months packed in a cardboard carton Dissolve or mix with water before taking See BNF for advisory labels recommended for active ingredient Suppositories Wrapped in foil and packed in an For rectal use onlya 3 months amber glass jar See BNF for advisory labels recommended for active ingredient BNF, British National Formulary; CRC, child-resistant closure. a See page 91 (General principles of labelling). paramount importance as it conveys essential infor- reminder of the key points that the patient needs to mation to the patient on the use of the preparation. know. Although the pharmacist or other healthcare prac- The functions of a label are to indicate clearly: titioner may counsel the patient when the medication is handed over, it is unlikely that the patient will be * the contents of the container able to remember all the information that they are * how and when the medicinal product should be given verbally. The label therefore acts as a permanent taken or used also legally required.g. The legislation distinguishes between Ensure the container is clean before packing the prod. labelling of a medicinal product for sale and the label- uct. Mrs. is the curved side and the front of a fluted bottle is Patients may feel embarrassed to ask for further the plain side. then clean the outside before affixing the label. with the date being reset automatically. but most labels used for to ensure that it can be read clearly. clarification on the meaning of complicated words * Cartons – The label should be placed on the large used on the label. inal products are contained in the Medicines Act 1968 and in amendments to that Act made by Statutory Cleanliness Instrument. label. side of the carton. the quantity dispensed. and if possible the title of the patient Make sure that the label is secure before dispensing the (Mr. If there is not enough room on a * Accurate – Ensure that the title is accurate. not crooked. ensuring that the contents of the In the UK detailed requirements for labelling of medic- label are visible when the top is placed on the jar. making reading none of the information. rather than reducing the size of the print or 2 All labels must state the name of the product trying to cram too much information onto one dispensed. the strength where appropriate. The information on the label should be: The words ‘Keep out of the reach of children’ are * Legible – Always check label print size and quality also legally required. it must be * any warnings or cautions that the patient needs to remembered that it is important not to confuse the be made aware of. If there is too dispensing purposes are already pre-printed with much information to place on one label.94 | Pharmaceutical forms and their preparation * how the product should be stored and for how * Concise – Although it is important that sufficient long information is placed on the label. all the information is visible. 1 All labels for dispensed medicines must have the name of the patient. Master. the single side of the carton for the entire label. Miss.) as this helps to product to the patient. as this risks spoiling the label with drips of the medicament. ling for a dispensed product. The front of an internal bottle understandable and use unambiguous terms. . The date sticking to product containers is dirt or grease on the and the name and address of the pharmacy are outside of the container. not Security just initials. * Ointment jars – The label should be placed on the Dispensed type labels side of the jar. when lesser requirements Never pour any liquids into a pre-labelled container apply. and label. ensuring that complete and accurate. * Adequate – Ensure that sufficient information is sure that the patient can open the container without destroying the label (e. be easily down the container. etc. patient by placing too much information on the label. If the label contains too much information. when labelling cartons) and given. ‘Keep placing the additional information on a secondary out of the reach and sight of children’. they may feel Positioning overwhelmed and this may result in the patient It is important to position the label with care. The main reason for labels not distinguish between family members. Appearance rather than assisting the patient. the questions How much? How often? When required for what? * Medicine bottles – The label should be on the * Intelligible – The wording of the information on front of a medicine bottle about a third of the way the label must be in plain English. This will normally automatically appear on most computer labelling Information systems. it instructions are accurate and the patient’s name is should be placed around the carton. preferably the full name. for example the term ‘when required’ leaves placing the label straight. consider these words or more commonly these days. Ms. ‘Discard after 31. However. In the UK. Ammonia and Containing: Ipecacuanha Mixture BP). the quantitative particulars are * Nasal drops – ‘Not to be taken’. other liquids or gels for external use. In the case of products for * Inhalations – ‘Not to be taken’. external use. However. of ‘For external use only’ to more closely reflect ‘The Ear Drops’. Sodium Bicarbonate 1968 defines products for external use as embro- Ear Drops BP or Sodium Chloride cations.10 by ‘a’) As with preparations intended for oral are: use. The Medicines Act 1968 (as etc. For example.e. for the following dosage forms.e. the a month and year after which the product should formula must be stated on the label). Lotion 4% would be labelled: Pharmacists should use their professional The Lotion judgement when deciding which auxiliary Containing: labels should be applied to different pharma- Sodium Chloride BP 4 g ceutical dosage forms.g. to be labelled with the full quantitative * Gargles and mouthwashes – ‘Not to be taken’. The Medicines Act title should be used (e. the term ‘For require slightly different labelling. for example ‘The Nose Drops’.10 gives guidance on the use of addi- preparations not intended for oral use tional auxiliary labels. etc. the positive one should be chosen Freshly boiled and cooled purified water (e. native labels (indicated in Table 5. label title may reflect the type of external alternative labels have been employed instead product. ‘The Mouthwash’. lotions. For not be used. 5. 3b Products for external use – Labels for Table 5. one with an accepted Similarly. 200 mL of Sodium Chloride BP Lotion formula that can be found in an official text). See Table be labelled ‘The Mixture’ or ‘The Solution’. Extemporaneous dispensing | 95 3a Products for internal use – The title of an Freshly boiled and cooled purified water extemporaneous preparation if it is an to 100 mL official product (i.10 for guidance. liquid antiseptics. These alter- Lotion’. unofficial products for external use need * Enemas – ‘For rectal use only’. expressed as the complete formula. to 200 mL for example a doctor’s own formula) it may 4 Labels must also include an expiry date. ‘The Enema’. a Freshly boiled and cooled purified water product made from an individual formula. a Sodium Chloride BP 5 Warning labels may also be required. ‘The the intended purpose of the product. If the external use only’ is used on any preparation product being made is official the official intended for external use. 100 mL Sodium Chloride BP * Suppositories – ‘For rectal use only’.g. As it is accepted practice . These may solution 4% with a dose of 10 mL bd could be pharmaceutical or pharmacological warnings be labelled as: (see labelling appendix in the British National The Solution Formulary).01. if there is a choice Each 10 mL dose contains: between two warning labels with equivalent Sodium Chloride BP 400 mg meanings. Therefore. in practice this can cause preparations intended for internal use this is confusion and an alternative format is to show expressed as the amount of ingredient per expiry as a single discard date: for example unit dose. ‘For rectal use only’ is preferable to ‘Do to 10 mL not swallow’ for suppositories). liniments. Mouthwash BP). 4% would be labelled: The title should be as quoted in the official The Lotion text (for example. Unofficial products must state the full amended) requires medicinal products to specify quantitative particulars on the label (i. If the product is an unofficial one the traditionally. Sodium Chloride BP 8 g If it is an unofficial product (that is.10’. Generally. * Pessaries – ‘For vaginal use only’. particulars. * robust enough to protect the contents against 7 Where possible adjacent numbers should be crushing during handling and transport separated by the formulation name. as some patient groups b Use ‘Give’ as a dosage instruction on (e. access to medication by children. that is not intended for the oral route of Consideration should be given to the patient when administration. for example ‘Take two’ The function of a container for a medicinal product is to (not ‘Two to be taken’). e. This is because a 5 mL spoon is the normal unit provided to the patient to Although different pharmaceutical preparations measure their dose from the dispensed bottle. to be used’). For example. ‘two’ not ‘2’). All dispensed medicinal products will need to be dis- 6 All directions on labels should use active rather pensed to the patient in a suitable product container. can lead to non-compliance or reduced compliance. be inert 8 Liquid preparations for internal use usually * sufficiently transparent to allow for inspection of have their dose expressed as a certain number the contents in the case of liquid preparations of 5 mL doses. especially if the formulation. All other Medicine bottles dosage instructions should use words in Plain amber medicine bottles preference to numerals. * convenient to use in order to promote good ‘Take two three times a day’ could easily be patient compliance (i. Tablet bottles Paediatric prescriptions may ask for a 2. safety and stability of its contents. Traditional amber verbal explanation of the label. Plain amber medicine bottles can be used to package d Always be prepared to give the patient a all internal liquid preparations. the elderly and arthritic patients) may not be able products for children. these Pharmaceutical packaging will be the terms used in each of the product chapters. They are used for solid. therefore ideally take their medication at the correct times) the wording on this label would include the * easy to open and close. all tablet bottles should be that the item can be identified and the patient fitted with child-resistant closures.10). Simple not child-proof. medicine bottles used in the UK have two different . ‘Take two tablets three times a medication is for an elderly or arthritic patient day’. if a prescription called for the on the product type. so the materials of construction should numeral (i. tablets and capsules) (Figure 5.g.g. pharmaceutical packaging can dosage instruction 10 mL tds this would be largely be grouped into a few main types. They are 2.e. encourage the patient to misinterpreted by the patient. preparation is for a child and would be given to single-dose preparations that are intended for oral use the patient by the parent or guardian. as a responsible adult to open the container to access their medication. There are a number of a Never use the word ‘Take’ on a preparation different types of child-resistant closures on the market.96 | Pharmaceutical forms and their preparation in the UK to use the terms outlined above. etc. 9 Remember the label on a medicine is included so In normal circumstances. In this case the label would read ‘Give a are usually made of either glass or plastic.5 mL dose using the oral syringe provided’. will be packaged in different containers depending Therefore. usually coloured amber to reduce the likelihood of the Note here the use of the word ‘Give’ as the contents reacting with light. ‘Use one’ (not ‘One maintain the quality. using child-resistant closures. (i. if required. these closures reduce the possibility of language should be used. The frequency and quantity of individual * constructed of materials that do not react with the doses is always expressed as a word rather than a medicine. c Only use numerals when quoting the number of millilitres to be given or taken. than passive verbs. expressed as ‘Take two 5 mL spoonfuls three times a day’.e. This should administer them. Although they are instructed as to the directions for use.5 mL Tablet bottles come in a variety of shapes and sizes and dose.e. ‘Insert one’ (not ‘One to be The ideal container should be: inserted’). ment (Medicines Act 1968) in the UK that fluted bot- Plain amber medicine bottles come in a variety of tles be used with specific types of pharmaceutical sizes. For this when in use. By placing the label on the curved side. one curved and one flat. although other sizes Fluted amber medicine bottles may be available (Figure 5. There is a legal require- side of the bottle during pouring of a dose. The capacity of each bottle is traditionally preparation: embrocations. The ridges or grooves up with the curved side of the bottle facing the inside of are intended to be both a visual and tactile warning to the palm.10 Selection of tablet bottles. this side is curved and contains usually placed on the curved side of the bottle as the a number of ridges or grooves running from the top of natural action by the patient will be to pick the bottle the bottle down to the bottom. 200 mL. antiseptics. liquid marked on the bottom of the container in millilitres. these types of container are often referred to damaged by any dribbles of liquid running down the as ‘external medicine bottles’.11).11 Selection of plain amber medicine bottles. In the UK. 150 mL. other liquids or gels for external use. the label is following sizes: 50 mL. Fluted (or ribbed) amber medicine bottles are similar As with tablet bottles. Extemporaneous dispensing | 97 Figure 5. Figure 5. . lotions. child-resistant closures bottom of the container in millilitres. this the patient or carer that the contents of the bottle are will mean the label is on the upper side of the bottle not to be administered via the oral route. capacity of each bottle is traditionally marked on the As with tablet bottles. In the UK. child-resistant closures to the plain amber medicine bottles but instead of should be used whenever possible. 100 mL. placed on the smooth curved side of the bottle and the 300 mL and 500 mL (Figure 5. The label or labels are having a flat plain side. This will prevent the label becoming reason. sides. amber medicine bottles typically come in the following sizes: 50 mL. liniments. 100 mL and 200 mL. fluted should be used whenever possible.12). plain amber medicine bottles come in the As with plain amber medicine bottles. 3 Remove the water from the bottle and drain the bottle. Additional 1 Measure a volume of water equal to that of the care must be exercised in the storage of pharmaceutical product being prepared. depend- a conical measure (see Chapter 4). 5 Add any liquid ingredients and make the mixture up to volume using the vehicle.13 Selection of cartons. Calibrated containers for liquid preparations Cartons Liquid preparations are normally made up to volume in Cardboard cartons come in a variety of sizes. Although it is good dispensing practice to very dense suspension and transference may cause pro. There are occasions ing on the manufacturer. in some cases this is not possible. Figure 5. for labelling the product in question (for example the To tare a container: labelling of very small eye dropper bottles). blems. . products that may be of a shape that is not suitable for For example. because of the box. Placing the primary cult and time consuming to transfer in its entirety container into a labelled carton is the next best method because of the viscosity of the finished product.12 Selection of fluted amber medicine bottles. This must be measured products in cardboard cartons as they do not come accurately using a conical measure. this method can only be used where water is one of the ingredients of the mixture.13). 6 Remove the meniscus marker before dispensing the preparation to the patient. A tared in shape and the label is placed on the larger side of the bottle is normally only employed when. with child-resistant closures (Figure 5. 4 Transfer the prepared mixture into the calibrated bottle.98 | Pharmaceutical forms and their preparation Figure 5. similarly. powder papers and other pharmaceutical the measure to the container would be unacceptable. as putting medi- cines into a wet bottle is considered to be bad practice. a thick emulsion will also prove diffi. 2 Pour the water into the container and mark the meniscus using a small adhesive label. Rinse the measure or mortar used in the preparation of the product with more vehicle and add this to the bottle. label the primary container of a medicinal product. They are used to package blister strips of tablets viscosity of the final product. They tend to be rectangular where a tared or calibrated bottle may be used. Please note that unless the bottle is thoroughly dried after taring. the transference loss from or capsules. Kaolin Mixture BP (see Chapter 16) is a labelling. As Ointment jars come in a variety of different sizes and with cartons.14). the storage of ointment jars as they do not come with Amber ointment jars are used for preparations that are child-resistant closures (Figure 5.14 Selection of ointment jars. Extemporaneous dispensing | 99 Figure 5. . sensitive to light. additional care must be exercised in can be made of either colourless glass or amber glass. They are used to package ointments. Ointment jars creams and individually wrapped suppositories. . and hence the speed of preparation of an ad hoc for. as it is non-toxic.6 Solutions Introduction and overview 101 Gargles and mouthwashes 105 General principles of solution preparation 103 Enemas and douches 105 Solubility 103 External solutions 105 Stability 103 Lotions 105 General method 103 Liniments 105 Oral solutions 104 Applications 105 Elixirs 104 Collodions 106 Linctuses 105 Worked examples 106 Syrups 105 Summary of essential principles relating to solutions 112 Mixtures 105 Packaging 112 Draughts 105 Discard dates 112 Spirits 105 Labelling 113 Paediatric drops 105 Introduction and overview Essentially a solution is a homogeneous liquid preparation that contains one or more dissolved med- Solutions are one of the oldest dosage forms used in the icaments. Owing to the simplicity mulation types (e. relatively cheap. Problems may be encountered psychiatric patients). tasteless. ing water mixed with a variety of other solvents. may be obtained without any need to shake the for- the compounding of solutions retains an important mulation.g. geriatric. where compliance needs to be where active drugs are not particularly water soluble checked on administration (for example in prisons or or suffer from hydrolysis in aqueous solution. This is an advantage over some other for- place in therapeutics today. and many drugs (for example paediatric. by definition. indi. active ingredients are treatment of patients and afford rapid and high dissolved within the vehicle. water is chosen as the vehicle in which mulation. uniform doses by volume absorption of soluble medicinal products. non- who have difficulty in swallowing solid dosage forms irritant. they are of particular use for individuals medicaments are dissolved. intensive care and are water soluble. In these psychiatric pharmacy) and in cases where precise. In general. suspensions. cases it is often possible to formulate a vehicle contain- vidualised dosages are required. see Chapter 7). . Therefore. Since. solutions required.1. In (for example the free alkaloid or its salt) in order these situations. It is possible to attempt The advantages of solutions as pharmaceutical pro. Unlike the volume administered may result in large some liquid preparations (e. dosage forms are summarised in Box 6. Although the dose can be solution to be taken is all that is required. it must be products are that: borne in mind that a measuring device will need to be supplied to the patient in order for them to be * Drug stability is often reduced in solution by able to measure an accurate dose (this will have solvolysis. For device. this reason. administered is very small. Although are defined as ‘Oral Liquids containing one or more liquid dosage forms may be ideal for small active ingredients dissolved in a suitable vehicle’. The solubility of a there is no need to shake the container to ensure a drug needs to be taken into consideration when uniform dose is measured. breakages. traditionally. the drug dosage forms is that they are always much larger needs to dissolve before absorption into the body and more bulky than their comparable solid can take place. it is common for solutions to attract a shorter expiry date than equivalent solid dosage The advantages and disadvantages of solutions as forms. These are obviously prone within the solution will be present in a certain to breakage which can be hazardous and cause the concentration per unit volume. This makes them heavier and more the dissolution phase of the absorption process can difficult to transport. hydrolysis or oxidation. pharmaceutical liquids are * Flexible dosing is possible. patient accuracy in measuring a dose is of administration is often considered. topical (for use on the skin) preparing a liquid preparation.g. measure an accurate dose can vary considerably Parenteral preparations (injections). Some volume produced is not excessive. providing quicker absorption. By providing the drug in a solution. If alterations to the loss of the preparation. The disadvantages of solutions as pharmaceutical Although not a major disadvantage. preparing a solution to ensure that the final * They facilitate swallowing in difficult cases. titrated without the need to produce additional * They may be designed for any route of absorption. preparations (see point 2 from the advantages Although when discussing solutions the oral route above). The stability cost implications). a simple alteration to the quantity of on administration. difficult to transport and prone to * The drug is immediately available for absorption. A major disadvantage of all liquid When solid dosage forms are taken orally. to mask any unpleasant tastes by the addition of a ducts are that: flavouring. but this will not always be successful. This is especially preparations and ophthalmic preparations can important when the volume of liquid to be all be solutions. Coupled with this is the fact be bypassed. The active ingredient packed in glass bottles. formulation.g. suspensions).102 | Pharmaceutical forms and their preparation In the British Pharmacopoeia (BP). . formulated into a solution. where small changes in * There is no need to shake the container. as the increases or decreases in dose. It is accepted that patients’ abilities to can be administered via a number of other routes. enemas for and this needs to be taken into consideration when rectal use. and in addition the patient will of the active ingredient needs to be taken into need counselling on the use of the measuring consideration when formulating a solution. many drugs taste unpleasant when and disadvantages compared with other dosage forms. * A measuring device is needed for administration. oral solutions * It is difficult to mask unpleasant tastes. infants or the elderly). that. * They are bulky. take a liquid dosage form. In some cases it patients may find it hard to swallow traditional may be necessary to alter the vehicle or drug form solid dosage forms (e. quantity of active ingredient to be administered * Technical accuracy is needed to measure the dose are required. it may be easier for the patient to to be able to formulate a convenient preparation. active ingredient is dissolved within the vehicle * Some drugs are poorly soluble. children who are unable to swallow solid dosage Solutions provide a number of distinct advantages forms. page 70). * How long will dissolution take? 6 Identify the soluble solids and calculate the * Will the drug(s) remain in solution and for how quantity of vehicle required to fully dissolve the long? solids.). of solutions as it is relatively easy to transfer the entire final contents of the conical measure.g. Solutions | 103 * What is the pH of solvent required for Box 6. as far as is practically possible. tinctures. Remember. During compounding. as described in Chapter 4.g. preparation photosensitivity. by the nature of preparation of a solution: their formulation (e. ophthalmic. and the microbiological stability Historically. the solid(s) will need to Flexible dosing Difficult to mask go through a dissolution phase.g. . etc. component of the solvent system? page 91). aromatic waters. Solubility Also. * What quantity of drug will dissolve? 5 Weigh all solids. nasal or parenteral). as will the chemical stability and time period. (official). topi- The following general method should be used in the cal. Measuring device needed for administration Some drugs poorly soluble Stability In addition to the solubility of the drug element(s) of the formulation. prescription (unofficial) or from an official text spirits. or to be categorised by a traditional name that relates to the 1 Write out the formula either from the solvent system used and/or their intended function (e. * Will the drug(s) dissolve in the solvent or a 4 Prepare a suitable label (see Chapter 5. order to fulfil a wide variety of pharmaceutical func- tions. the product will be assembled in the final measure. Although the precise characteristics of different 2 Calculate the quantities required for each types of solution may vary. thus The following points relating to the solubility of the reducing any transference losses.g. The two required final volume. It is therefore common to find solutions classified General method according to their intended use (e. If more than one solid is to be dissolved. simple or complex). other considerations regarding the physical stability of the preparation will need to be General principles of solution taken into consideration (e. drug element(s) of the formulation need to be taken 3 Complete all sections of the product worksheet into consideration: (see Chapter 5. temperature variation. May be designed for any unpleasant tastes it is worth remembering that dissolution rates gener- route of administration Bulky. syrups and elixirs).1 Advantages and disadvantages of dissolution? solutions as dosage forms Answers to many of the above questions will Advantages Disadvantages require the compounder to perform a solubility calcu- Drug available immediately Drug stability often lation. a range of solutions have been developed in and need for a preservative. difficult to transport ally increase with: No need to shake container and prone to container Facilitates swallowing in breakages * smaller particle sizes difficult cases Technical accuracy needed * effective stirring to measure dose on * lower viscosities administration * increased temperature. the essential principles ingredient in the formula to produce the governing their preparation remain similar. oral internal. for absorption reduced in solution When preparing a solution. it is not usual key characteristics that need to be considered when to calculate for an overage of product in the case compounding solutions are solubility and stability. high concentration planes within glass beaker. * Aqueous solutions should be added to alcoholic 12 Add any remaining liquid ingredients to the solutions with stirring to maintain the alcohol conical measure and stir. automatic stirring devices the vehicle used in elixirs. solutions should be flavouring agent.g. stirred gently and uniformly to avoid air In general. rod. there are important differences between the different solution types. label and dispense to the patient. the action of the stirring portion of sugar or other sweetening agent. * Completely dissolve salts in a small amount of 10 When all the solid(s) have dissolved. Oral solutions See Solutions video for a demonstration of the preparation of a solution. in order of uniform product and can be timesaving. remember to remove them take place in a glass (or occasionally plastic) before adjusting to final volume. solution: 9 Transfer the solid to the beaker and stir to aid dissolution. concentration as high as possible – the reverse may 13 Make up to final volume with remaining vehicle. organic components should 11 Rinse out the beaker in which the solution was be dissolved in alcoholic solvents and water- made with a portion of the vehicle and transfer soluble components dissolved in aqueous solvents. for a number of reasons. Remember that * It is best to stir continuously when combining the solubility of the soluble solids will be ingredients into a solution (either liquid or solid dependent on the vehicle used.104 | Pharmaceutical forms and their preparation they are dissolved one by one. 14 Transfer to a suitable container. the fluid body. * In complex solutions. First. Second. If stirring solubility (i. dissolution will magnetic stirrers). 4. In almost all cases. completer transfer of the powders. By stirring continually during 7 Transfer the appropriate amount of vehicle to a incorporation. to hold the final solution. which may result in foaming of the or propylene glycol) form a significant proportion of solution. the rinsings to the conical measure. If a mortar and pestle have been * To aid dissolution. included to rod may scratch the inside of the glass. owing to the shape of the conical Elixirs measure. The stir the solid around with the stirring rod. or alternatively solubilising may be useful in assisting the production of a agents are included. and use the glass pestle to reduce particle size to Further considerations during the preparation of a aid dissolution. . * Dissolution will normally take place in a glass beaker.e. This section describes the different types of pharma- ceutical solution that are used orally. are usually formulated with a fruit syrup as a base * During the dissolution phase. Paediatric elixirs altering the internal volume of the measure. permanently mask offensive or nauseating tastes. which formulation is clear and generally contains a high pro- aids dissolution. which might increase the 8 If necessary. transfer the water prior to the addition of other solvent solution to the conical measure that will be used elements. transfer the solid to a glass mortar likelihood of incompatibilities. Although all are prepared using the same general techniques high- Key points from the method lighted above. If available. will be avoided. the least soluble first. result in separation of any dissolved components. non-aqueous solvents (alcohol. not a conical measure. beaker. see Chapter devices are used to assist dissolution (e. page 62). glycerin entrapment. not a conical measure. high-viscosity liquid used to reduce particle size. ingredients). any solid added will tend to ‘cake’ at the An elixir is a liquid oral preparation that usually con- bottom of the measure and hamper any attempt to tains either potent or unpleasant-tasting drugs. ensure that the components should be added to those of lower mortar is rinsed with a little vehicle to ensure viscosity. g. a linctus tainer used will be easily distinguishable from those is intended to be sipped slowly and allowed to trickle containing preparations intended to be swallowed. such as the vagina or one or more sugar components. linctuses are formulated as viscous solutions which Enemas and douches contain sugars. problems of flammability are addressed by suitable labelling. chiefly sucrose. page 29. where the vehicle for the medication is alcohol based. These liquid preparations are often formulated as solu- Syrups tions (though they may be presented as an emulsion or suspension) and are intended for instillation into the A syrup is a concentrated. allowing for rapid Spirits are solutions containing one or more active drying of the hair and thus making the product more medicaments dissolved in either absolute or dilute acceptable to the patient (e. in a volume Lotions which is larger than generally utilised in traditional Lotions are solutions. Gargles and mouthwashes Applications Gargles and mouthwashes are aqueous solutions that Applications are solutions. but may also be suspensions or mixture formulations. A liniment is a liquid preparation intended to be diatric patients. In some cases Spirits lotions are applied to the scalp. Simple liquid preparations intended for oral use con- taining dissolved medicaments may be described as External solutions oral solutions or mixtures. The volumes of these preparations described in more detail in Chapter 2. dressing or covering material. BPC). As such. instructions are included on the label and that the con- principally in the treatment of cough. intended to be applied with- mouth (mouthwashes) and are generally formulated in out friction to the skin and to be used without any a concentrated form. must be administered with a calibrated dropper. down the throat in an undiluted form. rubefacient or generally stimulating is designed to have very small dose volumes which effects. The formulation obtain analgesic. a number of different preparation types Draughts have been developed for external use. When the larger volumes are used it is important that the liquid is Mixtures warmed to body temperature before administration. In these cases. Solutions | 105 Linctuses These preparations must be diluted before use and A linctus is a liquid oral preparation that is chiefly used care should be taken to ensure that appropriate for a demulcent. Consequently. Paediatric drops These are an oral liquid formulation of potent drugs Liniments usually in solution. though they may be useful in other rubbed with friction and massaged onto the skin to patients with swallowing difficulties. owing to the versatility of the solution. Salicylic Acid Lotion 2% ethanol. expectorant or sedative purpose. They are usually solutions of oils. Liniments should not be used on broken skin. may vary from 5 mL to much larger volumes. emulsions. viscous solution containing rectum (enema) or other orifice. As with internal solutions. intended for administration to pae. . and is nasal cavity (douche). without friction on a carrier fabric such as lint and covered with a waterproof dressing. that are intended to be applied to the skin plied in a 50 mL unit dose container. though they may also be are intended for treatment of the throat (gargles) and suspensions or emulsions. alcohols or soaps. A draught is an older term used to describe a liquid preparation formulated as a single dose. although the term ‘mixture’ may also be applied to a suspension. Each draught was usually sup. but may be formulated as emulsions. page 32): Concentrated Chloroform 5 mL Water BPC 1959 Potable water to 100 mL Method: 1 Using the master formula from the British Pharmacopoeia for 1000 mL of final product. page 736): 1000 mL 100 mL 50 mL 150 mL Concentrated Compound Gentian Infusion BP 100 mL 10 mL 5 mL 15 mL Sodium Bicarbonate BP 50 g 5g 2. the quantities in the master formula are first divided by 10 to give a product with a final volume of 100 mL. Point of clarity – Step 1 Rather than attempt this conversion in one stage. . in contact with the skin for an extended period.106 | Pharmaceutical forms and their preparation Collodions be used to seal minor injuries or retain a dissolved drug These are principally solutions of pyroxylin in a vehi. In the example given here. Do not use after (2 weeks) Name of patient Date of dispensing Product formula (British Pharmacopoeia 1988. Worked examples Example 6. calculate the quantity of ingredients required to produce the final volume needed (150 mL).5 g 7. When dry. cle of ether and alcohol that are intended to be painted Collodions are highly volatile and highly flamma- onto the skin and left to dry. it may be simpler to take the calculation through a number of stages. the collodion ble and care should be taken to label any preparation leaves a flexible film of cellulose on the skin which may appropriately. the compounder is less likely to make a calculation error. These quantities are then halved to give a product with a final volume of 50 mL.5 g Double Strength Chloroform Water BP 500 mL 50 mL 25 mL 75 mL Potable water to to to to 1000 mL 100 mL 50 mL 150 mL Interim formula for Double Strength Chloroform Water BP (see Chapter 2. The quantities in the 100 mL product and 50 mL product are then added together to give the quantities of ingredients in a product with a final volume of 150 mL. By using this method.1 Preparation of 150 mL of Alkaline Gentian Mixture BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Gentian Alkaline Mixture BP 150 mL Product directions. Point of clarity – Step 4 As discussed above.5 g of Sodium Bicarbonate BP in this example. Solutions | 107 Example 6. When choosing the amount of vehicle to use for dissolution.e. sufficient to satisfy the formula requirements but also enabling simple. e Visually check that no undissolved chloroform remains at the bottom of the measure. 3 Weigh 7.5 mL). it is important to consider the total amount of each liquid ingredient in the preparation to ensure that only the correct amounts are added or the final product does not go over volume.5 mL of vehicle would be required to dissolve the 7. See Solutions video for a demonstration of the preparation of Double Strength Chloroform Water BP. all the Double Strength Chloroform Water BP is used (75 mL) along with enough potable water to reach the desired volume (approximately 15 mL). 7.5 mL (7. In this case.5 g Sodium Bicarbonate BP). For ease of compounding choose a convenient volume of vehicle. In this example. To compound Double Strength Chloroform Water BP: a In this case. measure 5 mL of Concentrated Chloroform water BPC 1959 accurately using a 5 mL conical measure.5 g Sodium Bicarbonate BP on a Class II or electronic balance. in this example 90 mL of vehicle is required to dissolve the Sodium Bicarbonate BP. accurate measurement of the concentrated component. say 90 mL. sufficient water to enable dissolution of the concentrated chloroform component without reaching the final volume of the product). Noting that sodium bicarbonate is soluble 1 in 11 with water. b Add approximately 90 mL of potable water to a 100 mL conical measure (i. d Stir gently and then accurately make up to volume with potable water. The final volume of Gentian Alkaline Mixture BP required (150 mL) will contain 7. a minimum of 11 mL of water would be required to dissolve 1 g of sodium bicarbonate. To this add approximately 15 mL potable water in order to produce 90 mL of vehicle which should be poured into a beaker (in order to produce sufficient volume to dissolve the 7. 75 mL of Double Strength Chloroform Water BP is required and so it would be sensible to prepare 100 mL. it would be incorrect to dissolve the Sodium Bicarbonate BP in 90 mL of Double Strength Chloroform Water BP as the final volume of the preparation only contains 75 mL.5 g is soluble in 82. in which to initially dissolve the solute. c Add the measured Concentrated Chloroform Water BPC 1959 to the water in the conical measure. It is important to consider the total amount of each liquid ingredient in the product to ensure that only the correct amounts are added.5 g of Sodium Bicarbonate BP. Therefore a minimum of 82. As 1 g of sodium bicarbonate is soluble in 11 mL. . To prepare 100 mL Double Strength Chloroform Water BP.1 Continued 2 Calculate the composition of a convenient quantity of Double Strength Chloroform Water BP. 4 Accurately measure 75 mL Double Strength Chloroform Water BP using a 100 mL measure.5 11 ¼ 82. Do not use after (4 weeks) Name of patient Date of dispensing Product formula (British Pharmacopoeia 1988. As with Example 6.5 mL aqueous vehicle. 3 Measure approximately 15 mL potable water and transfer to a beaker. page 720): 1000 mL 500 mL 50 mL Ammonium Chloride BP 100 g 50 g 5g Aromatic Ammonia Solution BP 50 mL 25 mL 2. the 5 g required for this product would only dissolve in a minimum initial volume of 13.108 | Pharmaceutical forms and their preparation Example 6. 2 Weigh 5 g Ammonium Chloride BP accurately on a Class II or electronic balance. 8 Rinse the beaker with potable water. adding the rinsings to the Sodium Bicarbonate BP solution.5 g) should be added to the vehicle.7 parts of water. 11 Transfer the solution to a 150 mL amber flat medicine bottle with a child-resistant closure and label. See Solutions video for a demonstration of the preparation of a solution. 9 Accurately measure 15 mL of Concentrated Compound Gentian Infusion BP in an appropriately sized conical measure and add to the Sodium Bicarbonate BP solution in the 250 mL measure. Rinse out the small conical measure with potable water and add the rinsings to the mixture.5 mL Liquorice Liquid Extract BP 100 mL 50 mL 5 mL Potable water to 1000 mL to 500 mL to 50 mL Method: 1 Calculate the quantity of ingredients required to produce the final volume needed.2 Preparation of 50 mL Ammonium Chloride Mixture BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Ammonium Chloride Mixture BP 50 mL Product directions. this calculation is best attempted in stages. .1. thus following the principle of adding solutes to solvents. 6 Stir to aid dissolution. Therefore we should choose a convenient volume of vehicle to dissolve the solute. say 15 mL. 10 Make up to volume (150 mL) accurately with potable water and stir. 7 Transfer the solution to a 250 mL conical measure. Example 6.1 Continued 5 The Sodium Bicarbonate BP (7. As ammonium chloride is soluble 1 part in 2. 75 mL Double Strength Chloroform Water BP 500 mL 50 mL 25 mL 75 mL Potable water to 1000 mL to 100 mL to 50 mL to 150 mL Interim formula for Double Strength Chloroform Water BP (see Chapter 2.25 mL 3. . Dilute with an equal volume of water before use. calculate the quantity of ingredients required to produce the final volume needed (150 mL). 8 Make up to the final volume of 50 mL with potable water and stir.25 g Concentrated Peppermint Emulsion BP 25 mL 2. to the 50 mL measure containing ammonium chloride solution. 7 Measure 2. with rinsings. See Solutions video for a demonstration of the preparation of a solution. Solutions | 109 Example 6. page 703): 1000 mL 100 mL 50 mL 150 mL Sodium Bicarbonate BP 10 g 1g 500 mg 1.5 g Sodium Chloride BP 15 g 1.2 Continued 4 Add the Ammonium Chloride BP to the water in the beaker and stir until dissolved.3 Preparation of 150 mL of Sodium Chloride Compound Mouthwash BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Sodium Chloride Compound Mouthwash BP 150 mL Product directions.5 g 750 mg 2. 6 Measure 5 mL Liquorice Liquid Extract BP accurately in a 5 mL conical measure and add. page 32): Concentrated Chloroform Water BPC 1959 5 mL Potable water to 100 mL Method: 1 Using the master formula from the British Pharmacopoeia for 1000 mL of final product. 5 Transfer to a 50 mL conical measure with rinsings.5 mL Aromatic Ammonia Solution BP accurately in a syringe and transfer to the 50 mL measure containing the composite solution. Do not swallow in large amounts Not to be Taken Do not use after (4 weeks) Name of patient Date of dispensing Product formula (British Pharmacopoeia 1988.5 mL 1. 9 Pack into a 50 mL amber flat medicine bottle and label. Example 6. sufficient water to enable dissolution of the concentrated chloroform component without reaching the final volume of the product). Noting that sodium bicarbonate is soluble 1 in 11 with water.75 mL of Concentrated Peppermint Emulsion BP using a 5 mL and a 1 mL syringe. As 1 g of sodium chloride is soluble in 2. 7 When the Sodium Bicarbonate BP has dissolved. b Add approximately 90 mL of potable water to a 100 mL conical measure (i.5 g Sodium Bicarbonate BP on a Class II or electronic balance.25 g of Sodium Chloride BP. 75 mL of Double Strength Chloroform Water BP is required and so it would be sensible to prepare 100 mL.3 mL (2.8 ¼ 6. 10 Measure 3. Therefore a minimum of 2.5 g of sodium bicarbonate and a minimum of 6.110 | Pharmaceutical forms and their preparation Example 6. When choosing the amount of vehicle to use for dissolution.25 2. The sodium chloride is soluble 1 in 2. 5 Measure 75 mL of Double Strength Chloroform Water BP in a 100 mL conical measure.25 g of sodium chloride in this example. For ease of compounding choose a convenient volume of vehicle. 8 Transfer the solution from the beaker to a 250 mL conical measure.5 mL of vehicle would be required to dissolve the 1.5 g is soluble in 16. d Stir gently and then accurately make up to volume with potable water.5 mL (1. The final volume of Sodium Chloride Compound Mouthwash BP required (150 mL) will contain 1.5 g of Sodium Bicarbonate BP. 13 Transfer to a 200 mL amber fluted medicine bottle and label. Method of compounding for Double Strength Chloroform Water BP: a In this case.8 mL of water would be required to dissolve 1 g of sodium chloride. e Visually check that no undissolved chloroform remains at the bottom of the measure. The final volume of Sodium Chloride Compound Mouthwash BP required (150 mL) will contain 2. See Solutions video for a demonstration of the preparation of Double Strength Chloroform Water BP. See Solutions video for a demonstration of the preparation of a solution. measure 5 mL of Concentrated Chloroform water BPC 1959 accurately using a 5 mL conical measure. in which to initially dissolve the solute. add the Sodium Bicarbonate BP and stir to aid dissolution. 11 Add the Concentrated Peppermint Emulsion BP to the conical measure. . c Add the measured Concentrated Chloroform Water BPC 1959 to the water in the conical measure.5 mL). 9 Rinse out the beaker with some Double Strength Chloroform Water BP and add the rinsings to the conical measure.8 with water.25 g Sodium Chloride BP on a Class II or electronic balance.8 mL. As 1 g of sodium bicarbonate is soluble in 11 mL. a minimum of 11 mL of water would be required to dissolve 1 g of sodium bicarbonate. 3 Weigh 2. 1.3 Continued 2 Calculate the composition of a convenient quantity of Double Strength Chloroform Water BP. Therefore a minimum of 16.3 mL). say 30 mL. 4 Weigh 1. it is important to consider the total amount of each liquid ingredient in the preparation to ensure that only the correct amounts are added or the final product does not go over volume. add the Sodium Chloride BP and stir to aid dissolution.3 mL of vehicle would be required to dissolve the 2. To prepare 100 mL Double Strength Chloroform Water BP.25 g is soluble in 6. accurate measurement of the concentrated component. 2. 12 Make up to volume with the remaining Double Strength Chloroform Water BP and potable water.e. sufficient to satisfy the formula requirements but also enabling simple. 6 Transfer approximately 30 mL of Double Strength Chloroform Water BP to a beaker.5 11 ¼ 16. By using this method. To prevent this add approximately 20 mL of freshly boiled and cooled purified water to a glass mortar (Potassium Permanganate BP stains and so a porcelain mortar would not be suitable) and grind under water. 1 Weigh 300 mg Potassium Permanganate BP on a Class II or electronic balance.2% Freshly boiled and cooled purified water to 100% Name of patient Date of dispensing Product formula: 100 mL 50 mL 150 mL Potassium Permanganate BP 200 mg 100 mg 300 mg Freshly boiled and cooled purified water to 100 mL to 50 mL to 150 mL Point of clarity – product formula Rather than attempt the above conversion in one stage. The quantities in the 100 mL product and 50 mL product are then added together to give the quantities of ingredients in a product with a final volume of 150 mL. hair and fabric Do not use after (2 weeks) For External Use Only This solution contains: Potassium Permanganate BP 0. there are 200 mg of Potassium Permanganate BP in every 100 mL of solution. 2 Transfer to a glass mortar as the Potassium Permanganate BP is crystalline and for ease of dissolution needs to be ground into a powder.2% w/v 150 mL Product directions. Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Potassium Permanganate Solution 0. the compounder is less likely to make a calculation error. Point of clarity – Step 2 Potassium Permanganate BP is an oxidising substance therefore there is risk of explosion.2 g in 100 mL. In the example given above.4 Preparation of a magistral formulation (150 mL of Potassium Permanganate Solution 0. Freshly boiled and cooled purified water is used as the vehicle as no other preservative is included and the preparation is intended for application to an open wound. it may be simpler to take the calculation through a number of stages.2% w/v) from a doctor's prescription Given that 0. Method: Note that Potassium Permanganate is soluble in cold water and freely soluble in boiling water. Solutions | 111 Example 6. . the quantities in the master formula are first divided by 2 to give a product with a final volume of 50 mL.2% w/v is equal to 0. Caution: Stains skin. consideration should be on extemporaneously compounded solutions. and microbiological reasons. 6 Transfer the solution to a 150 mL amber fluted medicine bottle with a child-resistant closure and label. Because of the lack of complete control of conditions When selecting packaging for extemporane- and inability to perform retrospective stability tests ously prepared solutions. Liquid preparations that are intended for the oral For official preparations. shorter shelf-lives must be attributed. The exact impact of such processes on a compounded solution will depend Packaging largely upon the storage conditions. Summary of essential principles both sight and touch. this section tainer that is too large for the volume of preparation to contains: be dispensed for both cost and appearance issues (Table 6.4 Continued 3 Transfer the solution to a 250 mL conical measure. See Solutions video for a demonstration of the preparation of a solution. by for use. chemical (hydrolysis) pharmaceutical solutions. Obviously it is important not to use a con- extemporaneous preparation of solutions.112 | Pharmaceutical forms and their preparation Example 6. the British Pharma- route should be packed in plain (smooth) amber copoeia employs two definitions that are useful when bottles. . * further notes on the packaging of extemporaneously prepared solutions * specific points relevant to the expiry of Discard dates extemporaneously prepared solutions Extemporaneously compounded solutions are often * additional key points related to the labelling of relatively unstable for physical. A brief overview because of strictly controlled manufacturing environ- of the main considerations for the packaging of solu- ments supported by rigorous quality assurance testing. tions will be given here. Commercially available The packaging of extemporaneous preparations has manufactured products generally have long shelf-lives been covered in Chapter 5 (page 96).e. much given to the route or method of administration. amber bottles with vertical ridges or been compounded less than 24 hours prior to issue grooves).g. External preparations and preparations extemporaneously compounding solutions: that are not intended to be taken internally (e. of preparations that are not to be taken via the oral route. 4 Rinse the mortar with freshly boiled and cooled purified water and add the rinsings to the conical measure. 5 Make up to volume with freshly boiled and cooled purified water. This will enable simple identification. To assist compounders in understanding the dispensed. mouthwashes) should be packaged in fluted amber * ‘Freshly Prepared’ refers to a preparation that has bottles (i. relating to solutions Pharmaceutical bottles come in a variety of differ- This section recaps the main principles relating to ent sizes and it is important to choose a suitably sized solutions that have been covered in other sections of container to match the volume of preparation to be the book.1). the formulation and its intended purpose. Draughts 200 mL. A four-week expiry should be applied to oral solutions that require to be Recently Prepared. the following points need to be taken into consideration: compounder must take a number of considerations into account. An ferred method of indicating shelf-life on the label of overview of the main considerations for the labelling extemporaneously compounded products is to apply of solutions will be given here. Solutions | 113 Table 6. the labelling of extemporaneous preparations. Further guidance on expiry dates for pharma- In practical terms it is suggested that an expiry date ceutical preparations can be found in Chapter 5 of two weeks is applied to oral solutions that need to be (page 92).1 Summary of packaging for pharmaceutical solutions Typical sizes Pharmaceutical product examples include Oral liquids Amber flat medical bottle 50 mL. 200 mL Applications Collodions Enemas and douches Gargles and mouthwashes Liniments Lotions Amber fluted medical bottle with dropper top 10 mL Ear drops Nose drops * ‘Recently Prepared’ should be applied to * a solution where there are no stability data compounded items that are likely to deteriorate if available stored for a period greater than four weeks when * a new solution or ad hoc preparation. 100 mL. As a general rule. 500 mL Elixirs Linctuses Mixtures Spirits Syrups Amber round medical bottle with dropper top 10 mL Paediatric drops External liquids Amber fluted medical bottle 50 mL. 150 mL. the When dealing with unofficial preparations. the term ‘Discard after’ or ‘Do not use after’ followed In addition to the standard requirements for by a definite date and/or time. . maintained at 15–25 C. 300 mL. Freshly Prepared or that contain an infusion or other vegetable matter. an expiry of 7–14 days * ‘Not to be taken’ and ‘Do not swallow in large would be given to any of the following preparations: amounts’ – This warning must be added to gargles * a solution that does not contain a preservative and mouthwashes. Labelling Remember that because patients frequently misun- The labelling of extemporaneous preparations has derstand the term ‘expiry’ it is suggested that a pre- been covered previously in Chapter 5 (page 91). 100 mL. added to the label of any other preparation that is * ‘For rectal use only’ and ‘Warm to body not intended for administration via the oral route. temperature before administration’ – These warnings should be added to large-volume Further guidance on auxiliary labelling can be enemas. found in Chapter 5 (Table 5. .114 | Pharmaceutical forms and their preparation * ‘Not to be taken’ – This warning should be added * ‘For external use only’ – This warning must be to inhalations and nasal drops.10). tions (see Chapter 6). administered.7 Suspensions Introduction and overview 115 General method for the preparation of a suspension containing an indiffusible solid 119 General principles of suspension preparation 116 Suspensions for external use 119 Diffusible suspensions 116 Inhalations 120 Indiffusible suspensions 117 Lotions 120 Formulation of suspensions 117 Applications 120 Other additives 117 Worked examples 120 Suspensions as 'emergency' formulations 117 Summary of essential principles relating Oral diffusible suspensions 117 to suspensions 127 General method for the preparation of Packaging 128 a suspension containing a diffusible solid 117 Discard dates 128 Oral indiffusible suspensions 119 Labelling 129 Introduction and overview A pharmaceutical suspension is defined as a prep- aration where at least one of the active ingredients is Suspensions are an important pharmaceutical dosage suspended throughout the vehicle. in a suspension at least one of the tility they are often used in situations where an ingredients is not dissolved in the vehicle and so the ‘emergency’ formulation is required (see page 117). In contrast to solu- form that are still widely in use. preparation will require shaking before a dose is Common pharmaceutical products that are sus. Owing to their versa.’ * lotions Suspensions provide a number of distinct advan- * mixtures for oral use. tages and disadvantages compared with other dosage . pensions include: The British Pharmacopoeia (BP) defines oral sus- pensions as: ‘Oral Liquids containing one or more * ear drops active ingredients suspended in a suitable vehicle. * enemas Suspended solids may slowly separate on standing * inhalations but are easily redispersed. * Like all liquid dosage forms. * solved within it. suspensions as dosage forms * Bulky insoluble powders such as Kaolin BP and Advantages Disadvantages Chalk BP can be administered in suspension and Insoluble drugs may be more Preparation requires can act as adsorbents of toxins in the palatable shaking before use gastrointestinal tract. The liquid part of Lotions will leave a cooling layer the suspension evaporates. or only very slightly soluble. leading to potential dosing inaccuracy. in the vehi- them heavy and difficult to transport. * vehicle.116 | Pharmaceutical forms and their preparation forms. Coupled cle but which on shaking disperse evenly throughout with this is the fact that. giving a cooling of medicament on the skin effect to the skin and leaving the thin layer Theoretically possible to formulate sustained-release of powder behind (for example Calamine preparations Lotion BP). This results in two types of pharmaceutical Conditions of storage may adversely affect the suspension: diffusible suspensions and indiffusible disperse system and in the case of indiffusible suspensions. The advantages of suspensions as pharmaceu. * Suspended insoluble powders are easy to Box 7.1 Advantages and disadvantages of swallow. in the aqueous vehicle than the equivalent soluble salt. the vehicle for long enough to allow an accurate dose pharmaceutical liquids are packed in glass to be poured. . they are always Diffusible suspensions much larger and more bulky than their These are suspensions containing light powders that comparable solid formulations. These are obviously prone to breakage tical products are as follows: which can be hazardous and cause the loss of the preparation. solids clumping may occur. The advantages and disadvantages of suspensions * Insoluble derivatives of drugs may be more stable as dosage forms are summarised in Box 7. * Sustained-release preparations can be prepared in suspension (but because of the difficulty of formulation they are rarely encountered). Different pharmaceutical solids The accuracy of the dose is likely to be less than have differing abilities to suspend throughout a with the equivalent solution. difficult to transport equivalent solution). This makes are insoluble. traditionally. Insoluble drugs may be more Accuracy of dose likely to * Suspended drugs will be more rapidly stable be less than equivalent absorbed from the gastrointestinal tract than Suspended insoluble powders solution the equivalent solid dosage form (although are easier to swallow Storage conditions can Enables easy administration of affect disperse system absorption will be slower than from the bulk insoluble powders Bulky. General principles of suspension preparation The disadvantages of suspensions as pharmaceuti- cal products include the following: Although similar to pharmaceutical solutions in a number of ways. bottles. pharmaceutical suspensions differ * in that one or more of the solid ingredients are They must be well shaken prior to measuring a suspended throughout the vehicle rather than dis- dose. * Insoluble derivatives of certain drugs may be more palatable than their soluble equivalent.1. Absorption will be quicker than and prone to container * Lotions that are suspensions leave a thin layer solid dosage forms breakages of medicament on the skin. * Chalk BP Occasionally. Colourings and flavourings are added to suspensions 2 Calculate the quantities of vehicle required to for the same purposes as they are added to solutions dissolve any soluble solids. Examples of indiffusible powders commonly incorporated into pharmaceutical suspensions include: Suspensions as 'emergency' formulations In addition to established formulae. it must always be remembered that tablets Formulation of suspensions and capsules will contain unknown excipients as well The non-soluble ingredients of a suspension are dis. as the nominal quantity of drug. (see page 87). and if possible a pure solutions. Tragacanth Powder BP ening agents. Indiffusible suspensions As with solutions. large amount of finely divided disperse phase in sus- pension. water is normally the vehicle of choice. provide powdered drug to prepare a suspension. of all solids Other additives in the mixture. Double Strength Chloroform Water BP is a commonly used preservative for suspen- These are suspensions containing heavy powders that sions. If a liquid In the preparation of indiffusible suspensions. suspension containing a diffusible solid 1 Check the solubilities. owing to dye adsorption. The bioavailability of persed in the vehicle and.1% w/v). For example. available commercially as a solid dosage form. which is suitable for external use. not disperse evenly throughout the vehicle long which is suitable for internal use. When preparing a suspension from solid dosage forms. the compounder may be main difference from diffusible suspensions is that the expected to prepare a liquid product from the commer- vehicle must be thickened to slow down the rate at cially available solid dosage form.1. and Chlorocresol BP enough to allow an accurate dose to be poured. compounders may * Aspirin BP be required to produce a suitable liquid preparation for * Calamine BP patients who are unable to swallow tablets or capsules. involves crushing of tablets or opening of capsules to tion of a suspending agent. It must be remembered that with the porated into pharmaceutical suspensions include: large surface area of the dispersed powders some of these additives may be adsorbed onto the powder and * Light Kaolin BP – insoluble in water therefore the effective concentration in solution may * Light Magnesium Carbonate BP – very slightly be reduced. Suspensions | 117 Examples of diffusible powders commonly incor. This normally which the powder settles. The increase in the viscosity means that or Compound Tragacanth Powder BP are usually suit- the rate of sedimentation of the insoluble solid will able suspending agents. as with pharmaceutical the drug is likely to be unknown. . the medicament required may only be * Zinc Oxide BP. the preparation is unavailable. in cases where the solid dosage form the viscosity can be changed by the addition of thick. sample of powdered drug should be obtained in order The density of the aqueous vehicle can be altered to produce a suspension without extraneous compo- slightly by the addition of sucrose or glycerol and nents. Other useful preservatives employed in the man- are insoluble in the vehicle and which on shaking do ufacture of suspensions include Benzoic Acid BP 0. in the vehicle. Details of suspending agents have been given Oral diffusible suspensions in Chapter 5. (0. be slower. A summary of the different types of suspending agent used in extemporaneous formula. General method for the preparation of a tion is shown in Table 7. However. is the only source of the drug. This is achieved by the addi.1%. a given concentration of dye soluble in water may produce a paler coloured product when there is a * Magnesium Trisilicate BP – insoluble in water. 1 The 'doubling-up' outlined in the chapter on solutions (Chapter 6). add 9 Transfer the contents of the mortar to a conical these in increasing order of volume as in measure of suitable size. largest volume (powder B) and place on See Powders video for a demonstration of the labelled weighing paper. steps 3. ‘doubling-up’ technique. . technique to ensure complete mixing (see Key 2 Weigh the powder present in the next Skill 7. 8 Add further vehicle in small quantities. 4 and 5 above. 3 Add approximately the same amount of powder B. (These are added now. as 4 Weigh all solids on a Class II or electronic some may be volatile and therefore exposure balance. 6 If further powders are to be added. the mortar and mix with the pestle. is of a pourable consistency. 5 Dissolve all soluble solids in the vehicle in a small glass beaker using the same procedures as Key Skill 7. technique 6 Mix any insoluble diffusible powders in a 1 Weigh the powder present in the smallest porcelain mortar using the ‘doubling-up’ volume (powder A) and place in the mortar.1). as powder A in the mortar. i.118 | Pharmaceutical forms and their preparation Table 7. in the conical measure. 10 Rinse out the mortar with more vehicle and add any rinsings to the conical measure. and doubling the amount of powder in the continue mixing until the mixture in the mortar mortar at each addition. 7 Add a small quantity of the vehicle (which may 4 Mix well with pestle or may not be a solution of the soluble 5 Continue adding an amount of powder B ingredients) to the solids in the mortar and mix that is approximately the same as that in using a pestle to form a smooth paste.e.1 Summary of the different suspending agents used in extemporaneous formulation Category of suspending agent Example of suspending agent Natural polysaccharides (page 85) Acacia Gum BP Agar BP Carrageenan BP Compound Tragacanth Powder BP Guar Gum BP Powdered Tragacanth BP Sodium Alginate BP Starch BP Semi-synthetic polysaccharides (page 86) Hydroxyethylcellulose BP Methyllcellulose BP Sodium Carboxymethylcellulose BP Clays (page 86) Aluminium Magnesium Silicate BP Bentonite BP Magnesium Aluminium Alginate BP Synthetic agents (page 86) Carbomer BP Polyvinyl Alcohol BP Miscellaneous compounds Gelatin BP 3 Prepare any Double Strength Chloroform Water 11 Add remaining liquid ingredients to the mixture BP required. Oral indiffusible suspensions are prepared using the 13 Stir gently. loss caused by powders sedimenting in the 10 Rinse out the mortar with more vehicle and add conical measure (see page 98). same basic principles as for oral diffusible suspensions. transfer to a suitable container. ensuring that all the solid is transferred from the conical measure to the bottle. any rinsings to the conical measure. and container. Suspensions | 119 during mixing needs to be reduced to prevent ‘doubling-up’ technique to ensure complete loss of the ingredient by evaporation. agent of choice will normally be combined with the indiffusible solid using the ‘doubling-up’ technique Point of clarity – method before incorporation into the product. This would prevent any possible transference 1 Check the solubilities in the vehicle of all solids loss caused by powders sedimenting in the in the mixture. ‘doubling-up’ technique. 12 Make up to final volume with vehicle. Alternatively.) 12 Make up to final volume with vehicle.1). conical measure (see page 98). mixture in the conical measure.) mixing (see Key Skill 7. Rinsings from the mortar and other suspension containing an indiffusible liquid ingredients could then be added to the solid bottle before being made up to final volume. See Powders video for a demonstration of the 13 Stir gently. See Suspensions video for a demonstration of 11 Add remaining liquid ingredients to the the preparation of a diffusible suspension. as some may be volatile and therefore exposure during mixing needs to be reduced to prevent loss of the ingredient by Oral indiffusible suspensions evaporation. 9 Transfer the contents of the mortar to a conical This would prevent any possible transference measure of suitable size. and label ready to the addition of a suspending agent. and label ready to be dispensed to the patient. Rinsings from the mortar and other continue mixing until the mixture in the mortar liquid ingredients could then be added to the is a pourable consistency. be transferred directly to a pre-prepared tared 8 Add further vehicle in small quantities. 4 Weigh all solids on a Class II or electronic balance. the contents of the mortar could be transferred directly to a pre-prepared tared General method for the preparation of a container. 2 Calculate the quantities of vehicle required to dissolve any soluble solids. ensuring that all the solid is transferred from the The main difference is that the preparation will require conical measure to the bottle. the contents of the mortar could using a pestle to form a smooth paste. 6 Mix any insoluble indiffusible powders and the Suspensions intended for external use can be com- suspending agent in a porcelain mortar using the pounded using the same basic principles as those . BP required. transfer to a suitable container. 7 Add a small quantity of the vehicle (which may Point of clarity – method or may not be a solution of the soluble ingredients) to the solids in the mortar and mix Alternatively. (These are added now. 5 Dissolve all soluble solids in the vehicle in a Suspensions for external use small glass beaker. The suspending be dispensed to the patient. See Suspensions video for a demonstration of 3 Prepare any Double Strength Chloroform Water the preparation of an indiffusible suspension. bottle before being made up to final volume. 5 mL 1.5 g Concentrated Peppermint Emulsion BP 25 mL 2. They are intended to temperature they may be inhaled directly from a hand.25 mL 3. page 135). der (a diffusible solid) and formulated as a suspension which can then provide an accurate dose to be added to hot (about 65 C) but not boiling water.5 g Light Magnesium Carbonate BP 50 g 5g 2.120 | Pharmaceutical forms and their preparation intended for internal use. they may be dabbed onto the skin surface and volatile ingredient can be adsorbed onto a carrier pow. They are intended to be Inhalations are liquid products that contain volatile applied to the skin. page 105) or emul- as a ‘hot’ inhalation. Alcoholic solutions are also suitable to use also be solutions (see Chapter 6. although they may also be solutions (see Chapter 6.5 g 7. Lotions can be suspensions. There may be differences in Lotions the choice of suspending agent used (see page 85). so that the Applications volatile ingredient is released and inhaled by the Applications can be suspensions. such as Calamine Lotion particularly useful way of effecting this transfer as the BP. In some cases. although they may patient. page 105) or emulsions Inhalations (see Chapter 8.5 g 7. without any dressing or covering material. Worked examples Example 7.5 g 7. without friction. If ingredients are volatile at room sions (see Chapter 8. Shake the Bottle Do not use after (4 weeks) Name of patient Date of dispensing Product formula (British Pharmacopoeia 1988.75 mL Double Strength Chloroform Water BP 500 mL 50 mL 25 mL 75 mL Potable water to 1000 mL to 100 mL to 50 mL to 150 mL Interim formula for Double Strength Chloroform Water BP (see Chapter 2. on a carrier ingredients intended to be released and brought into fabric such as lint and covered with a waterproof contact with the respiratory lining. Suspensions are a dressing.5 g Sodium Bicarbonate BP 50 g 5g 2. page 135). page 32): Concentrated Chloroform 5 mL Water BPC 1959 Potable water to 100 mL . page 740): 1000 mL 100 mL 50 mL 150 mL Magnesium Trisilicate BP 50 g 5g 2. allowed to dry. be applied without friction to the skin and to be used kerchief or absorbent pad.1 Preparation of 150 mL Magnesium Trisilicate Mixture BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Magnesium Trisilicate Mixture BP 150 mL Product directions. it may be simpler to take the calculation through a number of stages.5 mL of vehicle would be required to dissolve the 7. e Visually check that no undissolved chloroform remains at the bottom of the measure. For ease of compounding choose a convenient volume of vehicle. The quantities in the 100 mL product and 50 mL product are then added together to give the quantities of ingredients in a product with a final volume of 150 mL. c Add the measured Concentrated Chloroform Water BPC 1959 to the water in the conical measure. say 90 mL. See Solutions video for a demonstration of the preparation of Double Strength Chloroform Water BP.5 g Sodium Bicarbonate BP on a Class II or electronic balance.5 g Light Magnesium Carbonate BP on a Class II or electronic balance. Therefore a minimum of 82. 5 Weigh 7. accurate measurement of the concentrated component. In the example given above. in which to initially dissolve the solute. Point of clarity – Step 1 Rather than attempt the above conversion in one stage. These quantities are then halved to give a product with a final volume of 50 mL.5 11 ¼ 82. Noting that sodium bicarbonate is soluble 1 in 11 with water.5 g Magnesium Trisilicate BP on a Class II or electronic balance. When choosing the amount of vehicle to use for dissolution.75 mL Concentrated Peppermint Emulsion BP using a 1 mL and 5 mL syringe. measure 5 mL of Concentrated Chloroform water BPC 1959 accurately using a 5 mL conical measure. Method of compounding for Double Strength Chloroform Water BP: a In this case. . d Stir gently and then accurately make up to volume with potable water.5 g is soluble in 82. By using this method.e.5 g of Sodium Bicarbonate BP. 75 mL of Double Strength Chloroform Water BP is required and so it would be sensible to prepare 100 mL. Suspensions | 121 Example 7. 2 Calculate the composition of a convenient quantity of Double Strength Chloroform Water BP. sufficient water to enable dissolution of the concentrated chloroform component without reaching the final volume of the product). As 1 g of sodium bicarbonate is soluble in 11 mL. The final volume of Magnesium Trisilicate Mixture BP required (150 mL) will contain 7. the quantities in the master formula are first divided by 10 to give a product with a final volume of 100 mL. b Add approximately 90 mL of potable water to a 100 mL conical measure (i. To prepare 100 mL Double Strength Chloroform Water BP.5 mL (7. 7. the compounder is less likely to make a calculation error. sufficient to satisfy the formula requirements but also enabling simple.1 Continued Method: 1 Using the master formula from the British Pharmacopoeia for 1000 mL of final product. 3 Weigh 7. a minimum of 11 mL of water would be required to dissolve 1 g of sodium bicarbonate.5 mL). it is important to consider the total amount of each liquid ingredient in the preparation to ensure that only the correct amounts are added or the final product does not go over volume. calculate the quantity of ingredients required to produce the final volume needed (150 mL). 4 Weigh 7. 6 Measure 3.5 g of sodium bicarbonate in this example. 5 g Sodium Bicarbonate BP). . 16 Add the Concentrated Peppermint Emulsion BP to the mixture in the conical measure. continue adding the sodium bicarbonate solution until the paste is pourable. the volume occupied by the powders differs markedly. 9 Stir to aid dissolution. 8 The Sodium Bicarbonate BP (7. it would be incorrect to dissolve the Sodium Bicarbonate BP in 90 mL of Double Strength Chloroform Water BP as the final volume of the preparation only contains 75 mL.5 g) should be added to the vehicle. all the Double Strength Chloroform Water BP is used (75 mL) along with enough potable water to reach the desired volume (approximately 15 mL).1 Continued 7 Accurately measure 75 mL Double Strength Chloroform Water BP using a 100 mL measure. 15 Rinse out the mortar with more sodium bicarbonate solution and add the rinsings to the conical measure. 14 Transfer the contents of the mortar to a 200 mL conical measure. 12 Add a small amount of the sodium bicarbonate solution to the powder in the mortar and mix with a pestle to make a smooth paste. 18 Transfer the solution to a 150 mL amber flat medicine bottle with a child-resistant closure and label. See Suspensions video for a demonstration of the preparation of a suspension. In this case. 17 Make up to volume with any remaining solution and potable water. In this example. as when the 75 mL of Double Strength Chloroform Water BP is added to the preparation. 11 Add the Light Magnesium Carbonate BP to the Magnesium Trisilicate BP in the mortar using the ‘doubling-up’ technique and stir with a pestle to ensure even mixing. The Magnesium Trisilicate BP occupies the smallest volume and therefore is the first powder to be added to the mortar. It is also important not to dissolve the Sodium Bicarbonate BP in 90 mL of potable water. the final volume would be greater than 150 mL. To this add approximately 15 mL potable water in order to produce 90 mL of vehicle. 13 Slowly. which should be poured into a beaker (in order to produce sufficient volume to dissolve the 7. in this example 90 mL of vehicle is required to dissolve the Sodium Bicarbonate BP. 10 Transfer the Magnesium Trisilicate BP to a porcelain mortar. following the principle of adding solutes to solvents.122 | Pharmaceutical forms and their preparation Example 7. Point of clarity – Step 7 As discussed above. It is important to consider the total amount of each liquid ingredient in the product to ensure that only the correct amounts are added. Point of clarity–Steps 10 and 11 The Magnesium Trisilicate BP is added to the mortar first as although the weights of the insoluble solids are identical. 2 Weigh 200 mg Tragacanth BP accurately on a Class II or electronic balance. accurate measurement of the concentrated component.e.5 mL Water BPC 1959 Potable water to 50 mL Method: 1 Calculate the composition of a convenient quantity of Double Strength Chloroform Water BP. b Add approximately 45 mL of potable water to a 50 mL conical measure (i. page 32): Concentrated Chloroform 2. . Method of compounding for Double Strength Chloroform Water BP: a In this case. 3 Weigh 2 g Chalk BP accurately on a Class II or electronic balance.5 mL of Concentrated Chloroform water BPC 1959 accurately using a 5 mL and a 1 mL syringe. sufficient to satisfy the formula requirements but also enabling simple. Suspensions | 123 Example 7. Shake the Bottle Do not use after (4 weeks) Name of patient Date of dispensing Product formula (British Pharmacopoeia 1988. sufficient water to enable dissolution of the concentrated chloroform component without reaching the final volume of the product).4 mL Syrup BP 100 mL 10 mL Double Strength Chloroform Water BP 500 mL 50 mL Potable water to 1000 mL to 100 mL Interim formula for Double Strength Chloroform Water BP (see Chapter 2. 50 mL of Double Strength Chloroform Water BP is required and so it would be sensible to prepare 50 mL. To prepare 50 mL Double Strength Chloroform Water BP. See Solutions video for a demonstration of the preparation of Double Strength Chloroform Water BP.2 Preparation of 100 mL of Chalk Mixture Paediatric BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Paediatric Chalk Mixture BP 100 mL Product directions. measure 2. c Add the measured Concentrated Chloroform Water BPC 1959 to the water in the conical measure. e Visually check that no undissolved chloroform remains at the bottom of the measure. d Stir gently and then accurately make up to volume with potable water. page 724): 1000 mL 100 mL Chalk BP 20 g 2g Tragacanth BP 2g 200 mg Concentrated Cinnamon Water BP 4 mL 0. which may occur with some ingredients. consideration must be given to the properties of the liquid being measured. 14 Make up to volume with any remaining Double Strength Chloroform Water BP and potable water. 8 Add the Chalk BP to the mortar using the ‘doubling-up’ technique to mix the two powders.4 mL Concentrated Cinnamon Water BP using a 1 mL syringe. it is not bad practice to measure the Concentrated Cinnamon Water BP at this stage of the method as loss by evaporation will be avoided by measuring in a syringe. Point of clarity – Step 14 Alternatively a bottle could be tared and the mixture made up to volume in the bottle (see Chapter 5. See Suspensions video for a demonstration of the preparation of a suspension. It must always be remembered that when using a syringe to measure ingredients. This will avoid dissolution of the volume markings from the outside of the syringe. 12 Rinse out the mortar with more Double Strength Chloroform Water BP or potable water and add the rinsings to the conical measure. . 10 Add some of the Double Strength Chloroform Water BP to the paste and mix until pourable. 6 Measure 50 mL of Double Strength Chloroform Water BP in a 50 mL conical measure. Point of clarity – Step 13 The Concentrated Cinnamon Water BP is the last ingredient to be added prior to making up to volume because it is a volatile ingredient. 15 Transfer to an amber flat medicine bottle label and dispense. 11 Transfer the contents to a 100 mL conical measure. or even parts of the syringe itself. They are admixed by the ‘doubling-up’ technique to ensure even mixing and therefore the successful suspension of the indiffusible chalk. 7 Transfer the Tragacanth BP to a porcelain mortar.2 Continued 4 Measure 10 mL Syrup BP in a 10 mL conical measure. Point of clarity–Step 5 Although it is a volatile ingredient. page 98). 13 Add the Concentrated Cinnamon Water BP to the mixture in the conical measure.124 | Pharmaceutical forms and their preparation Example 7. Point of clarity – Steps 7 and 8 The Tragacanth BP is included in the mixture because Chalk BP is an indiffusible solid and therefore it is necessary to add a suspending agent. 9 Add the Syrup BP to the mortar and mix to form a smooth paste. 5 Measure 0. 2 Transfer to a glass mortar. Suspensions | 125 Example 7. 7 Add potable water to the mixture in the mortar to form a pourable suspension. 6 Add to the mortar and mix well.pension. 3 Measure 5 mL Eucalyptus Oil BP in a 5 mL conical measure. page 98). Point of clarity – Steps 3 and 4 Menthol is freely soluble in fixed and volatile oils. Point of clarity – Step 11 Alternatively a bottle could be tared and the mixture made up to volume in the bottle (see Chapter 5. a conical measure could be used. Alternatively. page 577): 1000 mL 100 mL 50 mL Menthol BP 20 g 2g 1g Eucalyptus Oil BP 100 mL 10 mL 5 mL Light Magnesium Carbonate BP 70 g 7g 3.5 g Potable water to 1000 mL to 100 mL to 50 mL Method: 1 Weigh 1 g Menthol BP on a Class II or electronic balance.5 g Light Magnesium Carbonate BP on a Class II or electronic balance. 11 Transfer to a 50 mL amber fluted bottle with a child-resistant closure and label. Care should be taken as the oil will dissolve away the graduation markings on the syringe.3 Preparation of 50 mL of Menthol and Eucalyptus Inhalation BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Menthol and Eucalyptus Inhalation BP 50 mL Product directions. 5 Weigh 3. 8 Transfer the contents of the mortar to a 50 mL conical measure. 10 Make up to volume with potable water. . 9 Rinse the mortar with potable water and add the rinsings to the conical measure. See Suspensions video for a demonstration of the preparation of a sus. Shake the Bottle Not to be Taken Do not use after (4 weeks) Name of patient Date of dispensing Product formula (from the British Pharmacopoeia 1980. 4 Transfer to the mortar and mix with a pestle to dissolve the menthol. Causes drowsiness which may continue the next day. The hospital pharmacy gives you the formula that has been used while the patient was in the hospital: Tabs qs Clobazam 10 mg Concentrated Peppermint Water BP 2% v/v Glycerol BP 6% v/v Syrup BP 25% v/v Suspending agent 2% w/v Freshly boiled and cooled purified water to 100% The patient needs to take 10 mg at each dose and the prescriber wants 30 doses.4 Preparation of a magistral formulation from a hospital formula Example label (assuming a 5 mL dose) (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Clobazam 10 mg/5 mL suspension 150 mL Product directions.3 mL Syrup BP 1.25 mL Compound Tragacanth Powder BP 100 mg Freshly boiled and cooled purified water to 5 mL Name of patient Date of dispensing You receive a prescription for Clobazam liquid. The patient is required to take 10 mg at each dose but unfortunately cannot swallow solid dosage preparations.5 mL Compound Tragacanth Powder BP 100 mg 1g 3g Freshly boiled and cooled purified water to 5 mL to 50 mL to 150 mL . if we make the formula as above such that each 5 mL contains 10 mg Clobazam we would need to prepare 150 mL of suspension. To prepare 150 mL of Clobazam Suspension 10 mg/5 mL: Product formula: 5 mL 50 mL 150 mL Clobazam 10 mg 100 mg 300 mg 1 tablet 10 tablets 30 tablets Concentrated Peppermint Water BP 0. Shake the Bottle Warning. Therefore. If affected.5 mL 37.25 mL 12.1 mL 1 mL 3 mL Glycerol BP 0. Avoid alcoholic drink Do not use after (2 weeks) Each 5 mL contains: Clobazam 10 mg (1 tablet) Concentrated Peppermint Water BP 0. Clobazam is only available commercially as 10 mg tablets.3 mL 3 mL 9 mL Syrup BP 1.1 mL Glycerol BP 0.126 | Pharmaceutical forms and their preparation Example 7. do not drive or operate machinery. the suspension produced would have been unacceptable and more closely related to a solid dosage form than a liquid dosage form. 7 Add the Glycerol BP to the powders in the mortar and mix to make a paste.4 Continued Freshly boiled and cooled purified water is used as the vehicle as no preservative is included in the preparation. 6 Transfer the powder to a porcelain mortar and add the Compound Tragacanth Powder BP using the ‘doubling-up’ technique. this sec- relating to suspensions tion contains: * further notes on the packaging of This section recaps the main principles relating to sus. 3 Measure 9 mL of glycerol using a 10 mL conical measure. extemporaneously prepared suspensions pensions that have been covered in other sections of * specific points relevant to the expiry of the book. 12 Measure 3 mL Concentrated Peppermint Water BP using a 5 mL conical measure. Suspensions | 127 Example 7. 10 Rinse out the mortar with more syrup and freshly boiled and cooled purified water. Summary of essential principles extemporaneous preparation of suspensions. label and dispense to the patient. Mix with the pestle.5 mL Syrup BP using a 50 mL measure and a suitably graduated 5 mL syringe.2%. 8 Add the Syrup BP to the mortar to make a pourable paste. Tragacanth BP itself is normally used in concentrations of 0. See Suspensions video for a demonstration of the preparation of a suspension. 13 Add the Concentrated Peppermint Water BP to the mixture in the conical measure. therefore had Tragacanth BP been used in a 2% strength. Point of clarity – Step 2 As the quantity of suspending agent required was indicated to be 2%. 4 Measure 37. Compound Tragacanth Powder BP was chosen as the suspending agent as this is a suitable quantity to include to produce a reasonable suspension. Method: 1 Count out 30 Clobazam tablets. To assist compounders in understanding the extemporaneously prepared suspensions . 15 Stir and transfer to a 150 mL amber flat medicine bottle with a child-resistant closure. 14 Make up to volume with freshly boiled and cooled purified water. 2 Weigh 3 g Compound Tragacanth Powder BP using a Class II or electronic balance. 9 Transfer the contents of the mortar to a 200 mL conical measure. 5 Transfer the tablets to a glass mortar and grind them to make a smooth powder. 11 Add rinsings to the mixture in the conical measure. for official preparations the sions. An overview of Discard dates the main considerations for the packaging of suspen. 150 mL. Obviously it is important not to use of two weeks is applied to oral suspensions that need a size of container that is too large for the volume of to be Freshly Prepared or that contain an infusion or preparation to be dispensed.2 Summary of packaging for pharmaceutical suspensions Oral liquids Amber flat medicine bottle (Typical sizes: 50 mL. External preparations * ‘Freshly Prepared’ refers to a preparation that has should be packaged in fluted amber bottles (i. stored for a period greater than four weeks when Pharmaceutical bottles come in a variety of dif- maintained at 15–25 C. 200 mL. A four-week expiry should be appearance issues. texts. enable simple identification. Guidelines on the packaging of extemporaneously prepared suspensions are summarised in Table 7. This will for use. Liquid preparations that are useful when extemporaneously compounding are intended for the oral route should be packed in suspensions: plain (smooth) amber bottles. by both sight and touch. 100 mL. When select. consideration should be given to the route or British Pharmacopoeia employs two definitions that method of administration. As with solutions.128 | Pharmaceutical forms and their preparation Table 7. 300 mL and 500 mL) Pharmaceutical product examples include:Mixtures (suspensions) for oral use External liquids Amber fluted medicine bottle (Typical sizes: 50 mL. page 111). as both preparation preparations will be advised via the relative official types are based on liquid administration.e. ferent sizes and it is important to choose a suitably sized container to match the volume of preparation In practical terms it is suggested that an expiry date to be dispensed. a dose is measured. 100 mL. Consideration should be given applied to oral suspensions that need to be Recently to selecting a bottle that will leave sufficient space Prepared.2. Discard dates for pharmaceutical suspensions typi- sions will be given here. Packaging The packaging of extemporaneous preparations has been covered previously (page 97). . cally mirror those for pharmaceutical solutions The packaging for suspensions is based on the (see Chapter 6. * ‘Recently Prepared’ should be applied to of preparations that are not to be taken via the oral compounded items that are likely to deteriorate if route. 20 mL) Pharmaceutical product examples include: Ear drops Nose drops * additional key points related to the labelling of to allow the product to be shaken adequately before pharmaceutical suspensions. The discard date of official same principles as for solutions. 200 mL) Pharmaceutical product examples include: Applications Inhalations Lotions Amber fluted medicine bottle with dropper top (Typical sizes: 10 mL. ing packaging for extemporaneously prepared suspen. for both cost and other vegetable matter. amber been compounded less than 24 hours prior to issue bottles with vertical ridges or grooves). 10). found in Chapter 5 (Table 5. In addition to the standard requirements for the When dealing with unofficial preparations. Labelling derstand the term ‘expiry’ it is suggested that a pre. . an expiry of 7–14 days would be given to any of * ‘Shake the bottle’ – All suspensions will require the following preparations: this additional label. added to the label of any other suspension not intended for administration via the oral route. As a general ing points need to be taken into consideration: rule. The labelling of extemporaneous preparations has ferred method of indicating shelf-life on the label of been covered in Chapter 5 (page 92). Suspensions | 129 Remember that because patients frequently misun. available * ‘For external use only’ – This warning must be * a new suspension or ad hoc preparation. * a suspension that does not contain a preservative * ‘Not to be taken’ – This warning must be added to * a suspension where there are no stability data the label of any inhalations. Further guidance on expiry dates for pharma- ceutical preparations can be found in Chapter 5 Further guidance on auxiliary labelling can be (page 92). the follow- compounder must consider the following. An overview of extemporaneously compounded products is to apply the main considerations for the labelling of suspen- the term ‘Discard after’ or ‘Do not use after’ followed sions will be given here. by a definite date and/or time. the labelling of extemporaneous preparations. . via tinuous phase).g.e. that reflects their use (e. application. as the oily phase is usually less tions for external use are always given a different title pleasant to take and more difficult to flavour.).8 Emulsions Introduction and overview 131 Creaming 137 Formulation of emulsions 133 Phase inversion 137 Continental and dry gum methods 133 Emulsions for external use 137 Calculation of the amount of emulsifying Vehicles used in the preparation of external agent to be used in the preparation of emulsions 137 an emulsion using the dry gum method 134 Preservatives used in the preparation Wet gum method 135 of external emulsions 137 General method of preparation of an emulsion Emulsifying agents used in the preparation of using the dry gum method 135 external emulsions 137 Preparation of the primary emulsion 136 Worked examples 138 Dilution of the primary emulsion 136 Summary of essential principles relating to emulsions 151 Problems encountered when making the primary emulsion 136 Packaging 151 Stability of emulsions 136 Discard dates 151 Cracking 136 Labelling 151 Introduction and overview globules (Figure 8. either or . This type of emulsion is termed an ‘oil-in-water’ emulsion. Oral Emulsions are Oral Liquids containing The emulsifying agent ensures that the oil phase is one or more active ingredients. lotion.1). An emulsion is essentially a liquid preparation con. to be ‘oil in water’. Emulsion formula. cream. According to the British Pharmacopoeia (BP): taining a mixture of oil and water that is rendered homogeneous by the addition of an emulsifying agent. Generally all oral dose emulsions tend the oral route of administration). to be those with external uses. They are finely dispersed throughout the water as minute stabilised oil-in-water dispersions. ‘Water-in-oil’ emulsions can be formed. The oily phase (disperse The pharmaceutical term ‘emulsion’ is solely used to phase) is dispersed through the aqueous phase (con- describe preparations intended for internal use (i. but these tend etc. agent specified in individual monographs may * Conditions of storage may adversely affect the be reduced to yield a preparation of suitable disperse system.1. and in addition the patient will Extemporaneous preparation need counselling on the use of the measuring In Oral Emulsions prepared according to the device. Solids may also be suspended in Oral Although not a major disadvantage. bulky than their comparable solid formulation. cod preparation. * They are liable to microbial contamination which * An oil-soluble drug can be dissolved in the can lead to cracking (see page 135). difficult to transport and The disadvantages of emulsions as pharmaceutical removed prone to container breakages products are as follows: Increased rate of absorption Liable to microbial Possible to include two contamination which can lead * They must be shaken well prior to measuring a incompatible ingredients. traditionally. The efficient absorption Advantages Disadvantages of the oil is increased by a process of Unpalatable drugs can be Preparation needs to be homogenisation which reduces the size of the oil administered in palatable shaken well before use form Measuring device needed for globules. whereby fats are emulsified in the duodenum by bile salts. dosage forms. maceutical products are as follows: These are obviously prone to breakage which can * A dose of an unpalatable drug may be be hazardous and cause the loss of the administered in a palatable liquid form (e. and even after efficient shaking the accuracy one in each phase of the of the dose is likely to be less than with equivalent emulsion solutions. Coupled tages associated with the use of emulsions as oral with this is the fact that. * The aqueous phase can be easily flavoured. the quantity of emulsifying measure a dose. The advantages of emulsions as phar- pharmaceutical liquids are packed in glass bottles. formula and directions given for Extempora. to cracking dose.132 | Pharmaceutical forms and their preparation both phases of which may contain dissolved * A measuring device is needed for administration. * Emulsification increases the absorption of fats Box 8. leading to creaming or cracking consistency provided that by so doing the of the emulsion (see page 135). it must be Emulsions. they are much more affected.1 Advantages and disadvantages of through the intestinal wall. . flavoured stability Oily sensation easily Bulky. dosage forms are summarised in Box 8. * Some degree of technical accuracy is needed to neous preparation. When issued for use. borne in mind that a measuring device will need to sions should be supplied in wide-mouthed be supplied to the patient in order for them to be bottles. able to measure an accurate dose (this will have cost implications). disperse phase and be successfully administered to The advantages and disadvantages of emulsions as a patient in a palatable form. solids. Consider the process emulsions as dosage forms of fat digestion.g. liver oil emulsion). Unpalatable oil-soluble administration * Liquid dosage forms of incompatible ingredients drugs can be administered in Need a degree of technical may be formulated by dissolving or suspending palatable form accuracy to measure a dose each ingredient in one of the phases of an emulsion Aqueous phase easily Storage conditions may affect system. This makes emulsions heavier and more difficult There are a number of advantages and disadvan- to transport than solid dosage forms. Oral Emul. * The texture/consistency of the product is improved as the ‘oily’ sensation in the mouth is successfully masked by the emulsification process. stability of the preparation is not adversely * Like all liquid dosage forms. g. water rather than potable water (see Examples 8. The quantity Extemporaneously prepared emulsions for oral of emulsifying agent added is determined by the administration are usually made by the Continental type of oil to be emulsified and the quantity of or the dry gum method. con- as Double Strength Chloroform Water BP at taining added flavouring or colourings as required.2–8. * A preservative (usually added to the product emulsions will have in the formulation a vehicle. an emulsion will also need an emulsi- using freshly boiled and cooled purified fying agent (or emulgent). If freshly There is also the need for a preservative. The only difference between the Continental and dry gum methods is the proportions of constitu- The theory of emulsification is based on the study of ents within the primary emulsion (for example. the Internal emulsions prepared by the dry gum principal considerations are the same. use a ratio of 4:3:2 rather than 4:2:1 with the dry gum ules. . by mixing the emulsifying gum (usually Acacia BP) * Additional flavouring if required. with the oil. milk. The object is to method should contain. in the form of Double Strength vehicle. Oil (disperse phase) Thin layer of emulsifying agent Water (continuous phase) Figure 8. emulsified. suspended in method – see page 134). will be seen to consist of fatty glob. Acacia BP).1 Illustration of an oil-in-water emulsion. if oil emulsions made by the Continental method would examined closely. it would be appropriate to manufacture Chloroform Water BP.1). water. Continental and dry gum methods * An emulsifying agent (or emulgent). As with other liquid preparations for oral use. and finally suspend the globules water is normally used because of the increased in the aqueous phase (see Figure 8. the Double Strength Chloroform Water BP In addition. surrounded by a layer of casein. When a pharmaceutical emulsion is made. in addition to the oil to be completely divide the oily phase into minute globules. Emulsions | 133 Formulation of emulsions phase. risk from microbial contamination. 50% of the volume of the vehicle). the following ingredients: surround each globule with an envelope of suspending * A vehicle – freshly boiled and cooled purified agent (e. fixed the most naturally occurring emulsion. where the emulsion is formed emulsion to be prepared.6). Milk. which is then mixed with the aqueous * Additional colouring if required. which is boiled and cooled purified water is used as the usually chloroform. 2 predominantly lipophilic it will favour the production Triethanolamine oleate 12. Sodium oleate 18. Gum 1 part by weight . where it is positioned Sodium lauryl sulphate 40. if it is Tragacanth 13.2 Hydrophil–lipophil balance (HLB) value mine how effective they are under various conditions of a number of common emulsifying agents of use. where high HLB numbers indicate hydrophilic properties and low HLB numbers indicate Calculation of the amount of emulsifying lipophilic properties (Table 8. mineral oils agent is allocated an HLB number (see Table 8.0 If an emulsifying agent is predominantly hydrophilic an oil-in-water emulsion is formed. finely divided solids have been used Table 8. 13–15 Detergents The colloidal clays are mainly used as emulsion sta- bilisers for external lotions or creams. fixed oils. If an emulsifying agent was too hydro- philic it would dissolve completely in the aqueous Polysorbate 20 16. 15–16 Solubilisers minium and magnesium hydroxide have both been used as emulsifying agents for preparations intended for internal use. The ideal emulsifying agent must concentrate predominantly at the interface Polysorbate 80 15. originally for non-ionic surface active The amount of emulsifying agent used is dependent on agents. alu. Emulsifying agent HLB value All emulsifying agents will contain a water- attracting or hydrophilic part and an oil-attracting or Acacia 8. but has been expanded to include cationic the amount and type of oil to be emulsified.134 | Pharmaceutical forms and their preparation Occasionally. HLB range Application minium hydroxide. Colloidal clays such as bentonite. whereas those that are preferentially wet. whereas alu. Oils can be and anionic surface active agents. Each emulsifying divided into three categories.7 phase and if it was too lipophilic it would totally dis. agent to be used in the preparation of an The HLB system was developed by W C Griffin emulsion using the dry gum method in 1949.2 for and aromatic (volatile) oils.9 solve in the oily phase.1). Fixed oils: When several oils or fats are included in a prepa.6 When an emulsifying agent displays these properties it Sorbitan monostearate 4. examples).0 such that the hydrophilic portion is in the aqueous phase and the lipophilic portion is in the oily phase. Sorbitan monolaurate 8. Conversely. The solid must possess a balance (HLB) ranges and their applications of hydrophilic and hydrophobic properties.1 Different hydrophil–lipophil balance to form emulsions. If the chosen powder is 7–9 Wetting agents easily wetted by water then an oil-in-water emulsion is formed.7 is said to have the proper hydrophil–lipophil balance. The hydrophil–lipophil balance (HLB) of surface active agents has been categorised into the HLB system of numbering.0 of a water-in-oil emulsion. Polysorbate 60 14.0 between oil and aqueous phases.0 lipophilic part. All emulsifying agents will exhibit certain physical and chemical characteristics that will deter. 8–18 Oil-in-water emulsifying agents ted by the oil phase produce water-in-oil emulsions. magnesium hydroxide. Oil 4 parts by volume ration a blend of emulsifying agents is sometimes Aqueous phase 2 parts by volume employed to produce the best product. Table 8. magnesium oxide and silica gel are some of the insoluble substances that have been 3–6 Water-in-oil emulsifying agents used as emulsifying agents. the mixture is triturated until a in a failed product. When nearly all the oil has been added. adding extra small amounts of water when necessary. This can be rectified by the an emulsion using the dry gum addition of slightly more water. dry equipment – All equipment should be gum in a primary emulsion thoroughly cleaned. making the primary emulsion to prevent the emulsion Therefore 4 parts would be equivalent to breaking down on storage or dilution. Ingredients for the primary Volatile Cinnamon Oil BP 2 2 1 emulsion should all be weighed and measured Peppermint Oil BP before starting to make the product. Therefore 2 parts would be equivalent to Wet gum method 10 mL aqueous phase. When all the It is relatively easy for an emulsion to crack. . rinsed with water and dried carefully before use. 20 mL of oil. The formula for the primary emulsion ence is in the method of preparation. would therefore be: Using this method the acacia powder would be Fixed oil 20 mL added to the mortar and then triturated with the water Aqueous phase 10 mL Gum 5g until the gum was dissolved and a mucilage formed. Accurate weighing and measuring of the compo. same as those used in the dry gum method. * Accurate quantities – Accurate quantities are Fixed Arachis Oil BP 4 2 1 essential. allow oil to Cod Liver Oil BP drain from measure). water and emulsifying agent Therefore 1 part would be equivalent to 5 g for the preparation of the primary emulsion are the of gum. It also means that the reasons for Oil 2 parts by volume failure outlined below when using the dry gum method Aqueous phase 2 parts by volume have been eliminated. The proportions of oil. It Aqueous phase 2 parts by volume should be noted that there is less chance of failure with Gum 1 part by weight this method provided the oil is added very slowly and Aromatic (volatile) oils: in small quantities. Gum 1 part by weight These proportions are important when making the primary emulsion.3 Ratio of oily phase to aqueous phase to * Clean. Emulsions | 135 Mineral oils: In the main this method has fallen out of favour as Oil 3 parts by volume it takes much longer than the dry gum method. The differ.g.3. the resulting mixture in the mortar may appear a little poor with some of the oil General method of preparation of appearing to be absorbed. Remember the following points are smooth primary emulsion is obtained. Check weighing/measuring technique Castor Oil BP and minimise transference losses (e. resulting oil has been added. be required to produce 100 mL of a The quantities for primary emulsions (in parts) are 20% emulsion of a fixed oil? summarised in Table 8. to prevent the emulsion breaking Example 8. * Have all ingredients ready – Correct rate of Mineral Liquid Paraffin BP 3 2 1 addition is important. The trituration con- method tinues until all the oil has been added. For a 20% emulsion 20 mL of the oil in 100 mL nents in the primary emulsion are important when of emulsion would be required.1 What quantities would down on dilution or storage. particularly measures. critical when preparing emulsions: Table 8. Type Examples Oil Aqueous Gum of oil mortars and pestles. The oil would then be added to the mucilage drop by drop while triturating continuously. ing or phase inversion (Table 8. oil in water. Creaming – Lack of stability of The emulsion will 2 Transfer emulsion to a measure. reform on shaking Add other liquid ingredients if necessary and emulsion into two Product not make up to the final volume.136 | Pharmaceutical forms and their preparation The preparation of an emulsion has two main * inaccurate measurement of water or oil components: * cross-contamination of oil and water * use of a wet mortar * Preparation of a concentrate called the ‘primary * excessive mixing of the oil and gum emulsion’. which may denature This is the term applied when the disperse phase coa- the emulsifying agent and result in a poor product. one homogeneous containing more of See Emulsions video for a demonstration of the the disperse phase preparation of an emulsion. with rinsings. w/o. Reasons for this include: o/w. for problem be saved? Mix carefully with the pestle in one direction. Mix lightly with the pestle. allowing all the oil to drain out. Change of disperse phase into storage and the contents of the mortar may become oily. . Then mix vigorously. 2 Measure the quantity of aqueous vehicle required Stability of emulsions for the primary emulsion. water in oil. emulsion. * insufficient shear between the head of the pestle Preparation of the primary emulsion and the mortar base * too early or too rapid dilution of the primary 1 Measure the oil accurately in a dry measure. Oil globules/slicks should not be apparent. Cracking can occur if the oil turns with a shearing action in one direction. Table 8. cream. Transfer the oil into a large dry porcelain mortar. From o/w to w/o or disperse phase not reform on from w/o to o/w greater than 74% shaking ous vehicle. Re-dispersion can- 4 Add all of the required aqueous vehicle in one not be achieved by shaking and the preparation is no addition. The product has failed and must be restarted. Caution – overmixing generates heat. Separation of the the system. just Cracking sufficient to disperse any lumps. rancid during storage. using the pestle longer an emulsion. cream- reach. 3 Weigh the emulsifying agent and place on the oil in the mortar. Increased degree of whiteness indicates a better quality product. The product should be a thick white cracked emulsion. causing the two phases to separate. lesces and forms a separate layer. not reform on Problems encountered when making the disperse phase Decomposition of shaking primary emulsion coalesce and there the emulsifying The primary emulsion does not always form correctly is separation of the agent. This is because of phase inversion. Place this within easy Emulsions can break down through cracking. The oil-in-water emulsion has become a water-in-oil Phase inversion – Amount of The emulsion will emulsion that cannot be diluted further with the aque.4 Summary of the problems encountered Dilution of the primary emulsion in emulsion preparation 1 Dilute the primary emulsion drop by drop with very Problem Possible reason Can the emulsion small volumes of the remaining aqueous vehicle. * poor-quality acacia * Dilution of the concentrate. regions. thin a separate layer temperature and translucent.4). The acid formed denatures the 5 When the product becomes white and produces a emulsifying agent. ‘clicking’ sound the primary emulsion has been See Emulsions video for an example of a formed. Cracking – The Incompatible The emulsion will globules of the emulsifying agent. Dimethicone (Dimeticone) BP. adequately shaken there is a risk of the patient obtain- ing an incorrect dose. As the concentration of the disperse in the extemporaneous formulation and production phase approaches a theoretical maximum of 74% of of creams (see Chapter 5. * Synthetic surface active agents with low HLB Water-miscible vehicles values. The preservatives commonly used in emulsions for If the disperse phase exceeds this the stability of the emul- external use are the same as those commonly employed sion is questionable. * Water – Usually freshly boiled and cooled purified Oil-in-water emulsifiers water to reduce the chances of any microbial contamination. Emulsifying agents used in the tion to the skin and may be liquid or semi-liquid in preparation of external emulsions consistency. This is undesirable as the Oily vehicles product appearance is poor and if the product is not * Mineral oils – e. Benzoic Acid BP 0.1% Chlorocresol BP 0.g. * Wool alcohol – Preferable to wool fat as it is purer but still has the problem of creating unpleasant Vehicles used in the preparation of odours in warm weather. on the top of a pint of milk). The consistency of the water-in-oil emulsifier. but it usually remains in globules the product. the oil separates out. used as an emulsion stabiliser. . phase inversion is more likely to occur. page 80). Coconut Oil the viscosity of the continuous phase is increased.g. The problem with these oils is Phase inversion that they tend to go rancid. Mainly and liniments are either water miscible or oily. forming a layer on sometimes added to increase the cooling effect of top of the emulsion. owing to the evaporation of the so that it can be re-dispersed on shaking (e. it is not a very good formed emulsion determines whether it is a lotion or emulsifier and nowadays tends to be used as an a much thicker cream product. * Vegetable oils – e. Alcohol is In creaming. namely: the total volume. Creaming is less likely to occur if Liquid Paraffin BP. external emulsions * Wool fat – Similar to human sebum and can cause Vehicles commonly used in the preparation of lotions sensitisation problems in some patients. the cream alcohol from the skin’s surface. Light Liquid Paraffin BP. Olive Oil BP.1% Emulsions for external use Cetrimide BP 0. This is the process when an oil-in-water emulsion changes to a water-in-oil emulsion or vice versa. * Synthetic oils – e.01% Emulsions for external use are designed for applica. see Chapter 9. For Preservatives used in the preparation of stability of an emulsion. emulsion as an external application is that it is easily * Calcium soaps – Made in situ by mixing a fatty spread over the skin and usually easily removed by acid and calcium hydroxide solution (lime water). Arachis Oil BP. the optimum range of concen. The advantage of an emulsion stabiliser.002–0. external emulsions tration of dispersed phase is 30–60% of the total volume. washing. * Emulsifying waxes: * Alcohol – Industrial methylated spirit (IMS) is the – Anionic – Emulsifying wax BP normal alcoholic constituent of products for – Cationic – Cetrimide Emulsifying Wax BP external use as it is exempt from excise duty and – Non-ionic – Cetomacrogol Emulsifying Wax BP.g. both oil-in-water and water-in-oil emulsions Water-in-oil emulsifiers can be produced and applied to the surface of the skin * Beeswax – Occasionally used and is a traditional and mucous membranes. no primary emulsion is formed. Emulsions | 137 Creaming therefore cheaper than ethanol. The formulation of external emulsions The range of emulsifying agents used is described in differs from that of conventional emulsions in that full in Chapter 5 (page 87).g. BP. As with internal emul- sions. For further information. One part will therefore be 60 4 = 15.g. Shake the Bottle Do not use after (4 weeks) Each 10 mL contains: Cod Liver Oil BP 3 mL Acacia BP 0. lotions and liniments are often liquid emulsions. applica- an oil-in-water emulsifying agent. Worked examples Example 8.138 | Pharmaceutical forms and their preparation * Soaps: * Synthetic surface active agents with a high HLB – Soft soap – sticky green material that produces value. The amount of acacia required ¼ 15 g. Other than creams that are thick emulsions. tions. Turpentine The emulsifying agents used for emulsions for Liniment BP) internal use.2 The preparation of a magistral formulation of 200 mL of Cod Liver Oil 30% emulsion from a doctor's prescription Example label (assuming a 10 mL dose) (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Cod liver oil 30% v/v emulsion 200 mL Product directions. . would – Ammonium soaps formed during the preparation not be suitable for an emulsion for external use as they of products when the oleic acid and ammonium are too sticky. namely tragacanth and acacia. the primary emulsion ratio is: Oil : Water : Gum 4:2:1 In this case 60 mL of Cod Liver Oil BP is required. compounds react to produce ammonium oleate. an oil-in-water emulsion (e. As cod liver oil is a fixed oil. therefore 4 parts ¼ 60 mL. Therefore.75 g Double Strength Chloroform Water BP 5 mL Freshly boiled and cooled purified water to 10 mL Patient name Date of dispensing Product formula: Master (100 mL) 200 mL Cod Liver Oil BP 30 mL 60 mL Acacia BP qs qs Double Strength Chloroform Water BP 50 mL 100 mL Freshly boiled and cooled purified water to 100 mL to 200 mL First it is necessary to calculate the quantity of emulsifying agent (acacia) required to produce 200 mL of the emulsion. the amount of freshly boiled and cooled purified water needed is 2 15 mL ¼ 30 mL. c Add the measured Concentrated Chloroform Water BPC 1959 to the water in the conical measure. sufficient to satisfy the formula requirements but also enabling simple. d Stir gently and then accurately make up to volume with freshly boiled and cooled purified water. sufficient water to enable dissolution of the concentrated chloroform component without reaching the final volume of the product). See Solutions video for a demonstration of the preparation of Double Strength Chloroform Water BP.2 Continued Therefore the product formula for 200 mL of Cod Liver Oil 30% emulsion is: 200 mL Cod Liver Oil BP 60 mL Acacia BP 15 g Double Strength Chloroform Water BP 100 mL Freshly boiled and cooled purified water to 200 mL Interim formula for Double Strength Chloroform Water BP (see Chapter 2. Point of clarity – Method Remember the accurate preparation of the primary emulsion is crucial for the full emulsion to be satisfactorily produced. Emulsions | 139 Example 8. Method of compounding for Double Strength Chloroform Water BP: a In this case. accurate measurement of the concentrated component. freshly boiled and cooled purified water is used here as emulsions are susceptible to microbial contamination. measure 5 mL of Concentrated Chloroform water BPC 1959 accurately using a 5 mL conical measure. Primary emulsion: Cod Liver Oil BP 60 mL Double Strength Chloroform Water BP 30 mL Acacia BP 15 g . 100 mL of Double Strength Chloroform Water BP is required. To prepare 100 mL Double Strength Chloroform Water BP.e. page 32): Concentrated Chloroform Water BPC 1959 5 mL Freshly boiled and cooled purified water to 100 mL Method: 1 Calculate the composition of a convenient quantity of Double Strength Chloroform Water BP. Point of clarity – Step b Although potable water would usually be used in the manufacture of Double Strength Chloroform Water BP. e Visually check that no undissolved chloroform remains at the bottom of the measure. b Add approximately 90 mL of freshly boiled and cooled purified water to a 100 mL conical measure (i. Remember. the whiter the primary emulsion the better it is formed. 3 Accurately measure 100 mL Double Strength Chloroform Water BP using a 100 mL measure. Point of clarity – Step 10 The Double Strength Chloroform Water BP needs to be added to the primary emulsion drop by drop until it is pourable to ensure that the primary emulsion does not crack. freshly boiled and cooled purified water is used here as emulsions are susceptible to microbial contamination. See Emulsions video for a demonstration of the preparation of an emulsion. . 4 Accurately measure 60 mL Cod Liver Oil BP in a conical measure. Point of clarity – Step 9 A characteristic clicking sound will be heard when the primary emulsion is formed. Point of clarity – Step 5 Ensure the measure is well drained as the quantities to be used are critical in the formation of the primary emulsion. 9 Stir vigorously with the pestle in ONE direction only until the primary emulsion is formed. 8 Add the 30 mL of Double Strength Chloroform Water BP to the mortar in one go. 7 Transfer the Acacia BP to the mortar and stir gently (approximately three stirs).2 Continued 2 Weigh 15 g of Acacia BP on a Class II or electronic balance. 5 Transfer the Cod Liver Oil BP to a clean dry porcelain mortar. Point of clarity – Step 12 Even though there is a preservative in the preparation. 11 Transfer to an appropriate conical measure with rinsings.140 | Pharmaceutical forms and their preparation Example 8. Gentle stirring is required to ensure that there is no heat production that might denature the gum and prevent the formation of the emulsion. 13 Stir and transfer to an amber flat medicine bottle. label and dispense to the patient. 6 Measure 30 mL of Double Strength Chloroform Water BP (from the 100 mL measured in Step 3). 10 Add more Double Strength Chloroform Water BP to the primary emulsion until the emulsion is pourable. Point of clarity – Step 7 This step is to wet the Acacia BP. 12 Make up to volume with any remaining Double Strength Chloroform Water BP and freshly boiled and cooled purified water. Example label (assuming a 15 mL dose) (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Arachis oil 40% v/v emulsion 150 mL Product directions.5 mL Freshly boiled and cooled purified water to 15mL Patient name Date of dispensing Product formula: Master (100 mL) 50 mL 150 mL Arachis Oil BP 40 mL 20 mL 60 mL Acacia BP qs qs qs Concentrated Peppermint Emulsion BP qs qs 2. therefore 4 parts ¼ 60 mL.25 mL Double Strength Chloroform Water BP 7. The amount of Acacia BP required ¼ 15 g. page 90) is a suitable flavouring and the dose is 0. Therefore. One part will therefore be 60 4 ¼ 15. Concentrated Peppermint Emulsion BP (see Chapter 5. which means each individual dose is 15 mL.25 ¼ 2. The amount of Concentrated Peppermint Emulsion BP that would be suitable to use would be 10 0. The dose of the emulsion is 15 mL bd.25–1 mL. Shake the Bottle Do not use after (4 weeks) Each 15 mL contains: Arachis Oil BP 6 mL Acacia BP 1.5 mL. therefore in 150 mL there would be 10 doses.3 Preparation of a magistral formulation of 150 mL of Arachis Oil BP 40% emulsion with a peppermint flavouring from a doctor's prescription Before deciding the formula for the emulsion.5 mL Double Strength Chloroform Water BP 50 mL 25 mL 75 mL Freshly boiled and cooled purified water to 100 mL to 50 mL to 150 mL First it is necessary to calculate the quantity of emulsifying agent (Acacia BP) required to produce 150 mL of the emulsion. the amount of freshly boiled and cooled purified water needed is 2 15 mL ¼ 30 mL. Emulsions | 141 Example 8. the primary emulsion ration is: Oil : Water : Gum 4:2:1 In this case 60 mL of Arachis Oil BP is required. As Arachis oil is a fixed oil. .5 g Concentrated Peppermint Emulsion BP 0. the type and quantity of flavouring must be decided upon. d Stir gently and then accurately make up to volume with freshly boiled and cooled purified water. accurate measurement of the concentrated component. To prepare 100 mL Double Strength Chloroform Water BP. 75 mL of Double Strength Chloroform Water BP is required and so it would be sensible to prepare 100 mL. Point of clarity – Step b Although potable water would usually be used in the manufacture of Double Strength Chloroform Water BP. sufficient to satisfy the formula requirements but also enabling simple. e Visually check that no undissolved chloroform remains at the bottom of the measure. Method of compounding for Double Strength Chloroform Water BP: a In this case.5 mL Double Strength Chloroform Water BP 75 mL Freshly boiled and cooled purified water to 150 mL Interim formula for Double Strength Chloroform Water BP (see Chapter 2. sufficient water to enable dissolution of the concentrated chloroform component without reaching the final volume of the product).3 Continued Therefore the product formula for 150 mL of Arachis Oil BP 40% emulsion is: 150 mL Arachis Oil BP 60 mL Acacia BP 15 g Concentrated Peppermint Emulsion BP 2. b Add approximately 90 mL of freshly boiled and cooled purified water to a 100 mL conical measure (i. page 32): Concentrated Chloroform Water BPC 1959 5 mL Freshly boiled and cooled purified water to 100 mL Method: 1 Calculate the composition of a convenient quantity of Double Strength Chloroform Water BP. freshly boiled and cooled purified water is used here as emulsions are susceptible to microbial contamination. See Solutions video for a demonstration of the preparation of Double Strength Chloroform Water BP. . c Add the measured Concentrated Chloroform Water BPC 1959 to the water in the conical measure.e. measure 5 mL of Concentrated Chloroform water BPC 1959 accurately using a 5 mL conical measure.142 | Pharmaceutical forms and their preparation Example 8. Point of clarity – Method Remember the accurate preparation of the primary emulsion is crucial for the full emulsion to be satisfactorily produced. 3 Continued Primary emulsion: Arachis Oil BP 60 mL Double Strength Chloroform Water BP 30 mL Acacia BP 15 g 2 Weigh 15 g of Acacia BP on a Class II or electronic balance. Point of clarity – Step 5 Ensure the measure is well drained as the quantities to be used are critical in the formation of the primary emulsion. 9 Stir vigorously with the pestle in ONE direction only until the primary emulsion is formed. 6 Measure 30 mL of Double Strength Chloroform Water BP (from the 75 mL measured in Step 3). 8 Add the 30 mL of Double Strength Chloroform Water BP to the mortar all in one go. Gentle stirring is required to ensure that there is no heat production that might denature the gum and prevent the formation of the emulsion. 10 Add more Double Strength Chloroform Water BP to the primary emulsion until the emulsion is pourable. 13 Add the Concentrated Peppermint Emulsion BP to the emulsion in the conical measure. 3 Accurately measure 75 mL Double Strength Chloroform Water BP using a 100 mL measure. Point of clarity – Step 10 The Double Strength Chloroform Water BP needs to be added drop by drop to the primary emulsion until it is pourable to ensure that the primary emulsion does not crack. 5 Transfer the Arachis Oil BP to a clean dry porcelain mortar. Remember. the whiter the primary emulsion the better it is formed.5 mL of Concentrated Peppermint Emulsion BP using an appropriate syringe. Emulsions | 143 Example 8. 11 Transfer to an appropriate conical measure with rinsings. 12 Measure 2. Point of clarity – Step 7 This is to wet the Acacia BP. . Point of clarity – Step 9 A characteristic clicking sound will be heard when the primary emulsion is formed. 7 Transfer the Acacia BP to the mortar and stir gently (approximately three stirs). 4 Accurately measure 60 mL Arachis Oil BP in a conical measure. 15 Stir and transfer to an amber flat medicine bottle. See Emulsions video for a demonstration of the preparation of an emulsion. freshly boiled and cooled purified water is used here as emulsions are susceptible to microbial contamination.3 Continued Point of clarity – Step 13 The Concentrated Peppermint Emulsion BP is added just prior to making up to volume as it is a volatile ingredient. 14 Make up to volume with any remaining Double Strength Chloroform Water BP and freshly boiled and cooled purified water. Point of clarity – Step 14 Even though there is a preservative in the preparation.144 | Pharmaceutical forms and their preparation Example 8. label and dispense to the patient. . 4 The preparation of a magistral formulation of 200 mL of Liquid Paraffin BP 15% emulsion from a doctor's prescription Example label (assuming a 15 mL dose) (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Liquid paraffin 15% v/v emulsion 200 mL Product directions.75 g Double Strength Chloroform Water BP 7. Therefore.5 mL Freshly boiled and cooled purified water to 15 mL Patient name Date of dispensing Product formula: Master (100 mL) 200 mL Liquid Paraffin BP 15 mL 30 mL Acacia BP qs qs Double Strength Chloroform Water BP 50 mL 100 mL Freshly boiled and cooled purified water to 100 mL to 200 mL First it is necessary to calculate the quantity of emulsifying agent (Acacia BP) required to produce 200 mL of the emulsion. Shake the Bottle Do not use after (4 weeks) Each 15 mL contains: Liquid Paraffin BP 2. Emulsions | 145 Example 8. Liquid Paraffin BP is a mineral oil. Therefore the product formula for 200 mL of Liquid Paraffin BP 15% emulsion is: 200 mL Liquid Paraffin BP 30 mL Acacia BP 10 g Double Strength Chloroform Water BP 100 mL Freshly boiled and cooled purified water to 200 mL Interim formula for Double Strength Chloroform Water BP (see Chapter 2. the amount of freshly boiled and cooled purified water needed is 2 10 ¼ 20 mL. 3 parts ¼ 30 mL. therefore the primary emulsion ratio is: Oil : Water : Gum 3:2:1 Since 30 mL of Liquid Paraffin BP is required. page 32): Concentrated Chloroform Water BPC 1959 5 mL Freshly boiled and cooled purified water to 100 mL . The amount of Acacia BP required ¼ 10 g.25 mL Acacia BP 0. One part will therefore be 30 3 ¼ 10. 5 Transfer the Liquid Paraffin BP to a clean dry porcelain mortar. Point of clarity – Step b Although potable water would usually be used in the manufacture of Double Strength Chloroform Water BP. accurate measurement of the concentrated component.146 | Pharmaceutical forms and their preparation Example 8. 100 mL of Double Strength Chloroform Water BP is required. c Add the measured Concentrated Chloroform Water BPC 1959 to the water in the conical measure. the accurate preparation of the primary emulsion is crucial for the full emulsion to be satisfactorily produced. freshly boiled and cooled purified water is used here as emulsions are susceptible to microbial contamination. d Stir gently and then accurately make up to volume with freshly boiled and cooled purified water. 4 Accurately measure 30 mL Liquid Paraffin BP in a conical measure. sufficient water to enable dissolution of the concentrated chloroform component without reaching the final volume of the product). Primary emulsion: Liquid Paraffin BP 30 mL Double Strength Chloroform 20 mL Water BP Acacia BP 10 g 2 Weigh 10 g of Acacia BP on a Class II or electronic balance. Method of compounding for Double Strength Chloroform Water BP: a In this case. See Solutions video for a demonstration of the preparation of Double Strength Chloroform Water BP.e. To prepare 100 mL Double Strength Chloroform Water BP. e Visually check that no undissolved chloroform remains at the bottom of the measure. measure 5 mL of Concentrated Chloroform water BPC 1959 accurately using a 5 mL conical measure. sufficient to satisfy the formula requirements but also enabling simple. . Point of clarity – Step 5 Ensure the measure is well drained as the quantities to be used are critical in the formation of the primary emulsion. 3 Accurately measure 100 mL Double Strength Chloroform Water BP using a 100 mL measure.4 Continued Method: 1 Calculate the composition of a convenient quantity of Double Strength Chloroform Water BP. b Add approximately 90 mL of freshly boiled and cooled purified water to a 100 mL conical measure (i. Point of clarity – Method Remember. Point of clarity – Step 12 Even though there is a preservative in the preparation. Gentle stirring is required to ensure that there is no heat production that might denature the gum and prevent the formation of the emulsion. Remember. 13 Stir and transfer to an amber flat medicine bottle. Point of clarity – Step 7 This is to wet the acacia. 11 Transfer to an appropriate conical measure with rinsings. . 9 Stir vigorously with the pestle in ONE direction only until the primary emulsion is formed. 8 Add the 20 mL of Double Strength Chloroform Water BP to the mortar all in one go.4 Continued 6 Measure 20 mL of Double Strength Chloroform Water BP (from the 100 mL measured in Step 3). 10 Add more Double Strength Chloroform Water BP to the primary emulsion until the emulsion is pourable. label and dispense to the patient. 7 Transfer the Acacia BP to the mortar and stir gently (approximately three stirs). freshly boiled and cooled purified water is used here as emulsions are susceptible to microbial contamination. 12 Make up to volume with any remaining Double Strength Chloroform Water BP and freshly boiled and cooled purified water. the whiter the primary emulsion the better it is formed. Point of clarity – Step 10 The Double Strength Chloroform Water BP needs to be added drop by drop to the primary emulsion until it is pourable to ensure that the primary emulsion does not crack. See Emulsions video for a demonstration of the preparation of an emulsion. Emulsions | 147 Example 8. Point of clarity – Step 9 A characteristic clicking sound will be heard when the primary emulsion is formed. 5 Preparation of 100 mL of Liquid Paraffin Emulsion BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Liquid Paraffin Emulsion BP 100 mL Product directions. page 54). 3 Add the Methylcellulose 20 BP to the heated water. Point of clarity – Step 12 The amount of Sodium Saccharin BP cannot be accurately weighed therefore a trituration must be prepared. . 7 Measure 0. 11 Add this solution to the previously prepared methylcellulose mucilage and stir for 5 minutes. page 744): 1000 mL 100 mL Liquid Paraffin BP 500 mL 50 mL Vanillin BP 500 mg 50 mg Chloroform BP 2.25 mL Benzoic Acid Solution BP 20 mL 2 mL Methylcellulose 20 BP 20 g 2g Saccharin Sodium BP 50 mg 5 mg Freshly boiled and cooled purified water to 1000 mL to 100 mL Method: 1 Heat about 12 mL of freshly boiled and cooled purified water. 9 Mix the Chloroform BP and Benzoic Acid Solution BP together. Shake the Bottle Do not use after (4 weeks) Patient name Date of dispensing Product formula (British Pharmacopoeia 1988. 12 Prepare a sodium saccharin trituration and add sufficient (5 mL) to provide 5 mg of Sodium Saccharin BP to the mixture. It is therefore more soluble in organic solvents and so is added to the chloroform-containing mixture. 10 Dissolve the Vanillin BP in the benzoic acid and chloroform mixture.5 mL 0. 5 Add sufficient freshly boiled and cooled purified water in the form of ice to produce 35 mL and stir.25 mL of Chloroform BP.148 | Pharmaceutical forms and their preparation Example 8. Point of clarity – Step 10 Vanillin BP is only slightly soluble in water but freely soluble in alcohol and soluble in ether. 8 Weigh 50 mg Vanillin BP using a sensitive electronic balance (see Chapter 4. 2 Weigh 2 g Methylcellulose 20 BP on a Class II or electronic balance. 6 Measure 2 mL of Benzoic Acid Solution BP using a syringe. 4 Allow to stand for about 30 minutes to hydrate. Water is the diluent chosen as this is also the vehicle for the emulsion. 15 Mix the 50 mL mucilage and 50 mL of Liquid Paraffin BP together and stir constantly. When an emulsion is passed through a homogeniser (Figure 8. label and dispense. Emulsions | 149 Example 8.5 Continued Trituration for Sodium Saccharin: Saccharin Sodium BP 150 mg Freshly boiled and cooled purified water to 150 mL Therefore 5 mL of the trituration will contain 5 mg of Sodium Saccharin BP. Although many extemporaneously prepared emulsions do not require the use of a homogeniser. 13 Make the volume of the mucilage mixture up to 50 mL with freshly boiled and cooled purified water. 16 Pass through a homogeniser to make the emulsion more stable. Figure 8. 17 Transfer to an amber flat medicine bottle with a child-resistant closure. this step may aid in retarding or preventing creaming of the emulsion on long standing. Point of clarity – Step 16 The stability of an emulsion is increased with smaller globule size of the disperse phase.2 A homogeniser. 14 Measure 50 mL of Liquid Paraffin BP in a 50 mL conical measure.2) the emulsion is forced through a fine opening to apply shearing forces to reduce the size of the globules. . 5 g Freshly boiled and cooled purified water 625 mL 62. 6 Add to the oily phase and mix vigorously.5 mL 9 mL Ammonium Chloride BP 12.5 mL 17 mL Turpentine Oil BP 250 mL 25 mL 50 mL Dilute Ammonia Solution BP 45 mL 4. combined with the relatively large volume of turpentine oil in the product. suppresses the ionisation of the soap by the common ion effect and this. 5 Add an equal volume of warm freshly boiled and cooled purified water to the Dilute Ammonia Solution BP. Shake the Bottle For External Use Only Do not use after (4 weeks) Patient name Date of dispensing Product formula (British Pharmacopoeia 1988. 9 Add the solution in Step 8 to the emulsion and mix. The ammonium chloride. 2 Measure 50 mL Turpentine Oil BP. page 700): 1000 mL 100 mL 200 mL Oleic Acid BP 85 mL 8. 8 Add the Ammonium Chloride BP to the remaining freshly boiled and cooled purified water in a beaker and stir to dissolve.25 g 2. The interaction between the fatty acid (oleic acid) and ammonia produces ammonium oleate. however. Point of clarity – Method This is an ammonium soap type of emulsion.150 | Pharmaceutical forms and their preparation Example 8. 10 Measure 200 mL of the emulsion and transfer to an amber fluted medicine bottle.5 g of Ammonium Chloride BP on a Class II or electronic balance. 7 Weigh 2. causes phase inversion and a water-in- oil emulsion is formed. 4 Measure 9 mL Dilute Ammonia Solution BP and transfer to a beaker.5 g 1. an oil-in-water emulgent. 3 Mix together the Turpentine Oil BP and Oleic Acid BP in a mortar. .6 Preparation of 200 mL of White Liniment BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): White Liniment BP 200 mL Product directions.5 mL 125 mL Method: 1 Measure 17 mL Oleic Acid BP. As with solutions and suspensions. a suitable container would be a flat amber stored for a period greater than four weeks when medical bottle. 100 mL. An overview of the texts. this sec- if available) 300 mL and 500 mL tion contains: External Amber fluted medical 50 mL. page 111). compounded items that are likely to deteriorate if nal use. Emulsions | 151 Summary of essential principles Table 8. they are liable to ent sizes and it is important to choose a suitably sized microbial contamination. 100 mL. Discard dates Discard dates for pharmaceutical emulsions typi- cally mirror those for pharmaceutical solutions (see Labelling Chapter 6. 200 mL extemporaneously prepared emulsions (applications mouthed if available) * specific points relevant to the expiry of and lotions) extemporaneously prepared emulsions * additional key points related to the labelling of pharmaceutical emulsions. creams. extemporaneous preparation of emulsions. The discard date of official prep. Consideration should be given to selecting a ferred method of indicating shelf-life on the label of bottle that will leave sufficient space to allow the prod- extemporaneously compounded products is to apply uct to be shaken adequately before a dose is measured.5. are useful when extemporaneously compounding Packaging emulsions: The packaging of extemporaneous preparations has * ‘Freshly Prepared’ refers to a preparation that has been covered previously in Chapter 5 (page 97). Obviously it is important not to use a size of to 7–14 days. External emulsions (e. * ‘Recently Prepared’ should be applied to With pharmaceutical emulsions intended for inter. prepared emulsions are summarised in Table 8. consider- container to match the volume of preparation to be ation should be given to shortening the expiry date dispensed. ments. page 160). lotions. . An been compounded less than 24 hours prior to issue overview of the main considerations for the packaging for use. 200 mL. * further notes on the packaging of emulsions bottle (wide. For this reason. Although emulsions (see Chapter 9.5 Summary of packaging for relating to emulsions pharmaceutical emulsions This section will recap the main principles relating to Typical sizes emulsions that have been covered in other sections of the book. The labelling of pharmaceutical emulsions has been arations will be advised via the relative official covered in Chapter 5 (page 92). maintained at 15–25 C. for both cost and appearance derstand the term ‘expiry’ it is suggested that a pre- reasons. for official main considerations for the labelling of emulsions will preparations the BP employs two definitions that be given here. etc. To assist compounders in understanding the Oral Amber flat medical 50 mL.) would be packaged in suitable Traditionally it was suggested that an expiry date containers. usually contain a preservative (Double Strength Pharmaceutical bottles come in a variety of differ- Chloroform Water BP at 50% v/v). lini. container that is too large for the volume of prepara- Remember that because patients frequently misun- tion to be dispensed. the term ‘Discard after’ or ‘Do not use after’ followed Guidelines on the packaging of extemporaneously by a definite date and/or time.g. emulsions bottle (wide-mouthed 150 mL. for example a fluted amber bottle for lini- of four weeks be applied to oral emulsions in the ments and lotions and a collapsible tube for a cream absence of any official guidance. of emulsions will be given here. Further guidance on expiry dates for pharmaceu- tical preparations can be found in Chapter 5 (page 93). the follow. Table 5. * ‘Shake the bottle’ – All emulsions will require this Further guidance on auxiliary labelling can be additional label. found in Chapter 5. be added to the label of any external ing points need to be taken into consideration: emulsion.152 | Pharmaceutical forms and their preparation In addition to the standard requirements for the * ‘For external use only’ – This warning must labelling of extemporaneous preparations.10. . 9 Creams Introduction and overview 153 Incorporation of ingredients into a cream base 155 Terminology used in the preparation of creams. white or translucent and rather stiff.g. beeswax. . ointments. therapeutic or prophylactic purposes depending on the emulsifying agent used. They preparation of creams. ointments. wool alcohols or wool fat). necessary. They are intended to be applied to the suspended in creams. * Water-in-oil creams (oily creams) as bases – These are produced by the emulsifying agents of natural origin (e. Medicaments can be dissolved or secretion. A cream is especially where an occlusive effect is not always miscible with its continuous phase. pastes and gels * Oil-in-water creams (aqueous creams) as bases – These are produced by the synthetic waxes (e. pastes and gels (see of drugs.g. (¼ grinding). Terminology used in the These bases have good emollient properties. They are thin. skin or certain mucous membranes for pro- A cream may be ‘water-in-oil’ or ‘oil-in-water’ tective. are creamy. pastes and gels 153 Worked examples 156 Trituration 154 Summary of essential principles relating to creams 160 Levigation 154 Packaging 160 Methods for incorporating solids and liquids into cream and ointment bases 154 Discard dates 160 General principles of cream preparation 154 Labelling 161 The preparation of a cream from first principles 154 Introduction and overview The British Pharmacopoeia (BP) definition is as follows: In pharmacy the term ‘cream’ is reserved for external Creams are formulated to provide prepara- preparations. They are the best preparation of creams and in the extemporaneous bases to use for rapid absorption and penetration preparation of ointments. Two common terms used in the extemporaneous macrogol and cetomacrogol). white and smooth in Chapter 10) are trituration (¼ mixing) and levigation consistency. Creams are viscous semi-solid emulsions tions that are essentially miscible with the skin for external use. * Melt the fatty bases in an evaporating dish over a Levigation water bath at the lowest possible temperature. solid base. This is the term applied to the incorporation into the Start with the base having the highest melting base of insoluble coarse powders. transfer the entire cream into the final container. pockets that contain liquid. – for a water-in-oil (w/o) product add water to oil.1 Summary of the methods for incorporating solids and liquids into cream and ointment bases Medicament Molten base Solid base Soluble powder Fusion – dissolve in base at the lowest Trituration temperature possible Insoluble coarse powder Levigation Levigation with a small amount of solid base Insoluble fine powder Incorporate in small amounts. will spray fluid purified water as it will quickly evaporate. Small quantities of liquid are then added and and other equipment must be thoroughly mixed in. * Determine which of the ingredients are soluble in/ Trituration can be successfully achieved using a mor- miscible with the aqueous phase and which with tar but this method is usually reserved for large the oily phase. Trituration as the base cools and thickens Volatile liquid Incorporate when the ointment has cooled Trituration to below 40 C by trituration Non-volatile liquid Incorporate into molten base by trituration Trituration . Hence. into the preparation base. Dissolve the water-soluble quantities. by trituration. Table 9. hygiene is amount of base on a tile and making a ‘well’ in the extremely important and all surfaces. and the stability of the product can be lost). These should then be cooled to 60 C ‘wet grinding’. * The temperature of the aqueous phase should then Methods for incorporating solids and be adjusted to 60 C. incorporating solids and liquids into cream or oint. It is often termed point. leaving no residue. – for an oil-in-water (o/w) product add oil to water ment bases. which if squeezed when IMS is better than freshly boiled and cooled using an inappropriate mixing action. spatulas centre. A considerable shearing force is applied to * Substances that are soluble/miscible with the oily avoid a gritty product.154 | Pharmaceutical forms and their preparation Trituration General principles of cream This is the term applied to the incorporation. on the compounder and surrounding area. It is important to take care not to form air cleaned with industrial methylated spirits (IMS).1 gives a summary of the methods used for continuous phase at the same temperature. liquids into cream and ointment bases * The disperse phase should then be added to the Table 9. principles Liquids are usually incorporated by placing a small * As with other types of emulsion. See Ointments video for a demonstration of * Always make an excess as it is never possible to trituration. The powders are placed on the tile and the base is The preparation of a cream from first incorporated using the ‘doubling-up’ technique. ingredients in the aqueous phase. of finely divided insoluble powders or liquids. It is the process where the powder is (overheating can denature the emulsifying agent rubbed down with either the molten base or a semi. phase should then be stirred into the melt. A evaporation. sol. Alternatively. the solid can be incorporated into the cream as it * Non-volatile. until the product sets. then the method employed for insoluble solids. small quantities powder to be added these should be triturated of liquid should be gently folded in to avoid together in a mortar using the ‘doubling-up’ splashing. An alternative method is to spread a technique prior to transfer to an ointment tile. These should be well triturated. Then add small quantities See Powders video for a demonstration of of the liquid and fold into the base gently.g. the molten cream in the evaporating basin. In addition to the preparation of a cream from first See Ointments video for a demonstration principles. * Volatile or immiscible liquids (e. Incorporation of liquids into a cream base ples. miscible liquids may be mixed with cools. The powder/ of the incorporation of a liquid into a base. A very small amount of the * Insoluble solids should be incorporated using an cream should be placed on the tile and a ‘well’ ointment tile and spatula. the ointment tile. fatty base mixture may then either be returned . if using a pre-prepared base. small amount of the cream on the tile and then ‘score’ it with a spatula. these should not be weighed until immediately before use and – For coarse powders a minimum quantity of the beaker in which it has been weighed should be cream should be placed in the centre of the tile covered with a watch glass to prevent and used to levigate the powders. Creams | 155 * Stir the resulting emulsion without incorporating – to the evaporating basin with the remaining air. using the ‘doubling- into a cream base up’ technique). preparation of a cream from first principles. base. If there is more than one made in the centre. incorporate as for volatile or immiscible liquids. Traditionally. If using the ‘doubling-up’ technique. Incorporation of solids into a cream base If the cream base has been prepared from first princi. Small amounts of powder should be added to an Incorporation of ingredients equal amount of cream (i. uble and insoluble solids may be incorporated using Alternatively. it is common to incorporate either liquid or of the incorporation of a powder into a solid ingredients into a cream base. Do not hasten cooling cream and stirred until cold or the remaining as this produces a poor product.e. if a pre-prepared base is used. coal tar or other volatile ingredients. considerable lateral shearing force should be See Ointments video for a demonstration applied to avoid a gritty product. cream in the evaporating basin may be allowed to cool and triturated with the powder/cream See Creams video for a demonstration of the mixture on the tile. coal tar * Soluble solids should be added to the molten cream at the lowest possible temperature and the solutions) should be triturated with the cream on mixture stirred until cold. – Fine powders may be triturated into the otherwise finished cream on an ointment tile. Therefore. When melted.35 g Point of clarity – Product formula The exact quantity cannot be prepared for a cream as losses will be encountered on transfer.1 Preparation of 20 g Cetrimide Cream BP Example label: we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Cetrimide Cream BP 20 g Product directions. 5 Melt the Cetostearyl Alcohol BP in an evaporating basin over a water bath to a temperature no higher than 60 C.156 | Pharmaceutical forms and their preparation Worked examples Example 9. 3 Weigh 13. . For External Use Only Do not use after (4 weeks) Patient name Date of dispensing Product formula (British Pharmacopoeia 1988.5 g 4.5 g Cetostearyl Alcohol BP on a Class II or electronic balance. 2 Weigh 15 g of Liquid Paraffin BP on a Class II or electronic balance.5 g Liquid Paraffin BP 500 g 50 g 5g 15 g Freshly boiled and cooled purified water 445 g 44. a suitable overage must be produced in order to dispense the required final amount. Slightly soluble in alcohol. 4 Weigh 150 mg of Cetrimide BP on a Class II or electronic balance. miscible with liquid paraffin Cetrimide BP Soluble in 2 parts water Liquid Paraffin BP Practically insoluble in water.45 g 13. Melting points and solubilities of the ingredients: Melting point: Cetostearyl Alcohol BP 49–56 C Solubilities: Cetostearyl Alcohol BP Practically insoluble in water.35 g of freshly boiled and cooled purified water on a Class II or electronic balance. page 653): 1000 g 100 g 10 g 30 g Cetrimide BP 5g 500 mg 50 mg 150 mg Cetostearyl Alcohol BP 50 g 5g 500 mg 1. 7 Stir to form the OILY phase. Miscible with hydrocarbons Method to prepare 30 g of Cetrimide Cream BP from the formula above: 1 Weigh 1. Note that all liquid ingredients (including the Liquid Paraffin BP) must be weighed. 8 Transfer the freshly boiled and cooled purified water to a beaker and heat to 60 C. 6 Add the Liquid Paraffin BP to the molten Cetostearyl Alcohol BP and remove from the heat. 13 Weigh 20 g of the product and pack into an amber glass jar. 11 When the oily phase and the aqueous phase are both at about 60 C. . label and dispense.1 Continued 9 Add the Cetrimide BP to the freshly boiled and cooled purified water and remove from the heat. 12 Stir until cool enough to pack. See Creams video for a demonstration of the preparation of a cream from first principles. Creams | 157 Example 9. not too vigorous stirring. 10 Stir to form the AQUEOUS phase. Point of clarity – Step 11 Stirring is constant and not too vigorous to ensure that there are no ‘cold spots’ within the cream as these would hasten cooling in discrete areas and result in a lumpy cream. add the aqueous phase to the oily phase with constant. 4 Add to the Salicylic Acid BP in the glass mortar and continue mixing with a pestle until a smooth.8 g Method to prepare 30 g of Salicylic Acid and Sulphur Cream BP from the formula above: 1 Weigh 600 mg Salicylic Acid BP on a Class II or electronic balance. Label and dispense. 7 Transfer the Aqueous Cream BP to the glass tile and triturate with the powders to produce a smooth product. etc.158 | Pharmaceutical forms and their preparation Example 9.6 g 28. 5 Transfer the powder to a glass tile. For External Use Only Do not use after (4 weeks) Patient name Date of dispensing Product formula (British Pharmacopoeia 1980.2 Preparation of 20 g of Salicylic Acid and Sulphur Cream BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Salicylic Acid and Sulphur Cream BP 20 g Product directions. 2 Transfer to a glass mortar and grind with a pestle. . Vulcanite (also called ebonite) is a hard. tannins. iodine and mercury salts. 3 Weigh 600 mg Precipitated Sulphur BP on a Class II or electronic balance. 6 Weigh 28. produced by vulcanising natural rubber with sulphur. 8 Weigh 20 g of the product and pack into an amber glass jar. Point of clarity – Step 7 Note: a vulcanite spatula would be the spatula of choice as traditional stainless steel spatulas may react with acids. usually black. rubber. Such spatulas are used for making ointments containing corrosive substances or substances that react with steel. well mixed powder is formed. page 548): 1000 g 100 g 10 g 30 g Salicylic Acid BP 20 g 2g 200 mg 600 mg Precipitated Sulphur BP 20 g 2g 200 mg 600 mg Aqueous Cream BP 960 g 96 g 9.8 g Aqueous Cream BP on a Class II or electronic balance. 5 g 15 g Cetomacrogol Cream (Formula A) BPC 75% 75 g 7. Creams | 159 Example 9. For External Use Only Do not use after (2 weeks) The product contains: Dermovate Cream 25% Cetomacrogol Cream (Formula A) BPC 75% Patient name Date of dispensing Product formula (i.e. . * Cetomacrogol Cream (Formula A) BPC – No problems with dilution recorded. 3 Weigh 45 g Cetomacrogol Cream (Formula A) BPC on a Class II or electronic balance. which in this case states that although the dilution of the product is not recommended by the manufac- turer. 4 Transfer to the glass tile. the diluent to use) must be decided by the compounder. Refer to a diluent directory. Therefore unsuitable for this formulation. Point of clarity – sources of information Suitable sources to provide information on the dilution of creams and ointments would be: * NPA Diluent Directory * Product data sheet (Summary of Product Characteristics – SPC) * Reports in the pharmaceutical literature * Personal contact with product manufacturer. * Buffered Cream BP – May be used but can raise the pH of the resulting cream.3 Preparation of 50 g of Dermovate Cream 25% Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Dermovate Cream 25% w/w 50 g Product directions. 5 Triturate the Dermovate Cream with the Cetomacrogol Cream (Formula A) BPC using a spatula.5 g 45 g Method to prepare 60 g of Dermovate Cream 25% from the formula above: 1 Weigh 15 g Dermovate Cream on Class II or electronic balance. Product formula: Master formula 100 g 10 g 60 g Dermovate Cream 25% 25 g 2. the following may be used: * Aqueous Cream BP – Only stable if less than 50% of the resultant cream. 2 Transfer to a glass tile. in cases where it is insisted upon. Therefore in this instance the diluent of choice would be Cetomacrogol Cream (Formula A) BPC. 100 g of ointment will not fit in a 100 g ointment jar. More recently. plastic ointment jars have book. label and dispense to the patient. page 181). 7 Pack into an amber glass jar. be dispensed. Obviously it is Diluted creams (see Example 9. are less preferable because of an increased likeli- contains: hood of the products reacting with the container (e. Do not be fooled by the stand the term ‘expiry’ it is suggested that a preferred size marked on the bottom of the jar: the value refers to method of indicating shelf-life on the label of . * specific points relevant to the expiry of ensure that the cream is packed well and that no air extemporaneously prepared creams pockets are visible.3 Continued Point of clarity – Step 5 When triturating the creams together remember the principle of ‘doubling-up’ in order to achieve an adequate mix of the active Dermovate Cream and the base cream. it is suggested that creams are be either an amber wide-necked ointment jar or a given a four-week discard date. shorter than the suggested discard date for extempo- Pharmaceutical ointment jars come in a variety of raneously prepared ointments (which is three months) different sizes and it is important to choose a suitably because of the susceptibility of creams to microbial sized container to match the volume of preparation to contamination (see Chapter 10. Packaging The packaging of extemporaneous preparations has been covered in Chapter 5 (page 97). This is significantly metal collapsible tube. pharmaceutical creams. An overview of Discard dates the main considerations for the packaging of creams Some official texts may give a suggested discard date will be given here.160 | Pharmaceutical forms and their preparation Example 9. As relating to creams ointments are less dense than water. extemporaneously prepared creams When packaging a cream into an ointment jar.g. 6 Weigh 50 g of the final cream on a Class II or electronic balance. * further notes on the packaging of as can occur with preparations containing coal tar). a suitable container would absence of any guide. this section jars. Amber glass jars are preferable to clear glass jars as This section will recap the main principles relating to they protect the preparation from degradation by creams that have been covered in other sections of the light.3) would normally important not to use a size of container that is too large be given a two-week discard date. for both Remember that as patients frequently misunder- cost and appearance reasons. This will produce a product with a * additional key points relating to the labelling of professional appearance. In the intended for external use. To assist compounders in understanding the become available and. This is best done by eye. See Creams video for a demonstration of the packaging of a cream. As all pharmaceutical creams are for certain extemporaneously prepared creams. for the volume of preparation to be dispensed. Summary of essential principles the weight of water that the container will hold. although cheaper than glass extemporaneous preparation of creams. An overview of the main Further guidance on auxiliary labelling can be considerations for the labelling of creams will be given found in Chapter 5. added to the label of all extemporaneously prepared creams as all creams are for external use Labelling only. Table 5. . Creams | 161 extemporaneously compounded products is to apply In addition to the standard requirements for the the term ‘Discard after’ or ‘Do not use after’ followed labelling of extemporaneous preparations. here. The labelling of pharmaceutical creams has been cov- ered in Chapter 5 (page 92). ing points need to be taken into consideration: Further guidance on expiry dates for pharmaceu- * ‘For external use only’ – This warning must be tical preparations can be found in Chapter 5 (page 93).10. the follow- by a definite date and/or time. . preparation smoother and lighter in consistency. The base is usually anhydrous and immiscible with * waxes – solid and hard at room temperature skin secretions. pro.g. The proportions used may . fat and wax in the ments are intended to be applied to the skin or ointment may vary the consistency. Hydro. pastes and gels 181 General method for ointment preparation 164 Packaging 181 Pastes 165 Discard dates 181 Gels 167 Labelling 181 Gelling agents 167 Other additives for gels 169 Introduction and overview where a degree of occlusion is desired. Ointments usually contain a medica. arations that are immiscible. * oils – liquid at room temperature. pastes and gels Introduction and overview 163 General method of manufacture for gels 169 Ointments 163 Worked examples 170 Ointment bases 163 Summary of essential principles relating to ointments. fats and oils: but differ from creams in that they have greasy bases. extra certain mucous membranes for emollient. For example. A change in temperature can affect the physical According to the British Pharmacopoeia (BP): state of a base (e. Ointments Ointment bases The base of a traditional ointment consists of a mix- Ointments are preparations for external application ture of waxes. persed in the base. * fats – semi-solid. is more likely to be liquid in summer). soft at room temperature ment or a mixture of medicaments dissolved or dis. wax will make the ointment stiffer. extra oil will make tective. coconut oil is solid in winter but Ointments are formulated to provide prep.10 Ointments. miscible or The addition of a wax to an ointment makes the emulsifiable with the skin secretion. Altering the proportions of oil. pastes and gels. Hydrophilic ointments are miscible with the This chapter will focus on three common dosage skin secretion and are less emollient as a forms: ointments. therapeutic or prophylactic purposes the ointment less viscous. consequence. phobic ointments and water-emulsifying oint. 2 Determine the melting points of the fatty bases and then melt together. monly used with local anaesthetics such as Lidocaine proof film on the skin. The consist of a hydrocarbon base combined with a ointment base may include a mixture of waxes. Absorption bases can be methods for incorporating solids and liquids into divided into non-emulsified bases and water-in-oil cream or ointment bases can be found in Table 9. water and therefore washable and easily removed after 3 Add the ingredients to an evaporating basin over use. The paraffins form a greasy water.g. each base should These are anhydrous bases that contain oil-in-water be melted at the lowest possible temperature as emulsifying agents. It is .g. are particularly suitable for use on the scalp (see Different types of ointment bases are available (see also Chapter 5. and others are liquid: Emulsifying agent Ointment * Hard – Paraffin BP. whether the product is intended for use in the tions of the skin and therefore wash out easily. which is particularly important in the treatment of dry General method for ointment preparation scaly conditions (see also Chapter 5. An explanation Absorption bases are good emollients and are less of the terminology used in ointment preparation can occlusive and easier to apply than hydrocarbon bases be found in Chapter 9 (page 153) and a summary of the (see also Chapter 5. fats water-in-oil emulsifier such as Wool Alcohols BP and oils. stirring continuously to ensure a (non-ionic). Hydrophilic bases Hydrocarbon bases These have been developed from polyethylene glycols These bases are immiscible with water and are not (macrogols). * Water-in-oil emulsions – These are similar to non- emulsified bases but are capable of absorbing Method (fusion) more water. Wool Wool Fat BP Simple Ointment BP Fat BP * Liquid – Liquid Paraffin BP and vegetable oils. This inhibits water loss from BP (see also Chapter 5. emulsions: Fusion * Non-emulsified – These bases absorb water to This involves melting together the bases over a water form water-in-oil emulsions. They are non-occlusive. thereby improving the hydration of the skin. * Emulsifying Ointment BP (anionic) 4 As the first base cools add the ingredients with * Cetrimide Emulsifying Ointment BP (cationic) decreasing melting points at the respective * Cetomacrogol Emulsifying Ointment BPC temperatures. below and also Chapter 5. Generally they bath before incorporating any other in gredients. the skin. Macrogol bases are com- liquid paraffin. page 79). they Tropics or in the Arctic). Cream BP (Hydrous Ointment BP). affin or mixtures of soft paraffin with hard paraffin or Macrogol Ointment BP). Beeswax BP. skin secretions and are easily removed by washing (e. page 79). The following three emulsifying ointments are a water bath to avoid overheating – use a used as water-miscible bases: thermometer to check the temperature regularly. homogeneous mix before leaving to set. They usually consist of soft par. Cetostearyl Wool Alcohols BP Wool Alcohols Ointment BP Alcohol BP * Soft – Yellow and White Soft Paraffin BP. This section contains information on the preparation of ointments by fusion and the incorporation of both Absorption bases solids and liquids into ointment bases.1. which make them miscible with the mixture progressively cools. of which some are solid at room temperature or Wool Fat BP. The constituents of emulsified bases 1 Always make excess as transference losses will include Hydrous Wool Fat BP (lanolin) and Oily always occur. page 78).164 | Pharmaceutical forms and their preparation vary depending on storage or the climatic conditions As the bases mix readily with the aqueous secre- (e. Starting with the base Water-miscible/emulsifying bases with the highest melting point. page 79). mix readily with absorbed by the skin. page 78). and Alternatively. These should be well triturated to salicylic acid. . such as dithranol. Then add small quantities Insoluble solids should be incorporated using an oint. if a pre-prepared base is used. if using a pre- Traditionally. A very small amount of the ointment should be bases at the lowest possible temperature and the mix- placed on the tile and a ‘well’ made in the centre.g. Alternatively. The powder/fatty base mixture may then Pastes are semi-solid preparations for external use. or bined with White Soft Paraffin BP or Liquid Paraffin the remaining fatty base in the evaporating basin BP or with a non-greasy base made from glycerol. soluble solids may be incorporated folded in to avoid splashing. of powdered ingredients and therefore are normally * Fine powders may be triturated into the otherwise very stiff.e. to be added these should be mixed in a mortar using these should not be weighed until immediately before the ‘doubling-up’ method. coal tar or technique). either be returned to the evaporating basin with They consist of finely powdered medicaments com- the remaining fatty base and stirred until cold. coal tar solutions) Soluble solids should be triturated with the ointment on the ointment Soluble solids should be added to the molten fatty tile. tile and the resulting mixture returned to the Pastes are also useful for absorbing harmful remaining molten mass and stirred to achieve a chemicals. evaporation. Ointments. pastes and gels | 165 important to stir gently to avoid incorporating General method for incorporating liquids into excess air. and so are often used in See Ointments video for a demonstration of the nappy products. Also because of their high powder incorporation of a powder into a base. ture stirred until cold. which could result in localised cooling an ointment base and a lumpy product. Because pastes are stiff they do not spread finished ointment on an ointment tile. miscible liquids may be mixed with the fusion method. miscible liquids See Ointments video for a demonstration of the Non-volatile. then incorporate as for vol- atile or immiscible liquids. small quantities of liquid should be gently prepared base. An alternative method is to using the method employed for insoluble solids. molten fat in the evaporating basin. Alternatively. skin area such as a particular lesion or plaque. See Ointments video for a demonstration of the * Coarse powders – A minimum quantity of molten incorporation of a liquid into an ointment. spread a small amount of the ointment on the tile and Insoluble solids then ‘score’ it with a spatula. may be allowed to cool and triturated with the mucilages or soaps. ment tile and spatula. a small amount of powder may be thereby not compromising the integrity of healthy levigated with some molten ointment base on a skin. of the liquid and fold into the base gently. Pastes contain a high proportion powder/fatty base mixture on the tile. Non-volatile. use and the beaker in which it has been weighed See Powders video for a demonstration of the should be covered with a watch glass to prevent ‘doubling-up’ technique. using the ‘doubling-up’ the skin is corrosive. This is amounts of powder should be added to an equal particularly important if the ingredient to be applied to amount of ointment (i. A considerable Pastes shearing force should be applied to avoid a gritty product. It is easier to apply a paste to a discrete incorporate all of the ointment base. Small easily and therefore this localises drug delivery. bacterial action on urine. such as the ammonia that is released by homogeneous product. content. fatty base should be placed in the centre of the tile and used to levigate the powders. General method for incorporating powders into an ointment base Volatile or immiscible liquids Volatile or immiscible liquids (e. they are often used to absorb wound exudates. If there is more than one powder If using coal tar or other volatile ingredients. Formula: 2 Mix well and stir until just setting. The method outlined is designed to reduce technique. The principal use of pastes traditionally was as an Formula: antiseptic. Liquid Paraffin BP 400 g 4 Levigate the semi-molten base with the Method: powders on a warmed tile. Often before application the paste was applied to lint and Zinc Oxide BP (finely sifted) 60 g Coal Tar BP 60 g applied as a dressing. protective or soothing dressing. 1 Sieve the Aluminium Powder BP and the The emulsifying wax is added to help with Zinc Oxide BP. page 767) 1 Melt the Yellow Soft Paraffin BP and Emulsifying Wax BP at the lowest possible temperature. the dispersal of the coal tar through the prod- 2 Mix the powders using the ‘doubling-up’ uct. This is used as an antipruritic preparation. Emulsifying Wax BP 50 g Starch BP 380 g Yellow Soft Paraffin BP 450 g Example 10. This was what was originally used to pro- tect the skin and prevent maceration around colostomies and ileostomies. Aluminium Powder BP 200 g 3 Mix the powders using the ‘doubling-up’ Zinc Oxide BP 400 g technique.2 Zinc and Coal Tar Paste can act as a sun filter. page 868) the skin (wind burn) in addition to sun blocking. the amount of heat to which the coal tar is 3 Mix the combined powders with the exposed as the constituents of coal tar tend to Liquid Paraffin BP. 5 Finally incorporate the Coal Tar BP.166 | Pharmaceutical forms and their preparation Because pastes are so thick they can form an unbroken layer over the skin which is opaque and Example 10. . stirring until a smooth precipitate out quickly on heating. product is formed. This makes them suitable for BP (also known as White's Tar Paste) use by skiers as they prevent excessive dehydration of (BP 1988.1 Compound Aluminium Method: Paste BPC (also known as Baltimore Paste) (BPC 1973. quite freely provided the medicament does not bind 10 Pour into a shallow tray and allow to set. rapid absorption. Common 9 Continue stirring until the preparation is gelling agents used in aqueous gels are discussed viscous enough to support the powder below. By cutting water and therefore most formulae will the paste into cubes this reduces the tendency include a wetting agent such as ethanol. with the polymer or clay used in its formation. the gelling agent used in their preparation. The Formula: liquid phase of the gel may be retained within a three- dimensional polymer matrix. 3 Stir gently until dissolved. pastes and gels | 167 Gels Example 10. The gel reforms on cooling and the produce different viscosities. and should lumps develop they will disperse easily on standing. 7 Adjust the base to weight by evaporation or adding hot water as required. product should be minimised. Gelatin BP 150 g The advantages of gels are that: Glycerol BP 350 g Water 350 g (or sufficient quantity) * they are stable over long periods of time * they have a good appearance Method: * they are suitable vehicles for applying 1 Heat the water to boiling. 6 Maintain the base at 100 C for 1 hour to eczema * lubricant gels remove any contaminant * spermicidal gels. This is usually cut up into cubes which are weighed out and dispensed. transpar- page 1097) ent semi-solid systems that are being increasingly used as pharmaceutical topical formulations. Re-melting is achieved by standing the con. liable to microbial contamination.3 Zinc Gelatin BPC (also known as Unna's Paste) (BPC 1968. By pre-wetting dispensed in portions of appropriate size the tragacanth. zinc oxide acts as an absorbent and mild * Tragacanth is a natural product and is therefore astringent. Tragacanth The preparation is designed to be re-melted before application as a dressing for varicose * Concentrations of 2–5% of tragacanth are used to ulcers. Generally the medication in a gel is released but is still pourable. Drugs can be suspended Zinc Oxide BP (finely sifted) 150 g in the matrix or dissolved in the liquid phase. . * anaesthetic gels 5 Stir gently to prevent incorporation of * coal tar gels for use in treatment of psoriasis or air bubbles until solution is complete. * The gum tends to form lumps when added to tainer of Unna’s Paste in hot water. 2 Remove from the heat and add the giving high rates of release of the medicament and gelatin. of the zinc oxide to sediment out. Gels are usually translucent or transparent and 4 Add the glycerol which has previously have a number of uses: been heated to 100 C (no higher). Gelling agents 8 Sift the Zinc Oxide BP and add in small The consistency of gels can vary widely depending on amounts of molten base. Usually this is glycerol or propylene glycol. microorganisms. medicaments to skin and mucous membranes. the problems of a lumpy intended for single use by the patient or nurse. Ointments. Pharmaceutical gels are often simple-phase. glycerol.168 | Pharmaceutical forms and their preparation Example 10. Cellulose derivatives * Cellulose derivatives are widely used and form Alginates neutral. carboxymethylcellulose) is used in concentrations * Wetting agents (such as glycerol) need to be of 1. * Alginate concentrations of 1. * It is prone to water loss and therefore necessitates * Carbomer is useful in production of clear gels the addition of a humectant (e. . preservative) in a mortar. 4 Stir to form a smooth-flowing liquid. of Glycerol BP in a beaker.5 A typical alginate gel gel formula formula Formula: Formula: Sodium Alginate BP 7% w/w Tragacanth BP 3% w/w Glycerol BP 20% w/w Glycerol BP 7% w/w Alcohol BP 2. * Methylcellulose 450 is used in strengths of 3–5% * Alginate concentrations of 5–10% produce to produce gels. any powdered ingredi.5–5% to make lubricating gels. dried on the skin. (not too rapidly to avoid incorporation of 5 Add any remaining glycerol. * They exhibit good resistance to microbial attack. gel production).5% produce fluid gels. In higher employed to prevent production of a lumpy product. to wetting. stable gels. dermatological grade gels suitable for topical * Carmellose sodium (sodium application. * The viscosity of alginate gels is more standardised * They form clear gels with good film strength when than that of tragacanth.2% w/w Methylparahydroxybenzoate BP 0. 6 Add all the water in one addition and stir (not too rapidly to avoid incorporation of air bubbles). 2 Place the Glycerol BP in a beaker.2% w/w Water to 100% Water to 100% Method: Method: 1 Mix together the Sodium Alginate BP and 1 Mix together the Tragacanth BP and the the Methylparahydroxybenzoate BP (the Methylparahydroxybenzoate BP (the preservative) in a mortar. 2 Place the Alcohol BP and a small amount 3 Add the powder slowly. air bubbles). such as the crystalline Gelatin is rarely used as the sole gelling agent in der- Methylparahydroxybenzoate BP. * Pectin is suitable for acid products.4 A typical tragacanth Example 10. As a general rule. 5 Add all the water in one addition and stir 4 Stir to form a smooth-flowing liquid. concentrations it is used to make dermatological Pectin gels. 3 Add the powder slowly.g. Carbomer * It is prone to microbial contamination. Gelatin ents to be added to a gel. should be matological preparations. (provided too much air is not incorporated in the propylene glycol or sorbitol). It is usually combined with admixed with the Tragacanth BP powder prior other ingredients such as pectin or carmellose sodium.5% w/w Methylparahydroxybenzoate BP 0. exception of water) to approximately 90 C. the gel leaves a powdery residue on the 1 Heat all components of the gel (with the skin. Ointments. * Differing viscosities are achieved depending on Preservatives the concentration of polyvinyl alcohol used Gels have a higher water content than either (normally 10–20%) and the grade of polyvinyl ointments or pastes and this makes them susceptible alcohol employed. The * Carbomer is used in dermatological preparations addition of a humectant can minimise this.001%) Methylcellulose .3–1%. * glycerol in concentrations of up to 30% drying gels.02%) Polyvinyl alcohols Chlorocresol (0. to microbial contamination.2%) Alginates Pectin (provided the product is acidic in nature) Methyl/propyl hydroxybenzoates (0. * propylene glycol in concentrations of * It leaves a residual film that is strong and plastic.5–5%. Other additives for gels include humectants and Avoid vigorous stirring as this will introduce preservatives. Choice of preserva- tive is determined by the gelling agent employed Clays (Table 10.1–0. * The resultant gel is opalescent. approximately 15% * It provides gels that have good skin contact and * sorbitol in concentrations of 3–15%. * Bentonite is used in concentrations of 7–20% to formulate dermatological bases. of additives that may be added to help retain water include: Polyvinyl alcohol * Polyvinyl alcohol is useful for preparing quick. therefore less General method of manufacture for gels attractive to the patient. pastes and gels | 169 * In concentrations of 0. carbomer acts as a Humectants lubricant. Examples in concentrations of 0.02–0. Other additives for gels 3 Add water to oil.2%) Alginates Pectin (provided the product is acidic in nature) Chlorhexidine acetate (0.3%) Carbomer Activity is increased if used in combination. stirring continuously. Loss of water from a gel results in a skin forming. Table 10. therefore ensures the medicament has good skin contact.1). * On drying. Carmellose sodium Propylene glycol (10%) has been shown to potentiate the Hypromellose antimicrobial activity Pectin Sodium alginate Tragacanth Phenylmercuric nitrate (0.01% w/v) Hypromellose Methylcellulose Benzoic acid (0.1 Choice of preservative to be used in a gel Preservative Gelling agent Benzalkonium chloride (0. bubbles. 2 Heat water to approximately 90 C. g. As a general rule if it is to be used as a base and the ingredients to be added are coloured (e. 4 Weigh 34 g Yellow/White Soft Paraffin BP on a Class II or electronic balance.5 g 2g Wool Fat BP 50 g 5g 0. 2 Weigh 2 g Cetostearyl Alcohol BP on a Class II or electronic balance.6 Preparation of 30 g of Simple Ointment BP Example label We have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Simple Ointment BP 30 g Product directions.5 g 34 g Point of clarity – Product formula The exact quantity cannot be prepared for an ointment. 5 Place the Hard Paraffin BP into an evaporating dish and melt over a water bath.5 g 2g Hard Paraffin BP 50 g 5g 0. If the ingredients to be added are white or pale in colour (e. page 713): 1000 g 100 g 10 g 40 g Cetostearyl Alcohol BP 50 g 5g 0.170 | Pharmaceutical forms and their preparation Worked examples Example 10. and so a suitable overage must be produced in order to dispense the required amount. 3 Weigh 2 g Wool Fat BP on a Class II or electronic balance. which is often used as a base for other ointments. For External Use Only Do not use after (3 months) Patient name Date of dispensing Product formula (British Pharmacopoeia 1988. Method to prepare 40 g of Simple Ointment BP from the formula above: Note that the melting points of the ingredients are as follows: Cetostearyl Alcohol BP 49–56 C Hard Paraffin BP 50–61 C White/Yellow Soft Paraffin BP 38–56 C Wool fat BP 38–44 C 1 Weigh 2 g Hard Paraffin BP on a Class II or electronic balance. Yellow or White Soft Paraffin BP may be used when making this ointment. .g.5 g 2g White/Yellow Soft Paraffin BP 850 g 85 g 8. Coal Tar Solution BP) Yellow Soft Paraffin BP would be used. Zinc Oxide BP or Calamine BP) White Soft Paraffin BP would be used to produce a more pharmaceutically elegant product. 75 g Hydrous Wool Fat BP 250 g 25 g 2. 7 Stir until cold. Note that the quantity of Strong Coal Tar Solution BP is in grams and so must be weighed.7 Preparation of 20 g Calamine and Coal Tar Ointment BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Calamine and Coal Tar Ointment BP 20 g Product directions. .25 g 3. 8 Weigh 30 g and pack into an amber glass jar.25 g 3. but take care not to overheat).5 g 7.75 g Strong Coal Tar Solution BP 25 g 2. pastes and gels | 171 Example 10.25 g Point of clarity – Product formula The exact quantity cannot be prepared for an ointment.75 g Zinc Oxide BP 125 g 12. For External Use Only Caution may stain hair. and so a suitable overage must be produced in order to dispense the required amount. skin and fabrics Do not use after (3 months) Patient name Date of dispensing Product formula (British Pharmacopoeia 1988.5 g 4. page 706): 1000 g 100 g 10 g 30 g Calamine BP 125 g 12. Example 10.5 g White Soft Paraffin BP 475 g 47. Ointments. See Ointments video for a demonstration of the preparation of an ointment by the fusion method.75 g 14.5 g 0. Label and dispense.6 Continued 6 Remove from the heat and add the other ingredients in descending order of melting point until all are melted in (return to the heat if necessary to ensure even melting.5 g 1.25 g 0.5 g 1. 4 Weigh 14.75 g Strong Coal Tar Solution BP on a Class II or electronic balance. 7 Remove from the heat and add the Hydrous Wool Fat BP. 5 Weigh 7. 6 Place the White Soft Paraffin BP into an evaporating dish and melt over a water bath. .5 g Hydrous Wool Fat BP on a Class II or electronic balance.172 | Pharmaceutical forms and their preparation Example 10. See Ointments video for a demonstration of the preparation of an ointment. 2 Weigh 3.7 Continued Method to prepare 30 g of Calamine and Coal Tar Ointment BP from the formula above: Note that the melting points of the ingredients are as follows: Hydrous Wool Fat BP 38–44 C White/Yellow Soft Paraffin BP 38–56 C 1 Weigh 3. This method would also avoid heating the Strong Coal Tar Solution BP and therefore reduce the volatilisation of some of the coal tar constituents and reduce the risk of sedimentation (see Method section. Label and dispense. 11 Allow the base/powder mixture to cool and add the Strong Coal Tar Solution BP and stir until homogeneous.75 g Calamine BP on a Class II or electronic balance. 8 Transfer the powders to a glass tile and levigate with some of the molten base. well mixed base. Point of clarity – Step 11 The Strong Coal Tar Solution BP cannot be added until the bases are quite cool (less than 40 C) as it is a volatile preparation. 3 Transfer the Calamine BP and the Zinc Oxide BP to a porcelain mortar and triturate together with a pestle. stir until melted to ensure an even.2).75 g Zinc Oxide BP on a Class II or electronic balance. Example 10. 10 Weigh 0.25 g White Soft Paraffin BP on a Class II or electronic balance. 9 Transfer the powder/base mix to the rest of the molten base and stir until homogeneous. 12 Weigh 20 g and pack into an amber glass jar. 4 Weigh 25. pastes and gels | 173 Example 10.8 Preparation of 20 g of Zinc Ointment BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Zinc Ointment BP 20 g Product directions.5 g 25. See Ointments video for a demonstration of the preparation of an ointment. In order to achieve a smooth product. a suitable overage must be produced in order to dispense the required amount.5 g 4. Label and dispense.5 g Zinc Oxide BP on a Class II or electronic balance. page 715): 1000 g 100 g 10 g 30 g Zinc Oxide BP 150 g 15 g 1. Therefore. Method to prepare 30 g of Zinc Ointment BP from the formula above: 1 Weigh 4. A smooth product will be produced if the Zinc Oxide BP is finely sifted and then just mixed with the base. enabling a smooth product to be made.5 g Simple Ointment BP on a Class II or electronic balance. Point of clarity – Step 2 The Zinc Oxide BP is transferred to a mortar so that the size of any lumps can be reduced. but in this case using a semi-solid base rather than a molten base. rather than sifting with a sieve. 6 Triturate the Zinc Oxide BP with the Simple Ointment BP until a smooth product is formed. 5 Transfer the Simple Ointment BP to the glass tile. The particle size reduction of the Zinc Oxide BP in this example has only been achieved by mixing in a mortar. For External Use Only Do not use after (3 months) Patient name Date of dispensing Product formula (British Pharmacopoeia 1988.5 g Simple Ointment BP 850 g 85 g 8. Ointments. Point of clarity – Step 6 To triturate means to mix. 2 Transfer to a porcelain mortar and sir with a pestle.5 g Point of clarity – Product formula The exact quantity cannot be prepared for an ointment as losses will be experienced on transfer. . 7 Weigh 20 g of the product and pack into an amber glass jar. considerably more shear force will need to be applied to the powder and we suggest that the process employed would be more akin to levigation (wet grinding). 3 Transfer the Zinc Oxide BP to a glass tile. 8 g 26. 3 Transfer the Salicylic Acid BP to a glass mortar and grind with a pestle to reduce particle size. 2 Weigh 900 mg Sulphur BP on a Class II or electronic balance. .174 | Pharmaceutical forms and their preparation Example 10.9 Unofficial ointment request from local doctor to prepare 20 g of CCS & S Ointment Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): CCS & S Ointment 20 g Product directions.4 g White Soft Paraffin BP on a Class II or electronic balance 7 Transfer the White Soft Paraffin BP to the glass tile. 4 Add the Sulphur BP and continue mixing.4 g Method to prepare 30 g of CCS & S Ointment from the formula above: Note that when phenol is combined with camphor. For External Use Only Do not use after (3 months) The product contains: Salicylic Acid BP 3% Camphor BP 3% Sulphur BP 3% Phenol BP 3% White Soft Paraffin BP to 100% Patient name Date of dispensing The local dermatology clinic has a formulary which gives the following formula: Salicylic Acid BP 3% Camphor BP 3% Sulphur BP 3% Phenol BP 3% White Soft Paraffin BP to 100% Product formula: 100 g 10 g 30 g Salicylic Acid BP 3g 300 mg 900 mg Camphor BP 3g 300 mg 900 mg Sulphur BP 3g 300 mg 900 mg Phenol BP 3g 300 mg 900 mg White Soft Paraffin BP 88 g 8. 6 Weigh 26. 5 Transfer the mixed powders to a glass tile. a liquid mixture results. 1 Weigh 900 mg Salicylic Acid BP on a Class II or electronic balance. 8 Triturate the powders with the White Soft Paraffin BP until a smooth product is formed. . 10 Transfer to a clean dry glass mortar.9 Continued 9 Weigh 900 mg Camphor BP on a Class II or electronic balance. Ointments. 11 Weigh 900 mg of Phenol BP on a Class II or electronic balance. 14 Triturate until all the liquid is incorporated and a homogeneous product is formed. See Ointments video for a demonstration of the preparation of an ointment. 15 Weigh 20 g of product and pack into an amber glass jar and label. 13 Make a well in the ointment mass and add the liquid mixture. 12 Add the Phenol BP to the Camphor BP and mix together with a pestle. pastes and gels | 175 Example 10. Point of clarity – Step 13 The Camphor BP and Phenol BP are weighed and mixed at the final stage of preparation of the product as both are volatile ingredients. . Product formula: Master formula 100 g 10 g 50 g Salicylic Acid BP 2% 2g 200 mg 1g Betnovate Ointment 98% 98 g 9. label and dispense. See Ointments video for a demonstration of the preparation of an ointment. 5 Transfer to the tile. 2 Transfer to a glass mortar and grind with a pestle to reduce any lumps in the powder. 6 Triturate the Salicylic Acid BP and the Betnovate Ointment together. 3 Transfer the powder to a glass tile. Refer to a diluent directory. remembering the ‘doubling-up’ technique for adequate mixing.8 g 49 g Method to prepare 50 g of Salicylic Acid BP 2% in Betnovate Ointment from the formula above: 1 Weigh 1 g Salicylic Acid BP on a Class II or electronic balance.10 Unofficial ointment request from local doctor for 40 g of Salicylic Acid BP 2% in Betnovate Ointment Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Salicylic Acid 2% in Betnovate Ointment 40 g Product directions. 7 Weigh 40 g of the resultant ointment. 4 Weigh 49 g Betnovate Ointment. pack in an amber glass jar.176 | Pharmaceutical forms and their preparation Example 10. For External Use Only Do not use after (2 weeks) The product contains: Salicylic Acid BP 2% Betnovate Ointment 98% Patient name Date of dispensing The suitability of the product formula must be decided by the compounder. which in this case states that up to 5% of Salicylic Acid BP can be added to Betnovate Ointment. Note: Suitable sources to provide information on the dilution of creams and ointments would be: * NPA Diluent Directory * Product data sheet (Summary of Product Characteristics – SPC) * Reports in the pharmaceutical literature * Personal contact with product manufacturer. Had the formula requested Betnovate Cream this would have been unsuitable as the Salicylic Acid BP causes the cream to crack. 5 g 7. 7 Transfer the White Soft Paraffin BP to the glass tile. . 8 Mix the powders with the White Soft Paraffin BP using a metal spatula and remembering the principle of ‘doubling-up’ when mixing. 2 Weigh 7. pastes and gels | 177 Example 10. 3 Weigh 15 g White Soft Paraffin BP on a Class II or electronic balance. For External Use Only Do not use after (3 months) Patient name Date of dispensing Product formula (British Pharmacopoeia 1988. page 868): 1000 g 100 g 10 g 30 g Zinc Oxide BP 250 g 25 g 2.11 Preparation of 20 g Compound Zinc Paste BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Compound Zinc Paste BP 20 g Product directions.5 g Zinc Oxide BP on a Class II or electronic balance. 5 Add the Starch BP to the mortar and triturate with the pestle to form an evenly mixed powder.5 g Starch BP on a Class II or electronic balance. a suitable overage must be produced in order to dispense the required amount. 4 Transfer the Zinc Oxide BP to a porcelain mortar. Ointments. Method to prepare 30 g of Compound Zinc Paste BP from the formula above: Note that the melting point of the base is as follows: White/Yellow Soft Paraffin BP 38–56 C 1 Weigh 7.5 g 7.5 g Starch BP 250 g 25 g 2.5 g White Soft Paraffin BP 500 g 50 g 5g 15 g Point of clarity – Product formula The exact quantity cannot be prepared for an ointment as losses will be experienced on transfer. Point of clarity – Step 5 A porcelain mortar is used because of the volume of powder involved. Therefore. 9 Triturate until a smooth product is formed. 6 Transfer the powder to a glass tile. 8 g Starch BP 380 g 38 g 3. Example 10. page 868): 1000 g 100 g 10 g 30 g Emulsifying Wax BP 50 g 5g 500 mg 1.5 g 13.8 g 11.5 g Coal Tar BP 60 g 6g 600 mg 1. Therefore.178 | Pharmaceutical forms and their preparation Example 10.4 g Yellow Soft Paraffin BP 450 g 45 g 4. Method to prepare 30 g of Zinc and Coal Tar Paste BP from the formula above: Note the melting points of the ingredients: Emulsifying Wax BP 52 C White/Yellow Soft Paraffin BP 38–56 C . a suitable overage must be produced in order to dispense the required amount.5 g Point of clarity – Product formula The exact quantity cannot be prepared for an ointment as losses will be experienced on transfer.11 Continued 10 Weigh 20 g and pack into an amber glass jar. Label and dispense.12 Preparation of 20 g Zinc and Coal Tar Paste BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Zinc and Coal Tar Paste BP 20 g Product directions. For External Use Only Do not use after (3 months) Patient name Date of dispensing Product formula (British Pharmacopoeia 1988.8 g Zinc Oxide BP 60 g 6g 600 mg 1. Point of clarity – Method An alternative way to prepare this paste would involve melting the base then combining the powders with the molten base and stirring until cooled. See Ointments video for a demonstration of the preparation of an ointment. 5 Weigh 1. dispense and label.2). Point of clarity – Step 4 The powders must be mixed remembering the principle of ‘doubling-up’ in order to ensure even mixing of the powders. using a spatula (preferably ebonite). stirring until cool to make a homogeneous product. 2 Transfer to a porcelain mortar. incorporate the Coal Tar BP. 9 Add the Coal Tar BP and half of the Yellow Soft Paraffin BP to the evaporating basin. This method may be preferred because of the possible problem of toxicity associated with Coal Tar BP.12 Continued 1 Weigh 1. 6 Weigh 1. 13 Weigh 20 g of the paste transfer to an amber glass jar. Example 10. 10 Stir at 70 C until melted. 12 Cool to approximately 30 C and add the powders and stir constantly until cold. 3 Finally. Point of clarity – Method The above method is as recommended by the British Pharmacopoeia. This method would avoid heating the Coal Tar BP and therefore reduce the volatilisation of some of the coal tar constituents and reduce the risk of sedimentation (see Method section. 2 Mix the powders as before but transfer them to a glass tile and incorporate the powders using a spatula. 11 Add the remaining Yellow Soft Paraffin BP stir until melted. See Ointments video for a demonstration of the preparation of an ointment.4 g Starch BP on a Class II or electronic balance. Ointments. 7 Weigh 13. 8 Place the Emulsifying Wax BP into an evaporating dish and melt over a water bath at 70 C.8 g Coal Tar BP on a Class II or electronic balance. 4 Add the Starch BP to the Zinc Oxide BP in the porcelain mortar and stir with the pestle.8 g Zinc Oxide BP on a Class II or electronic balance. . An alternative method would be: 1 Melt the Yellow Soft Paraffin BP and Emulsifying Wax BP together at the lowest possible temperature. pastes and gels | 179 Example 10. 3 Weigh 11.5 g Emulsifying Wax BP on a Class II or electronic balance.5 g Yellow Soft Paraffin BP on a Class II or electronic balance. 1% 40 g Product directions.1% from the formula above: 1 Weigh 50 mg Dithranol BP on a sensitive electronic balance. 5 Triturate Dithranol BP with the Zinc and Salicylic Acid Paste BP. 3 Weigh 49.9 g 9. 2 Transfer to a glass tile.95 g Zinc and Salicylic Acid Paste BP on a Class II or electronic balance. Label and dispense.95 g Acid Paste BP Point of clarity – Product formula The exact quantity cannot be prepared for an ointment as losses will be experienced on transfer. If used. For External Use Only Do not use after (3 months) Patient name Date of dispensing Note: the strength of dithranol paste can vary between 0. See Ointments video for a demonstration of the preparation of an ointment.1% Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Dithranol Paste BP 0. Point of clarity – Steps 1–5 Dithranol BP is extremely irritant and care should be taken when handling.99 g 49. Therefore. Product formula (British Pharmacopoeia 1988.180 | Pharmaceutical forms and their preparation Example 10. Method to prepare 50 g of Dithranol Paste BP 0. 4 Transfer the Zinc and Salicylic Acid Paste BP to the glass tile. remembering the principle of ‘doubling-up’ until a smooth product is formed. the formula would need to be adjusted slightly to allow for the weight of Liquid Paraffin BP used. a suitable overage must be produced in order to dispense the required amount. If large quantities are to be made anecdotal evidence suggests using Liquid Paraffin BP to dissolve the powder prior to addition to the paste because this reduces the likelihood of dispersal of the powder when admixing with the paste.1% and 1%. page 866): 1000 g 100 g 10 g 50 g Dithranol BP 1g 100 mg 10 mg 50 mg Zinc and Salicylic 999 g 99. 6 Weigh 40 g of the product and pack into an amber glass jar. .13 Preparation of 40 g of Dithranol Paste BP 0. pastes date. added to the label of all extemporaneously When packaging a pharmaceutical product into an prepared ointments pastes and gels as all are for ointment jar. In the absence of any official guidance. jars come in a variety of different sizes and it is impor- tant to choose a suitably sized container to match the volume of preparation to be dispensed. Pharmaceutical ointment cal preparations can be found in Chapter 5 (page 93). pastes and gels term ‘Discard after’ or ‘Do not use after’ followed by are intended for external use. This is significantly longer than the suggested and gels discard date for extemporaneously prepared creams * specific points relevant to the expiry of (which is four weeks) owing to the fact that ointments extemporaneously prepared ointments. * additional key points relating to the labelling of Diluted ointments (see Example 10. pastes and gels that have been covered in other sections of the book. An over- cost and appearance issues. In the absence of any guide. page 160). as can occur in preparations containing * ‘For external use only’ – This warning must be coal tar). Obviously it is Labelling important not to use a size of container that is too large The labelling of pharmaceutical ointments. Gels.g. it is suggested that * further notes on the packaging of ointments and pastes are given a three-month discard extemporaneously prepared ointments. and gels See Creams video for a demonstration of the packaging of an ointment. ensure that the product is packed well external use only. pastes and gels. To assist compounders in understanding the extemporaneous preparation of Discard dates ointments. pastes and gels will be given here. pastes and for the volume of preparation to be dispensed for both gels has been covered in Chapter 5 (page 92). it is suggested that gels are given a The packaging of extemporaneous preparations four-week expiry date. An overview of the main considerations for stand the term ‘expiry’ it is suggested that a preferred the packaging of ointments.10) would nor- pharmaceutical ointments. which have a higher water content. view of the main considerations for the labelling of Amber glass jars are preferable to clear glass jars ointments. a suitable container a definite date and/or time. This section will recap the main principles relating to ointments. pastes are less susceptible to microbial contamination and gels (see Chapter 9. become available and although cheaper than glass the following points need to be taken into consi- jars. pastes and gels. More recently. pastes final product with a professional appearance. mally be given a two-week discard date. as they protect the preparation from degradation In addition to the standard requirements for by light. This will produce a relating to ointments. this section contains the Some official texts may give a suggested discard date following: for extemporaneously prepared ointments. poraneously compounded products is to apply the As all pharmaceutical ointments. pastes and gels | 181 Summary of essential principles and that no air pockets are visible. will Packaging attract a shorter discard date. are less preferable because of an increased deration: likelihood of the products reacting with the con- tainer (e. plastic ointment jars have the labelling of extemporaneous preparations. would be either an amber wide-necked ointment jar Further guidance on expiry dates to pharmaceuti- or metal collapsible tube. . pastes and gels will be method of indicating shelf-life on the label of extem- given here. Ointments. pastes and gels. has been covered previously in Chapter 5 (page Remember that as patients frequently misunder- 97). 182 | Pharmaceutical forms and their preparation * ‘Store below 15 C’ – Depending on the preparation) but may be advisable if the patient is temperature of the environment. it may be travelling to a location with a warmer climate. . advisable to place a storage temperature warning on the label.10. Table 5. This would not normally be necessary Further guidance on auxiliary labelling can be in the UK (depending on the ingredients within the found in Chapter 5. tration. volume and consistency of administration suppositories are suitable for rectal adminis. * they can be used for patients who are unconscious. Suppositories may contain medicaments. The bases used such as diluents. lubricants. and colouring matter.11 Suppositories and pessaries Introduction and overview 183 Formulae requiring percentage calculations 186 Suppositories 183 General method for suppository preparation 186 Pessaries 184 Worked examples 187 General principles of suppository and pessary Summary of essential principles relating to preparation 184 suppositories and pessaries 192 Suppository mould calibration 184 Packaging 193 Displacement values 185 Discard dates 193 Calculations using displacement values 185 Labelling 193 Introduction and overview They contain one or more active substances dispersed or dissolved in a suitable basis Suppositories which may be soluble or dispersible in water Suppositories are solid unit dosage forms suitably or may melt at body temperature. Alternatively the medica- ments or the base itself may be intended to exert a local The advantages of suppositories as dosage forms action. Suppositories are prepared extemporaneously are that: by incorporating the medicaments into the base and * they can be used to exert a local effect on the rectal the molten mass is then poured at a suitable tempera- mucosa (e. antimicrobial preservatives solve or disperse when in contact with mucous secre. etc. Excipients shaped for insertion into the rectum. anaesthetic. adsorbents. etc. may be added if dissolved or dispersed in the base. The shape. single-dose prepara.) ture into moulds and allowed to cool until set. . fitting or vomiting. agents. which are intended necessary. * they can be used to promote evacuation of the The British Pharmacopoeia (BP) definition is as bowel follows: * if a particular drug causes irritation of the Suppositories are solid.g. to exert a systemic effect. gastrointestinal tract this can be avoided by rectal tions. surface-active either melt when warmed to body temperature or dis. competent authority. authorised by the tions. For Can be used in unconscious Unpredictable and variable patients (e. 2 g or 4 g. Typical sizes are 1 g. Many synthetic fats have been formulated to preparation of pessaries. agents. adsorbents. to include a suitable excess calculate for 10. lubricants. or may melt at body temperature. see Chapter 5 (page 80). antimicrobial preservatives ries as dosage forms are summarised in Box 11. Excipients such as diluents. use of a base other than Pessaries are a type of suppository intended for vaginal Theobroma Oil BP will require recalibration of the use. The larger size moulds are usually used in the moulds. However. General principles of suppository Box 11. Common ingredients for inclusion in pessaries for To recalibrate a suppository mould. delivery and has the added advantage of avoiding bacterial and monilial infections. if you are required to dispense six supposi- Can be used for systemic tories. this is not the case for do exert a systemic effect. usually ovoid. . and colouring matter authorised by the com- petent authority may be added. The British Pharmacopoeia (BP) definition is as The disadvantages of suppositories as dosage follows: forms are that: Pessaries are solid. Because the moulds Pessaries are filled volumetrically.g.1 Advantages and disadvantages of and pessary preparation suppositories as dosage forms The methods used in the preparation of pessaries are Advantages Disadvantages the same as those for suppositories. therefore the mould sizing will be the same and not tion. first-pass metabolism by the liver. They contain one or more active or physically compromised patients substances dispersed or dissolved in a suitable * they have unpredictable and variable absorption basis that may be soluble or dispersible in water in vivo. In this chapter. * they may be unacceptable to certain patients/ They have various shapes. surface-active The advantages and disadvantages of supposito. Can exert local effect on May be unacceptable to points relating to suppositories can also apply to pes- rectal mucosa certain patients saries. match the specific gravity of Theobroma Oil BP and Pessaries are used almost exclusively for local medica. such as 4 g and 8 g moulds. all synthetic bases. during fitting) absorption in vivo example. bases.184 | Pharmaceutical forms and their preparation * systemic absorption can be achieved by rectal * various therapeutic agents to treat trichomonal.1. the exception being prostaglandin pessaries that require recalibration. with cultures a volume and consistency suitable for insertion * they may be difficult to self-administer by arthritic into the vagina. * antiseptics These can then be weighed and the total weight * contraceptive agents divided by the number of suppositories present to find * local anaesthetics the mould calibration value. single-dose preparations.g. the com- local action include: pounder needs to prepare a number (e. if necessary. For further details on suppository and pessary Used to promote evacuation May be difficult to self. of bowel administer by arthritic or The preparation of suppositories invariably Avoids any gastrointestinal physically compromised involves some wastage and therefore it is recom- irritation patients mended that calculations are made for excess. absorption of drugs and avoids first-pass metabolism Suppository mould calibration Suppository moulds are calibrated in terms of the weight of Theobroma Oil BP each will contain. five) of (per- fectly formed) suppositories containing only the base. 4 itory.3 until around two-thirds of the base has Aspirin BP 1.1 melting point. Morphine Sulphate BP 1.2 Resorcinal BP 1. page 174 (also see Table 11. trim the tops and Hydrochloride BP then leave the suppositories to set Hydrocortisone BP 1.6 and divide the total weight by the number of suppositories weighed. For terms of weight then a calculation based on displace- example.0 residual heat to melt the remaining synthetic base. Chloral Hydrate BP 1. e. Hard Fat can be found in Table 11. Calculations using displacement values The displacement value is defined as the quantity If the active ingredient in a suppository is expressed in of medicament that displaces one part of the base.5.7 Problems also arise when medicaments are added to BP the base.7 from the heat and stirred.1.e. using the Castor Oil BP 1. For ease of calculation this is expressed in terms of a series This means that 1.1 Calibrate a 1 g mould drugs incorporated into suppositories with a synthetic base Medicament Displacement value 1 The synthetic base is melted in an evaporating basin over a water bath Aminophylline BP 1. (British) Pharmaceutical Codex 12th edition. 2 The evaporating basin is then removed Bismuth Subgallate BP 2. 5 Weigh all the perfect suppositories Metronidazole BP 1.1 Displacement values of some common Example 11.7 dient is required to be incorporated into each suppos- Zinc Sulphate BP 2.1 Phenobarbital Sodium BP 1.1 melted.6 This will give the value that should be Paracetamol BP 1. . where the displacement value 1 g of the suppository base (Theobroma Oil BP or of an ingredient is defined as the number of parts by Hard Fat BP).6 Displacement values Theophylline Sodium Acetate 1.7 (i.g. where the density of the medicament differs from that of the base and a specific quantity of ingre.g.4 3 When the base has cooled to close to its Codeine Phosphate BP 1. Hydrocortisone BP has a displacement value ment values will need to be made in order to determine of 1. Zinc Oxide BP 4.5 Sulphur BP 1.5 completely. the amount of Hard Fat BP required.5 g Hydrocortisone BP displaces of displacement values. Suppositories and pessaries | 185 Table 11.1). The amount of base displaced will depend on the densities of the ingredients and the base. Diphenhydramine 1. e. BP). avoiding any chipped suppositories) Morphine Hydrochloride BP 1. weight of the ingredient that displaces one part of A summary of some common displacement values Theobroma Oil BP (or other fatty base.5 used for this particular mould with this base. Phenobarbital BP 1. Displacement values are given in standard texts.3 4 After around 5 minutes. it is poured into the mould and allowed to overfill slightly. 55 g of base. use Liquid Paraffin suppository suppositories BP).2 Prepare six codeine mould but do not over-tighten the screw.4 g run down the sides of the mould (if this happens.) For one For 10 10 Pour the mass into the mould uniformly in one suppository suppositories movement. This can easily be achieved 1 Most moulds prepare six suppositories. The substance should be rubbed If the active ingredient in a suppository is expressed in into the minimum quantity of molten base on a terms of a % w/w then a calculation based on displace. trim off the preparation excess Hard Fat BP. when the suppositories 2 Choose a suppository mould to provide the have set. Look for a slight suppositories each containing 6% sheen on the surface of the mass. remainder of the base.6 g) 10 C less than the melting point. General method for suppository 12 When the suppositories have contracted.3 Prepare five usually judged by experience. tile using a spatula.6 g displaces (1 0. but this is not required when using Hard Fat BP. (This is Example 11. simply a gritty product. suppositories with your nails). loosen the screw and tap once sharply suppositories of the required size (usually a 1 g on the bench. Remove the suppositories size). (There should 1.g. similar to a skin copper sulphate w/w forming on custard as it cools. Therefore 0. resulting in the suppository as a proportion. Codeine 60 mg 600 mg Phosphate BP 5 If the suppository is to contain insoluble. The ‘shearing’ effect will not ment value will not be required.) Hold the fatty base needed is 10 0.1 ¼ 0. may change its physical characteristics.186 | Pharmaceutical forms and their preparation 3 Check that the mould is clean and assemble the Example 11. 6 It is important not to overheat the base. Find the Hence 1. evaporating basin in the palm of your hand and stir (do not use the thermometer to stir) to complete the melting process. coarse Hard Fat BP sufficient to fill sufficient to fill powders these must be ground down in a glass 1 1 g size mould 10 1 g size moulds mortar before incorporation. Copper Sulphate BP 60 mg 600 mg 11 Allow the mixture to overfill slightly but not to Hard Fat BP to 1 g ¼ 940 mg to 10 g ¼ 9. stirring constantly. it is likely to be due to the mixture still being too hot). Therefore.45 g. Therefore the amount of still be some solid base present.55 g ¼ 9. phosphate suppositories 60 mg 4 For some suppository bases it is necessary to For one For 10 lubricate the mould (e.1 g of codeine phosphate displaces 1 g melting point of the base and heat it to about 5– of base. . (usually a multiple of 10). but it is by rubbing the flat blade of the spatula over the necessary to calculate to include an excess top of the mould. 13 After further cooling. but before they have set completely. The drug is present in be obtained if too much base is used. subtract the total weight of the medicament from the 8 The paste obtained in step 7 above should be total weight of the fat to determine the amount of fat returned to the evaporating basin with the required. which Displacement value for codeine phosphate is 1. 9 The molten mass should be poured into the mould when it is just about to solidify. 7 Immiscible liquids and insoluble solids should Formulae requiring percentage be incorporated into the fatty base by levigation calculations (wet grinding). Check that the two halves of the mould are carefully (avoid overhandling or damaging the matched (numbers are etched on the sides).1. Suppositories and pessaries | 187 14 Pack the required number of suppositories See Suppositories video for a demonstration individually in foil and place in an amber wide.2. a 2 g mould for a child’s glycerol suppository and a 4 g mould for an adult’s glycerol suppository).5 g Purified water to 100 % 16 g 1.6 g 0.8 g 4g Point of clarity – Product formula The choice of suppository mould for a child’s glycerol suppository is traditionally 2 g (a 1 g mould is usually used for an infant’s glycerol suppository. an overage will need to be prepared to successfully prepare this quantity. positories. etc. If this is not known. To calculate correctly the quantities required the amount that would be required to fill the nominal weight will need to be multiplied by a factor of 1. Point of clarity – Step 1 Care should be taken when using Arachis Oil BP to ensure that the patient does not have any nut allergies. Worked examples Example 11. The glycero- gelatin base has a greater density. of the preparation and packaging of sup- necked jar. . The mould will have been calibrated for use with Theobroma Oil BP or Hard Fat BP.5 g 17.2 ¼ 24 g.4 Preparation of six child-size Glycerol Suppositories BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Glycerol Suppositories BP (2 g) 6 Product directions.4 g 0. page 889): Master formula 100 g 10 g 5g 25 g Gelatin BP 14 % 14 g 1. Method: 1 Prepare the mould by lubricating it with either Arachis Oil BP or Liquid Paraffin BP. sufficient quantities of ingredients to prepare 25 g of base are used. For ease of calculation and weighing. For Rectal Use Only Do not use after (3 months) Patient name Date of dispensing Product formula (British Pharmacopoeia 1988. therefore the nominal weight required to fill the moulds will be greater than with the other two bases.5 g Glycerol BP 70 % 70 g 7g 3. The mass of base that would be needed to prepare 10 child-size (2 g suppositories) is 10 2 1..7 g 3. Calculations are therefore based on the amounts required to prepare 10 suppositories. Calculations: Six suppositories are required. it would be safest to use Liquid Paraffin BP. however. Point of clarity – Product * This glycero-gelatin base is used as a carrier base for other medicaments in some instances. 4 Heat the Glycerol BP over a water bath to 100 C. but as an added precaution when used for pessaries the base may be heat treated by steam at a temperature of 100 C for 1 hour (this is prior to making up to weight and prior to the addition of any thermolabile ingredients). Pharmaceutical grade gelatin should be pathogen free. the use of excess water aids the dissolution of the Gelatin BP.4 Continued 2 Weigh approximately 10 g of purified water and place in a previously weighed evaporating basin.5 g Gelatin BP on a Class II or electronic balance. taking care not to overfill as the base does not contract upon cooling. * Patients with strict religious beliefs and vegetarians may object to the use of animal gelatin (although non-animal gelatin may be available). 11 Pour the mass into the mould.188 | Pharmaceutical forms and their preparation Example 11. wrap. pack and label. Point of clarity – Step 2 The weight of the evaporating basin will be needed for the final adjustment of the weight of the product. 12 Leave to cool then remove from the mould. 10 Adjust the weight by adding sufficient hot water or by evaporation of any excess water. 7 Remove from the heat (to prevent excess evaporation). . See Suppositories video for a demonstration of the preparation and packaging of suppositories. * Gelatin BP may be contaminated with pathogenic microorganisms because of its origin. Point of clarity – Step 9 Stir gently and not too vigorously to prevent the incorporation of air bubbles. An excess of water is used to allow for evaporation and in addition.5 g of Glycerol BP on a Class II or electronic balance and place in an evaporating basin. 9 Add the hot Glycerol BP to the solution and stir until homogeneous. 6 Heat the water to boiling point. * Insoluble substances are rubbed down on the tile with a little of the Glycerol BP (Glycerol BP and not the base is used as it is difficult to re-melt solidified base). 3 Weigh 17. 5 Weigh 3. * Water-soluble thermolabile ingredients are dissolved in a little water before being added to the molten mass. 8 Add the Gelatin BP powder to the water and stir to dissolve. 2. .5 g Glycero-gelatin base 95 % 95 g 9.5 g Calculations: Three pessaries are required. etc. Because the active ingredient to be incorporated in these pessaries is Ichthammol BP.5 g 47.. type B should be used to avoid incompatibilities. sufficient quantities to prepare 50 g are as follows: Master formula 100 g 50 g Gelatin BP 14% 14 g 7g Glycerol BP 70% 70 g 35 g Purified water to 100% 16 g 8g Point of clarity – Formula The British Pharmacopoeia states that purified gelatin can be produced by two different methods: * Partial acid hydrolysis (type A [anionic] gelatin) * Partial alkaline hydrolysis (type B [cationic] gelatin).5 Preparation of three 8 g Ichthammol BP Pessaries 5% Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Ichthammol Pessaries 5% 3 Product directions. Point of clarity – Calculations The glycero-gelatin base has a greater density. therefore the nominal weight required to fill the moulds will be greater than with the other two bases (Theobroma Oil BP and Hard Fat BP). To calculate the quantities required correctly the amount that would be required to fill the nominal weight will need to multiplied by a factor of 1. For Vaginal Use Only Do not use after (3 months) Each pessary contains: Ichthammol BP 5% Glycero-gelatin Base BP 95% Patient name Date of dispensing Product formula: Master formula 100 g 10 g 50 g Ichthammol BP 5% 5g 0. Suppositories and pessaries | 189 Example 11. For ease of calculation and weighing.5 g 2.2 ¼ 48 g. but an overage will need to be prepared to successfully prepare this quantity. The mass of base that would be needed to prepare five pessaries is 5 8 1. Calculations are therefore based on the amounts required to prepare five pessaries. 5 g of the base needs to be replaced by Ichthammol BP. remove from the mould. Point of clarity – Step 1 Care should be taken when using Arachis Oil BP to ensure that the patient does not have any nut allergies. it is easier to remove any excess base rather than try to weigh the amount of base required and transfer to another vessel. If this is not known.190 | Pharmaceutical forms and their preparation Example 11. pack and label. 4 Weigh 47. wrap. it would be safest to use Liquid Paraffin BP.4 above. 2 Prepare the base as in Example 11.5 Continued Method: 1 Prepare the mould by lubricating it with either Arachis Oil BP or Liquid Paraffin BP. 3 Weigh 2. Point of clarity – Step 4 Because the base was prepared in a tared container. . It would not be correct to adjust the base weight by evaporation as this would mean that the Ichthammol BP was replacing water not base. 5 Remove the base from the heat and add the Ichthammol BP.5 g of base. This amount of base needs to be removed. 6 Stir until homogeneous and then pour into the lubricated mould. 7 Leave the pessaries to cool. Note: 2.5 g of Ichthammol BP on a Class II or electronic balance. 7 Castor Oil BP 1. Displacement values: Bismuth Subgallate BP 2.6 1 g Hard Fat BP ¼ 0. The quantity to be used must be calculated using displacement values. A nominal 1 g mould is used. page 723): 1 suppository 10 suppositories Bismuth Subgallate BP 200 mg 2g Resorcinol BP 60 mg 600 mg Zinc Oxide BP 120 mg 1.0 Bismuth Subgallate BP displaces 2 2.74 þ 0.2 4.6 1.5 Zinc Oxide BP 4.2 g Castor Oil BP 60 mg 600 mg Base qs qs Point of clarity – Product formula Hard Fat BP is a suitable base to use.5 g Hard Fat BP ¼ 0.6) ¼ 10 – 2.00 ¼ 8.26 g Castor Oil BP displaces 0.4 g Zinc Oxide BP displaces 1.7 g Hard Fat BP ¼ 0.00 g .7 g Hard Fat BP ¼ 0.6 Preparation of six Compound Bismuth Subgallate Suppositories BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Compound Bismuth Subgallate Suppositories BP 3 Product directions.26 þ 0. For Rectal Use Only Do not use after (3 months) Patient name Date of dispensing Product formula (British Pharmacopoeia 1980.4 þ 0. Calculations: Prepare for 10 suppositories to allow for losses during preparation.74 g Resorcinol BP displaces 0.7 Resorcinol BP 1. Suppositories and pessaries | 191 Example 11.6 g The amount of base required ¼ (10 1 g) – (0. 4 Weigh 600 mg Resorcinol BP on a Class II or electronic balance.2 g Zinc Oxide BP on a Class II or electronic balance. dry matched suppository mould and allow to set.6 Continued Working formula: 10 suppositories Bismuth Subgallate BP 2g Resorcinol BP 600 mg Zinc Oxide BP 1.192 | Pharmaceutical forms and their preparation Example 11. 8 Levigate the powders with the Castor Oil BP and a little molten base. See Suppositories video for a demonstration of the preparation and packaging of suppositories. understanding the extemporaneous preparation of suppositories and pessaries. 10 Stir until almost set then transfer to a clean. 3 Weigh 2 g of Bismuth Subgallate BP on a Class II or electronic balance.2 g Castor Oil BP 600 mg Hard Fat BP 8g Method: 1 Weigh 8 g of Hard Fat BP on a Class II or electronic balance. To assist compounders in pharmaceutical suppositories and pessaries. 2 Transfer to an evaporating basin and melt over a water bath. this section contains: . 9 Return the resultant mix to the molten mass and stir. 11 Trim the tops and remove from the mould. Point of clarity – Step 6 Any liquid ingredients to be added to suppositories must be weighed NOT measured. Summary of essential principles * further notes on the packaging of extemporaneously prepared suppositories and relating to suppositories and pessaries pessaries * specific points relevant to the expiry of extemporaneously prepared suppositories and This section will recap the main principles relating to pessaries suppositories and pessaries that have been covered in * additional key points related to the labelling of other sections of the book. 5 Weigh 1. 7 Mix the powders together in a mortar using the ‘doubling-up’ technique and transfer to a warmed tile. 6 Weigh 600 mg Castor Oil BP on a Class II or electronic balance. 12 Wrap individually in foil and transfer to an amber glass jar and label. suppositories can be placed in an ointment jar or card- board carton and labelled. In practical terms it is suggested that an expiry date of three months is given to suppositories and pessaries in Further guidance on auxiliary labelling can be the absence of any official guidance. . factured in metal moulds should be removed from the Further guidance on expiry dates to pharma- mould carefully and individually wrapped in suitably ceutical preparations can be found in Chapter 5 sized pieces of aluminium foil. found in Chapter 5. the follow- suppositories from the disposable mould and wrap ing points need to be taken into consideration: and package as for those prepared in metal moulds. * ‘Store below 15 C’ – This warning must be added Discard dates to the label of all suppositories and pessaries. the (page 92). the packaging of suppositories.10. the term ‘Discard after’ or ‘Do not use after’ followed Suppositories and pessaries that have been manu. Labelling Suppositories that have been manufactured in a The labelling of pharmaceutical suppositories and pes- disposable mould are often dispensed to the patient saries has been covered in Chapter 5 (page 91). An in the mould. it will be necessary to remove the labelling of extemporaneous preparations. * ‘For vaginal use only’ – This warning must be added to the label of any pessaries. * ‘For rectal use only’ – This warning must be added See Suppositories video for a demonstration of to the label of any suppositories. Table 5. Sometimes. Suppositories and pessaries | 193 Packaging Remember that because patients frequently misun- The packaging of extemporaneous preparations has derstand the term ‘expiry’ it is suggested that a pre- been covered in Chapter 5 (page 96). by a definite date and/or time. An overview of ferred method of indicating shelf-life on the label of the main considerations for the packaging of suppos. and that the label is placed on a suitable part of the In addition to the standard requirements for the mould. It is important to ensure that the patient overview of the main considerations for the labelling will be able to release each suppository from the mould of suppositories and pessaries will be given here. Once wrapped. extemporaneously compounded products is to apply itories and pessaries will be given here. . discourages This section will include solid preparations intended bacterial growth and has a cooling effect. can be contaminated with microorganisms and must These are dry. . is organic and can support microbial growth.1. ders as dosage forms are summarised in Box 12. although an excellent dusting powder. * They are easy to apply. granulomas. despite being an inert compound. causing irritation. The advantages of dusting powders as pharmaceu. which leads to reduced friction between skin surfaces. – Starch. Bulk powders for external use – Talc. * individual unit dose powders * There is a possibility of contamination: * unit dose capsules. The following types The disadvantages of dusting powders as pharma- of preparation will be considered: ceutical products are as follows: * bulk powders for external use – termed dusting * They may block pores. The advantages and disadvantages of dusting pow- * They are pleasant to use. free-flowing preparations consisting of therefore always be sterilised prior to one or a mixture of finely powdered substances and incorporation into a dusting powder. for both internal and external use. intended for external application. * Light fluffy powders may be inhaled by infants. or if powders applied to parietal surfaces.12 Powders and capsules Introduction and overview 195 Unit dose capsules 199 Bulk powders for external use 195 General method of preparation of capsules 201 Formulation 196 Worked examples 202 General method for preparing dusting Summary of essential principles relating powders 196 to powders and capsules 205 Bulk oral powders 196 Packaging 205 Individual unit dose powders 197 Discard dates 206 Calculations for powders 198 Labelling 206 General method for producing unit dose powders 199 Introduction and overview * They absorb skin moisture. fibrosis * bulk oral powders or adhesions. tical products are as follows: * They are not suitable for application to broken skin. causing breathing difficulties. Some dusting Tannic Acid BP powders incorporate medicaments. giving them anti- Cooling antipruritic ingredients Camphor BP bacterial or antifungal action. Preparations in this group are formulated on the General method for preparing dusting basis of dose-weights. Sulphur BP Dusting powders are applied to the skin for a sur. which can cause tetanus and gangrene. Clostridium welchii and Bacillus anthracis. page 118). which is considered to be the a dusting powder is the standard ‘doubling-up’ tech. including Miscellaneous ingredients added to dusting powders: Clostridium tetani. kaolin White. * Chlorhexidine Dusting Powder BP – Used for its Bulk oral powders antibacterial effect.1 Common ingredients included in Box 12. It is obvious that both the nique (see Key Skill 7. ‘doubling-up’ technique. accuracy and precision of the dosage will be signifi- See Powders video for a demonstration of the cantly influenced by a large number of varying factors.g. Astringents Aluminium Chloride BP face effect such as drying or lubrication. These include the density of the powders used. The measure of volume used is The method for mixing powders in the formulation of a heaped 5 mL spoonful. whereas the dose is actually powders measured by volume.1. The dose to be taken is measured with a 5 mL spoon. with good covering Talc BP and other natural mineral substances are liable to properties Zinc Oxide BP be heavily contaminated with bacteria. equivalent to 5 g of powder. expected standards of precision of dosage. tion. this method of measurement ders and the properties they contribute are listed in creates considerable problems with regard to the Table 12. Antibiotics Boric Acid BP (not used in Therefore. . stirred into a quantity of water and then swal- Common ingredients included in dusting pow- lowed. * Tinaderm Powder – A proprietary product used Bulk oral powders resemble dusting powders with the for the treatment of fungal infections (e. Unfortunately. the interpretation of ‘heaped’ 5 mL spoon by the patient. Examples include: Menthol BP * Thymol BP Talc Dusting Powder BP – Used as a lubricant to prevent chafing.1.196 | Pharmaceutical forms and their preparation Table 12. such ingredients must have been sterilised modern preparations) before use. Tinea exception that they are intended for oral administra- infections such as athlete’s foot).1 Advantages and disadvantages of dusting powders and their properties dusting powders as dosage forms Properties Ingredients Advantages Disadvantages Easy to apply May block pores causing Absorbent Bentonite BP Pleasant to use irritation Kaolin BP Absorb skin moisture Possibility of contamination Starch BP Decreasing skin friction Light fluffy powders may be Talc BP Discouraging bacterial growth inhaled by infants leading to Drying action gives cooling breathing difficulties Dispersing and lubricating for Starch BP effect Not suitable for application ease of application Talc BP to broken skin Adhesives that help the powder Aluminium Stearate BP to stick to the skin Magnesium Stearate BP Zinc Stearate BP Increase 'lightness and Prepared Chalk BP Formulation fluffiness' Zinc Stearate BP Some commonly used ingredients such as talc. overcome by providing the patient with a set of separate Bulk powders may be a single powder (e. medicines (POM) (e. This is particularly true if they contain ingredi- liquid equivalent Bulky and inconvenient to carry ents intended to produce effervescence.2. powders as dosage forms are summarised in Box 12.e. inconvenient to carry Powders are useful for administration to children * it is difficult to mask any unpleasant taste. They may be taken by The advantages and disadvantages of bulk oral pouring onto the back of the tongue and swallowing. to protect the Administered with relative Difficult to mask unpleasant contents from moisture. * the accuracy of dosage is not guaranteed. Andrews Salts. The diluent used is normally Lactose BP as it is therefore it is not a suitable dosage form for potent colourless.g. each of which has been individually wrapped. There are a number of proprie- powders is the same as that for dusting powders (see tary brands of individual powders of prescription-only page 196).g.The advantages of unit dose ease tastes powders as pharmaceutical products are as follows: Absorption quicker than capsules or tablets * They show greater stability than liquid dosage forms as the rate of reaction between drugs in a . Bisodol Indigestion Relief of each powder should be 200 mg. doses. our recommended Powder and Eno Powder. or alternatively they may be added to a small amount of The method used in the manufacture of bulk oral water and swallowed. The weight Powder. Magnesium Trisilicate Powder BP) or a mix of several Single-dose powders usually consist of one or more powders (e.2 Advantages and disadvantages of dration sachets (Dioralyte). Powders that have been Advantages Disadvantages commercially manufactured are often packed in sealed May be more stable than Variable dose accuracy sachets.g.g. who cannot swallow tablets. folded to a uniform shape and size. * 200 mg is the amount of powder that will fit into a size 3 capsule and. is chosen because: ceutical products are that: * 200 mg can be weighed on a Class II balance (or * dry powders may be more stable than their liquid electronic equivalent) (i. it would make sense to The disadvantages of bulk oral powders as phar- use the same calculations for both powders and maceutical products are that: capsules (see page 198). Calcium Carbonate Compound Powder powdered active medicaments. for ease. diluent. weight. where such products are intended for ders and bulk oral powders is that the dosage problem is the symptomatic relief of minor ailments. Starch BP is an * the large size container means that they may be alternative diluent if the patient is lactose intolerant. Powders and capsules | 197 etc. Consequently. This weight The advantages of bulk oral powders as pharma. Stemetil Powders (prochlorpera- zine)) and powders readily available as over-the-counter (OTC) medicines include Beechams Powders. this formulation is restricted to use Individual unit dose powders in preparations consisting of relatively non-potent medicaments such as Kaolin BP and Magnesium The sole difference between individual unit dose pow- Trisilicate BP. Fennings Children’s bulk oral powders as dosage forms Cooling Powders and Resolve. oral rehy- Box 12. indigestion powders) calculations (it is easy to undertake calculations * absorption from the gastrointestinal tract will be using multiples or divisions of 200) quicker than with capsules or tablets. for ease of handling by the patient. and wrapped as single doses in white demy Common proprietary products include Actonorm paper. Paramax Powders (paracetamol and metoclopramide). 200 mg is greater than equivalent the minimum weighable quantity of the balance) * large doses of bulky powders may be administered * 200 mg is an easy figure to use in pharmaceutical with relative ease (e. together with an inert BPC 1973). soluble and harmless and therefore shows medication the ideal properties of an inert diluent. 1750 mg) reduced local irritation of the gastrointestinal tract which may be caused by local concentration So long as the final quantities to be weighed are of a drug. This Calculations for powders limit is based on an initial mix (including an excess) for 10 powders. weighable quantity of a Class II balance (see Chapter The two different calculations are termed single dilu- 4. * The small particle size leads to more rapid For one powder for 10 powders absorption from the gastrointestinal tract Furosemide BP 25 mg 250 mg compared with tablets. if the prescription is for five * They are easy to administer. Small particle size of drug dilution would be required is to a certain extent arbi- Acceptable to patients trary and really a matter of professional judgement. including a suitable relatively easy to swallow and may be mixed with excess. Write out the formula for one powder based on a final For example. 175 mg) to 2000 mg (i. amount to be weighed. if a prescription is for five weighing of 200 mg. are must be used. make an excess. attractive to dilution can be used. rather than single. page 55). page 55 and Key Skill 4. the amount of active ingredient to be weighed is below the minimum * They may be difficult to swallow. Then write out the formula for Bromocriptine powders 1 mg. the minimum weighable quantity of the balance and Single dilution therefore require double dilution. If each powder contains 15 mg of There are two main calculations for powders. Remember to always than the rate of reaction in a liquid medium.3.e. * Accurate dosage is possible. double dilution * Unpleasant flavours. weighable quantity of the balance. owing to the Box 12.2). active ingredient will be present in very low concen- trations. 250 mg is the smallest patients and convenient to carry. mum weighable quantity of the balance and so single maceutical products are as follows: dilution will be suitable.3 Advantages and disadvantages of small amount of active ingredient that would be pres- unit dose powders as dosage forms ent. (see Chapter 4. Any smaller quantity would be less than tion and double dilution (or serial dilution). as encountered when taking an above the minimum weighable quantity of the balance equivalent tablet. Powders are Furosemide 25 mg powders. single * They are well accepted by patients. difficult to mask when in powder form. Advantages Disadvantages This might result in ‘clumping’ of the active ingredient. This dient to be incorporated into each powder and the (150 mg) is equal to the accepted usual minimum total number of unit doses (or excess) to be made. the powders as dosage forms are summarised in Box 12. This is greater than the mini- The disadvantages of unit dose powders as phar. By simply multiplying the quantities of the ingredients up to weighable quantities. If. bitter or nauseous. the total for 10 powders will be choice being dependent on the quantity of active ingre- 150 mg of active ingredient (10 15 ¼ 150). Easy to administer The dosage at which serial. More stable than liquid dosage May be difficult to swallow which could have potentially fatal consequences for forms Hard to mask unpleasant Accurate dosing flavours the patient.198 | Pharmaceutical forms and their preparation dosage form in atmospheric conditions is slower the total number of powders. Double dilution (serial dilution) The advantages and disadvantages of unit dose When dosages of very potent drugs are required. a total for 10 powders .e. it would be difficult to ensure that a uniform mix of active ingredient and diluent would be obtained. the active ingredient. calculate for 10 powders: food or drink in order to assist administration. however. In this case. This in turn leads to Lactose BP to 200 mg (i. For example. Our suggested limit is that concentrations of active ingredient below 15 mg require serial dilution. the powder will fall of bromocriptine ¼ 200 mg then 200 mg is 19 times out during opening). 12 Stack the powders. Mix X is: about two-thirds of the width of the paper. Powders and capsules | 199 should be made: 5 Work on a clean dry glass tile. a powder trestle was used to assist the Bromocriptine BP 10 mg ¼ Mix X 200 mg compounder with step 10 above (Figure 12. or due to instability of the ingredients) in a mortar using the ‘doubling-up’ technique (see Chapter 7. 10 cm 10 cm). for ease of handling. 1800 mg) on the top of the trestle. for example if the patient is preparation of a unit dose powder. the flap folded originally. required so single dilution would not be suitable. in pairs. usually powder. The use of a powder trestle ensured that all the powders would be of a uniform size. and turn in For one powder for 10 powders one edge and fold down approximately half an Bromocriptine BP 1 mg 10 mg inch (1 cm). Lactose BP 3800 mg 10 Fold the two ends under. formula. dilution with lactose is required. powders in that each dose of powder is enclosed in an edible container. Unit dose capsules See Powders video for a demonstration of the Capsules are a further development from unit dose ‘doubling-up’ technique. flap to flap. and underneath. 15 The label should be placed on the outer pack 3 Determine whether a single or double dilution of such that when the patient opens the box they do the active ingredient is required. 2 Calculate to make an excess of the number of 14 Place in a rigid cardboard box. The Lactose BP to 2000 mg ¼ to 2000 mg paper containing the powder was placed centrally.1). powders requested. which is swallowed whole with a .g. 7 Weigh out the individual powder from the bulk Therefore. not destroy the label. and then the sides bent under- This will provide 10 powders each containing neath using the edges of the trestle to form neat 10 mg of Bromocriptine BP. 1990 mg) (i. so that the loose ends It is known that 200 mg of Mix X will contain the slightly overlap. creases. This is 15 times more than the 10 mg be used for weighing. and then tuck one flap inside 10 mg of Bromocriptine BP required for the master the other. General method for producing unit 11 Wrap each powder in turn. making sure they are dose powders all the same size. (i.e. Master formula for 10 powders: Historically. greater than the 10 mg required: 8 Fold the bottom of the powder paper up to. and each achievable on a Class II balance for potent substances slightly overlapping. 19 parts of lactose ¼ 19 200 mg ¼ 3800 mg 9 Fold down the top of the paper until it covers Let’s call this concentrate Mix X. 6 Place the papers on the glass tile. tightly). This top edge of this fold should help to hold the Bromocriptine BP 200 mg contents in the centre of the paper. the minimum recommended weight edge away from the compounder. select a suitable size of paper (e.1). Key Skill 7. and transfer to the centre of the paper based on multiples of 200 mg. Repeat for the required number of Lactose BP to 200 mg to 2000 mg powders. intolerant to lactose. 4 Mix the active ingredient and the diluent (Lactose BP unless there is a reason not to use See Powders video for a demonstration of the Lactose BP. the minimum 13 Tie together with a rubber band (not too weight of powder in a unit dose paper is 200 mg. next to the balance pan to is 150 mg.e. with the folded However. Therefore if one part (if placed too near the fold. 1 Remember. Powders show greater stability (although non-animal gelatin capsules may be than liquid dosage forms as the rate of reaction available). Easy to administer Possible problems with the * The smaller particle size of powdered drugs leads Unpleasant tastes easily masked use of animal gelatin to more rapid absorption from the gastrointestinal Release characteristics can be tract compared to tablets.1 A powder trestle.4. * Capsules are unsuitable for very small children. The advantages of unit dose capsules as pharmaceuti. unit dose capsules as dosage forms * Unpleasant tastes can be easily masked.4 Advantages and disadvantages of slippery when moistened). liquid medium. capsules are similar to those of unit dose powders. attractive to released from its container until it is in the stomach. * Advantages Disadvantages The release characteristics of the drugs can be controlled.200 | Pharmaceutical forms and their preparation Figure 12. This in turn leads to controlled reduced local irritation of the gastrointestinal Can be made light resistant tract which may be caused by local concentration Small particle size of drug of a drug as encountered when taking an Acceptable to patients equivalent tablet. The powder is not * They are well accepted by patients. More stable than liquid dosage May be difficult to swallow * forms Unsuitable for very small They can be made light resistant using opaque Accurate dosing children capsules. . between drugs in a dosage form in atmospheric The advantages and disadvantages of unit dose conditions is slower than the rate of reaction in a capsules as dosage forms are summarised in Box 12. This type of presentation is more convenient for the patient. maceutical products are as follows: The advantages and disadvantages of unit dose * They may be difficult to swallow. patients and convenient to carry. and is particularly useful for medicaments The disadvantages of unit dose capsules as phar- which have an unpleasant taste. * Accurate dosage is possible. draught of water (about 30–60 mL). * They are easy to administer – capsules are relatively easy to swallow (suitable shape and Box 12. * Patients with strict religious beliefs and cal products are as follows: vegetarians may object to the use of animal gelatin * They are stable. Powders and capsules | 201 2 Calculate quantities required and make an excess, Table 12.2 Approximate capacities of capsules as with the manufacture of individual unit dose Size of capsule Contents (mg) powders. 3 Mix using the ‘doubling-up’ technique (see Key 000 950 Skill 7.1). 00 650 See Powders video for a demonstration of the 0 450 ‘doubling-up’ technique. 1 300 2 250 4 Handle the capsules as little as possible as powder fill weights will be inaccurate as a result of 3 200 contamination with grease, moisture, etc., and 4 150 also for reasons of hygiene. Fill powder into the longer half of the capsule. 5 100 5 There are at least three methods of filling capsules manually. Always work on a clean tile: remember these capsules are to be swallowed by There are two main basic types of capsule: a patient. * Soft gelatin capsules – These are flexible capsules a Place some powder onto a piece of weighing and may be spherical, ovoid or cylindrical in paper. Hold the capsule with one hand and shape. They are usually used in manufacturing lift the paper with the other and scoop the when they are formed, filled and sealed in one powder into the capsule. operation. Examples of this type of capsule b Place some powder onto a piece of weighing include Atromid S, Efamast, Epogam and paper and fill the capsule using a chemical nifedipine capsules (they tend to be used mainly spatula. for oils, gels, etc.). c Weigh approximately 200 mg of powder * Hard capsules – These are made of hard gelatin onto a piece of weighing paper, which has and formed in two halves. The medicament is been folded in half. Use the weighing paper inserted into the longer portion and the second to pour the powder into the capsule. half fitted. Patients should be instructed to swallow the capsules whole and NOT to open 6 Ensure capsule outer surface is powder free. them. Hard gelatin capsules are available in a Check weight of the filled capsule. Remember to variety of different sizes (Table 12.2). tare with an empty capsule of the same size so you are only weighing the contents of the General method of preparation of capsule (and not including the weight of the capsules capsule itself). 1 Choose an appropriate size capsule for the See Powders video for a demonstration of the powder bulk. Normally a size 3 capsule would be preparation of a capsule. chosen and so work on the basis of filling each capsule with 200 mg of powder (Table 12.2). 202 | Pharmaceutical forms and their preparation Worked examples Example 12.1 Preparation of 100 g of Zinc Starch and Talc Dusting Powder BPC Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Zinc, Starch and Talc Dusting Powder BPC 100 g Product directions. For External Use Only Store in a dry place Not to be applied to open wounds or raw weeping surfaces Do not use after (3 months) Patient name Date of dispensing Product formula (British Pharmaceutical Codex 1973, page 664): 1000 g 100 g Zinc Oxide BP 250 g 25 g Starch BP 250 g 25 g Purified Talc BP 500 g 50 g Method: 1 Weigh 25 g Zinc Oxide BP using a Class II or electronic balance. 2 Weigh 25 g Starch BP using a Class II or electronic balance. 3 Weigh 50 g Purified Talc BP using a Class II or electronic balance. 4 Transfer the Starch BP to a porcelain mortar. 5 Add the Zinc Oxide BP to the Starch BP in the mortar and mix using a pestle. Point of clarity – Step 5 The powders are admixed in order of volume, remembering the ‘doubling-up’ technique (see Key Skill 7.1). 6 Add the Purified Talc BP to the powders in the mortar and continue mixing. 7 Transfer the mixed powder to a ‘powder shaker’ container or an amber glass jar. 8 Label and dispense to the patient. See Powders video for a demonstration of the preparation of a dusting powder. Powders and capsules | 203 Example 12.2 Preparation of 100 g of Compound Magnesium Trisilicate Oral Powder BP Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Compound Magnesium Trisilicate Oral Powder BP 100 g Product directions. Store in a dry place Do not use after (3 months) Patient name Date of dispensing Product formula (British Pharmacopoeia 1988, page 873): 1000 g 100 g Magnesium Trisilicate BP 250 g 25 g Chalk (powdered) BP 250 g 25 g Heavy Magnesium Carbonate BP 250 g 25 g Sodium Bicarbonate BP 250 g 25 g Method: 1 Weigh 25 g Magnesium Trisilicate BP using a Class II or electronic balance. 2 Weigh 25 g Chalk BP using a Class II or electronic balance. 3 Weigh 25 g Heavy Magnesium Carbonate BP using a Class II or electronic balance. 4 Weigh 25 g Sodium Bicarbonate BP using a Class II or electronic balance. 5 Mix the powders in a porcelain mortar in order of bulk volume. Point of clarity – Step 5 The suggested order is Sodium Bicarbonate BP first, then add Chalk BP, Heavy Magnesium Carbonate BP and finally Magnesium Trisilicate BP. The Sodium Bicarbonate BP is noticeably smallest volume and also the most likely to suffer clumping and be lumpy in appearance. 6 Transfer to an amber glass jar, label and dispense to the patient. See Powders video for a demonstration of the preparation of an oral powder. 204 | Pharmaceutical forms and their preparation Example 12.3 Preparation of five individual dose powders of Codeine Phosphate BP 10 mg Example label (we have assumed that the name and address of the pharmacy and the words 'Keep out of the reach and sight of children' are pre-printed on the label): Codeine Phosphate 10 mg powders 6 Product directions. Store in a dry place Do not use after (3 months) Warning: May cause drowsiness. If affected do not drive or operate machinery. Avoid alcoholic drink Each powder contains: Codeine Phosphate BP 10 mg Lactose BP 190 mg Patient name Date of dispensing Product formula: 1 powder 10 powders Codeine Phosphate BP 10 mg 100 mg Lactose BP to 200 mg to 2000 mg Point of clarity – Product formula The final weight of individual powders that we recommend for ease of calculation and administration is 200 mg. An excess is made to allow for losses during preparation. Calculation: The quantity of Codeine Phosphate BP required for the 10 powders is 100 mg, which is below the minimum weighable quantity for a Class II balance, therefore it is recommended to follow the double (serial) dilution process. A concentrated powder (Mix X), each 200 mg of which contains 100 mg Codeine Phosphate BP, needs to be prepared. As 100 mg cannot be accurately weighed, the quantities in Mix X need to be adjusted. To keep Mix X the same concentration, both parts of the concentration ratio must be multiplied by the same factors, i.e. 2 100 mg ¼ 200 mg 2 200 mg ¼ 400 mg Therefore Mix X must have a concentration 200 mg/400 mg (200 mg Codeine Phosphate BP per 400 mg of Mix X). As we must have exact weights the quantities for Mix X are: Codeine Phosphate BP 200 mg Lactose BP 200 mg (i.e. to 400 mg) Powders and capsules | 205 Example 12.3 Continued Therefore the final formula for preparation for the 10 powders, Mix Y, will be: Mix X 200 mg (containing 100 mg Codeine Phosphate BP) Lactose BP to 2000 mg (1800 mg) Method for preparing Codeine Phosphate 10 mg unit dose powders using the above formula: 1 Weigh 200 mg Codeine Phosphate BP using a Class II or electronic balance. 2 Transfer to a porcelain mortar. 3 Weigh 200 mg Lactose BP using a Class II or electronic balance. 4 Add the Lactose BP to the Codeine Phosphate BP in the mortar using the ‘doubling-up’ technique. 5 This is Mix X. 6 Weigh 200 mg Mix X using a Class II or electronic balance and transfer to a clean dry mortar. 7 Weigh 1800 mg Lactose BP using a Class II or electronic balance. 8 Add the Lactose BP to the Mix X in the mortar using the ‘doubling-up’ technique. 9 This is Mix Y. 10 Weigh 200 mg aliquots of the Mix Y and wrap as individual dose powders. 11 Pack the powders flap to flap and enclose with a rubber band. 12 Pack into a cardboard box and label. See Powders video for a demonstration of the preparation of a unit dose powder. Summary of essential principles Bulk powders for external use Bulk powders for external use are either packaged as relating to powders and capsules for bulk oral powders or in a powder shaker with a This section will recap the main principles relating to sifter top. powders and capsules that have been covered in other See Powders video for a demonstration of a sections of the book. To assist compounders in under- powder shaker with a sifter top. standing the extemporaneous preparation of powders and capsules, this section contains: Bulk oral powders * further notes on the packaging of Bulk oral powders are usually packaged in an airtight extemporaneously prepared powders and capsules glass or plastic jar. It is important that the preparation * specific points relevant to the expiry of is not exposed to moisture as this will result in clumping extemporaneously prepared powders and capsules of the product and may encourage microbial growth. * additional key points related to the labelling of pharmaceutical powders and capsules. Individual unit dose powders Once made, individual unit dose powders are placed flap to flap and secured together by a rubber band. The Packaging whole set of powders is then placed in a rigid card- The packaging of powders and capsules is dependent board container and the label is placed on the container on the formulation. before the preparation is dispensed to the patient. 206 | Pharmaceutical forms and their preparation Preparations containing effervescent or deliques- Labelling cent ingredients need to be packed in a sealed con- The labelling of extemporaneous preparations has tainer (e.g. an ointment jar). been covered in Chapter 5 (page 91). An overview of Unit dose capsules the main considerations for the labelling of powders Unit dose capsules are dispensed in a glass or plastic and capsules will be given here. tablet bottle with a child-resistant closure. In addition to the standard requirements for the labelling of extemporaneous preparations, the follow- Discard dates ing points need to be taken into consideration: Proprietary powders and capsules are manufactured in * Bulk oral powders, individual unit dose powders special environments and usually attract a long shelf- and bulk powders for external use are all life. When dealing with extemporaneously prepared susceptible to moisture. For this reason, it is preparations, the compounder must take a number necessary to include the caution ‘Store in a dry of considerations into mind when deciding the length place’ on the label of any of these preparations. of expiry to give a product, such as the stability of the * Dusting powders will also attract the caution ingredients within the preparation and the susceptibil- ‘Not to be applied to open wounds or raw ity of the preparation to microbial contamination. As a weeping surfaces’. general rule, an expiry of up to three months may be * In addition, any preparation intended for external given to any of the preparations in this chapter, use (i.e. bulk powders for external use) would attract although consideration must be given to each individ- the additional caution ‘For external use only’. ual formulation. Remember that as patients frequently misunder- Further guidance on auxiliary labelling can be stand the term ‘expiry’ it is suggested that a preferred found in Chapter 5, Table 5.10. method of indicating shelf-life on the label of extem- In addition to labels about storage, labels for indi- poraneously compounded products is to apply the vidual powders and capsules containing potent ingre- term ‘Discard after’ or ‘Do not use after’ followed by dients may also require British National Formulary a definite date and/or time. additional caution labels. These can all be found in Further guidance on expiry dates for pharmaceu- Appendix 9 of the current edition of the British tical preparations can be found in Chapter 5 (page 92). National Formulary. In many cases. The purpose of licensing medi.g. safety large doses of certain drugs which. how much. ‘one-off’ medication for a normal patients. science) is the branch of medicine/phar. Doses cannot be rigidly responsibility of the pharmacist to satisfy themselves fixed. Posology Scrupulous checking of the dose and frequency of Posology (derived from the Greek posos. efficacy and quality. over a long period of time. diamorphine. liver failure or pregnancy Many items that are dispensed extemporaneously are * any acquired tolerance. For example: unlicensed medicines. such as renal failure. in raneous dispensing process. During the extempo. licence and no stability or safety data available. the concentration of active constitu- ents in products for external use must be checked.13 Specialised formulation issues Introduction and overview 207 The dose check 211 Posology 207 Incompatibilities 212 Paediatric formulations 207 Dermatological extemporaneous formulation 213 Extemporaneous formulations for geriatric patients 210 Introduction and overview * any co-existing disease(s) or condition(s). morphine. cines in the UK is to ensure that they are examined for acquire the ability to take with comparative their safety. all drugs intended for internal use is essential. Similarly. unusual dose appears to have been prescribed it is the macy dealing with doses. * the age of the patient * the weight of the patient * the condition being treated and its severity Paediatric formulations * the route of administration Some medicines are either specifically marketed for * the frequency of administration children or have a product licence for use in both . When an and logos. would produce harmful or particular patient is often prepared and there is no fatal effects. allowances may need to be made that the prescriber’s intention has been correctly inter- for: preted. – Drug addicts can. where killers (e.) and extemporaneous dispensing is widespread. etc. The – Terminally ill patients can also show the same main areas where ad hoc formulations are prepared type of tolerance to high doses of opioid pain are in paediatric medicine and dermatology. the British National Formulary gives some guidelines with regard to doses used in palliative care. it is also termed being used ‘off label’.208 | Pharmaceutical forms and their preparation children and adults. of individual drugs by age. This means that the product licence for the Formulary (BNF) or British National Formulary medication was issued for use in adults and that use in for Children. in order to provide seamless care. if nor- College of Paediatrics and Child Health: mal reference sources found in the pharmacy fail to confirm the safety of a particular preparation with * preterm newborn infant – born at less than 37 regard to dose of active ingredient.uk. * Source of drug: inate in hospitals. * The Neonatal and Paediatric Pharmacists Group dition. Tel: (0151) 252 5837. a product can Formulary for Children (www. Doses cannot be is still responsible for checking that the product formula just determined by comparison of adult and child is safe and suitable for use. although there are also * infants and toddlers – 28 days to 23 months other information sources. it b chemical ingredient is important that two-way communication between * Route of administration: hospital pharmacy and community pharmacy is a topical encouraged. (NPPG) (www. * DIAL (Drug Information Advisory Line) – a national unit providing paediatric medicines Although.uk. as the formulation given (higher risk associated with calculation may affect the bioavailability of the drug. for example: * children – 2 to 11 years * adolescents – 12 to 18 years. Fax: (0151) are specifically designed for paediatric use. It is. It must not be assumed that weights – age-related differences in drug handling as the formula originated from a hospital (or other and drug sensitivity prevent this from being accurate.nppg.org. icines are licensed for use solely in adults and are dial. The When using formulae from sources such as the local drug-handling capabilities of the body change hospital. If the medicine is used to treat the latter con. Most ‘one-off’ extemporaneous preparations orig. errors) .org. recommended therefore.org). medicinal agents licensed for adults Medicines Information Services can be found in are frequently used in children in a so-called ‘off-label’ the current edition of the British National manner. another. the local hospital weeks’ gestation from where the formula originated is often the next * term newborn infant neonate – 0 to 27 days best source of information. imperative that formulations should remain doses for paediatric use may be given in monographs unchanged. be licensed for use in a particular paediatric condition * The Royal College of Paediatrics and Child and then subsequently found to be efficacious in Health (RCPCH) (www. However. Web: www. The use of body surface area is a more accurate way to Formulation considerations for determine doses in individual paediatric situations. Alternatively. as highlighted above. healthcare environment) it is safe for the patient.org. children has not been examined and the product is * The current edition of the British National therefore not licensed. it must be remembered that the compounder markedly from birth to adulthood.uk/). the child should not be considered to be a ‘mini adult’.bnfc. In the primary care situation. This b parenteral – intramuscular (painful. extemporaneous preparations for children These principles also apply in geriatric medicine. is particularly important in the case of extemporane. some medicines information.rcpch.uk/). usually tablets or cap- contact details for Regional and District sules.ac. e-mail: info@dial. In these situations. therefore less acceptable) or intravenous ously prepared medicines. Dose checking for paediatric preparations can be Other terms that may be used instead of age extremely difficult and may involve a lengthy search include the following recommended by the Royal for information. many med- 220 3885. When considering formulations for children. therefore routinely made in formulations that are most * Drug information centres and local hospitals – appropriate for use by adults. Since current healthcare strategies a adult dosage form (tablet or capsule) are to shift therapy from secondary to primary care. corticosteroids may be absorbed systemically and ability for conversion of a tablet or capsule to this produce significant adrenal suppression. of gastric acid is reduced and therefore gastric pH is not comparable to adult levels. Obvious exceptions to suit. Types of oral formulation to consider are: for example. Other of the factors that influence drug therapy in children. In addition. These are usually ones with narrow therapeutic indices. or combining the contents of the required number of when occlusive coverings are applied. with a diluent such as Starch BP or Lactose BP. diazepam solution stops seizures rapidly and can be Absorption administered rectally in an emergency. This can capsules with a suitable diluent. . where the When checking paediatric doses we need to be aware absorption from the rectum can be erratic. state. there is greater potential for Smaller or tailored doses of drugs that are available in systemic absorption and resultant side effects after tablet or capsule form can be made by crushing the topical application in the neonate. metab. sustained release adults. However. for example. required than would otherwise be expected. preparations need to be used with caution in larger doses of water-soluble drugs are often young children. the stratum corneum of the neonate is Powders thinner. distribution. dosage form include: * Rectal absorption – Absorption via the rectal * enteric coated tablets or other coated tablets route can be erratic and variable in children and is * sustained release (SR) or modified release (MR) not one favoured by parents. or when application is to broken or inflamed skin. taste and texture * Topical absorption – Neonates have a greater c stability. increased absorption of acid-labile * powders medicines such as penicillin because of reduced * segments from tablets (uniformity of dose is drug breakdown. This is required number of tablets in a mortar and mixing particularly so when potent agents are applied. Topical drug in aqueous solution. In young Distribution infants the gastric emptying time may be prolonged. or slowed or reduced absorption limited by accuracy of tablet splitting) of acidic medicines such as phenytoin or * liquid phenobarbital because of changes in ionisation a formulation – solution. Factors influencing drug therapy in paediatric where predicting the absorption is important. Specialised formulation issues | 209 c rectal – acceptability to the parent or patient Oral absorption is also affected by increased (if child rather than infant) gastric pH. but by six months of age it will be * Increased total body water – During infancy. the approaching adult rates. suspension. Certain drugs should the production of a liquid formulation. b palatability. Therefore. absorption through the rectal mucosa and their olism and excretion. For example. This can cause. Before the age of two years the output d oral. etc. rapid onset of action. on a dose to body weight basis. neurotoxicity and death to use if there are issues concerning the stability of a following hexochlorophene absorption. it is useful tablets or capsules if the child is vomiting or is disinclined or unable * dispersible tablets which may lend themselves to to take medicine orally. Therefore. drugs are employed rectally because of the rapid These factors include absorption. Although the extent of percentage body weight contributed by water is drug absorption is not normally affected. This is a good method cause. * Oral absorption – This can be affected by variable gastric and intestinal transit times. for patients example in the case of theophylline. never be administered to children rectally. body surface area-to-weight ratio than adults. Therefore. the rate appreciably higher than in older children and of absorption can be. Consequently. for drugs with a wide therapeutic index. significant competition cosides. When checking geriatric doses. children may require more frequent Just as there are differences in doses recommended for dosing or higher doses on a mg/kg basis. requirements and renal function better than for example where gentamicin is used to treat weight-based dosing. 65s). any be taken into consideration: . have longer half-lives. This is because the would not normally penetrate the central nervous surface area reflects cardiac output. glucuronidation are reduced in the neonate. drugs that undergo glucuronidation. phenytoin. such as chloramphenicol. geriatric patients Therefore. dose reduction. children need higher population but receive 39% of the prescribed drugs doses of anticonvulsants per kilogram body (twice as many as younger people). Paracetamol is metabolised by sulphation the relationship between ideal body weight. This can be used to advantage. Drugs such as elderly population (generally accepted as the over- carbamazepine. * Age – Doses based on age range are mainly used Similarly. phenobarbital. the following need to ing adult values at 6–12 months of age. ethosuximide. with tables to guide percentage Oxidised drugs. digoxin and penicillins. This is because the latter metabolic route cialist paediatric formularies are available.210 | Pharmaceutical forms and their preparation * Decreased plasma protein binding – Because drugs that will be excreted by this route will require neonates have relatively high levels of bilirubin. For example.1) and a number of spe- in adults. It can also be difficult to ascertain Enzyme systems mature at different times and the height of a child accurately. height and in the neonate. lives and tend to accumulate in neonates. this central sepsis and meningitis in neonates. reach. rather than by glucuronidation as body surface area (Table 13. Therefore. This is especially true of the aminogly- which protein binds. method is of limited use as the surface area can increase by 1–2% per day in a young child and Metabolism therefore any dose would need frequent * readjustment. Hepatic children because of the pharmacokinetic differences microsomal oxidation is more rapid in children between adults and children. * Altered metabolic pathways may exist for some The British National Formulary gives guidance on drugs. weight than adults. In practice. Factors influencing drug therapy in geriatric Excretion patients Renal excretory capacity is reduced in neonates. fluid system may do so. but * Weight – Weight-based calculations are the most demethylation and sulphation are little affected. especially in small may be absent at birth. all of between the bilirubin and highly protein-bound which have prolonged half-lives during the first week drugs can occur. * Blood–brain barrier – The blood–brain barrier is * Body surface area – This is the most accurate way poorly developed in neonates and drugs that to calculate a dose for a child. such as lidocaine. An awareness of the differences in drug handling phenytoin and theophylline all have significantly presented by the elderly is significant if you consider shorter half-lives in children than they do in that the over-65s constitute about 18% of the UK adults. * Metabolic rate increases dramatically in children Extemporaneous formulations for and in some cases is greater than in adults. phenobarbital. furosemide and indometacin are appreciably less Dose calculations protein bound in a neonate than in an adult. of life. have prolonged half- National Formulary. This There are a number of factors that need to be taken results in higher levels of free drug and therefore it into consideration when calculating a dose for a pae- may be necessary to give larger loading doses of diatric patient: highly protein-bound drugs in neonates. takes several months to become fully mature. cephalosporins. commonly used. this also applies to the (1–10 years) than in adults. calculations being available in the British phenytoin and diazepam. Hepatic oxidation and children. however. e. compare warfarin). then it should be safe. body mass and consequently there tends to be an increased volume of distribution of The dose check lipophilic drugs (e.74 7 years 23 51 120 47 0.2 9 55 22 0.7 17 67 26 0. The with age.5 7. Is the formula safe? b Decrease in body water which results in a decreased volume of distribution of water.65 5 years 18 40 108 42 0. impaired.g.6 12 59 23 0. It is more likely to change because easiest way to check the formula is to find a similar of an existing disease state. water-soluble drugs. a Body fat – Geriatric patients tend to have lean should be given in reduced dosages. If the c Protein binding does not significantly change formula is unofficial. or find . who may need reduced dosage according to their clinical condition. the effect of food and any usually declines with age. benzodiazepines).41 1 year 10 22 76 30 0. ingredients must be checked individually (i. official product and then look at the ingredients that * Metabolism – Hepatic metabolism is affected by differ and determine whether they are within safe lim- the reduced liver blood flow that occurs with age. its (e. drugs that undergo extensive first-pass If there is no similar official formula then all the metabolism (e. propranolol. Specialised formulation issues | 211 Table 13. then it must be checked. 57th edition) Age Ideal body weight Height Body surface kg lb cm inch m2 Full-term neonatea 3.30 Adult Male 68 150 173 68 1. especially those * Distribution with a narrow therapeutic index (e. If the formula is official.49 3 years 15 33 94 37 0. * Absorption – Age differences are of little clinical * Excretion – Renal excretion is heavily reliant on value but consideration must be given to the rate the glomerular filtration rate of the kidney.80 Female 56 123 163 64 1. If renal function is disease of the small intestine.24 1 montha 4. Products for internal route of administration soluble drugs. which of gastric emptying.27 3 monthsa 5.g.88 12 years 39 86 148 58 1.g. verapamil. the contents of products with similar uses.g.7 50 20 0. digoxin). compare the amounts in other products with This means that there is reduced clearance of similar uses).1 Relationship between ideal body weight and body surface area for children of different ages and adults (adapted from the British National Formulary.60 a The figures relate to full-term and not preterm infants.33 6 months 7. where the accepted difficult to wet with water. Physical whatever dose is suggested. always take into consideration that. Remember that underdosing can be as serious as overdosing. If two 5 mL spoonfuls are to be given three times a When formulating extemporaneous products care day. 10 mL. Too low a con. two would be the dose. * increased likelihood of side effects associated with centration could render the product ineffective.g. A classic example of an should be queried with the prescriber. Incompatibilities can be ther- the dose of an oral liquid is specified as 5 mL or apeutic. the medication * reduced patient compliance because of increased Is the dose safe? side effects (e. * Oils and water. This includes extemporaneously prepared therapeutic incompati- doses/quantities that appear to be lower than those in bility would be the formulation of a cough medicine the literature as well as those that appear to be higher. Once again the . This problem is solved dosage measure is a 5 mL spoon or an oral syringe. Underdosing can result in: Insolubility * reduced or no therapeutic effect * Liquid preparations containing an indiffusible * loss of control of a medical condition with powder such as chalk require a suspending agent possible progression of the disease or thickening agent to ensure an even dose * symptoms suffered unnecessarily delivery.212 | Pharmaceutical forms and their preparation information on safe dose ranges for each individual Overdosing can result in: ingredient). administer/measure 3. This can be overcome using ing out a dose that would mean a patient had to emulsifying agents. 10 mL would be the dose). containing both an expectorant and a cough sup- When querying a dose it is also advisable to have a pressant. * possible fatal consequences In addition it should be borne in mind that too high a * possibility of hospital admission. must be taken to avoid incompatibilities between * Is the dose frequency safe? In older references the ingredients that might result in the production of an dose frequency may not be specified. diluted with an aqueous vehicle. This is normally the responsibility of the prescriber and is more akin to the drug interactions we are aware Dose checks that do not concur with the literature of in modern dispensing. it must be suitable for Immiscibility administration to the patient in the given pharmaceu- tical form. * discontinuation of treatment by the patient as they * Resinous tinctures produce precipitates when perceive no benefit. the dose regimen would be 5 mL or 10 mL Therapeutic three or four times daily by convention.g.642 mL of a solution to obtain * Insoluble powders that are difficult to wet (e. however. suggested alternative to offer that would be accept- able. which can be concentration of an active ingredient could potentially inconvenient to the patient and have high cost cause serious damage to the skin and also introduce implications the possibility of systemic absorption. administered at one time (e.g. Note that if unsatisfactory product. For example. by the addition of wetting agents. drowsiness) Products for internal administration * new medical problems being encountered that * What is the dose? The dose is the quantity to be have been precipitated by the overdose. it would be of little use work. if two tablets are to Incompatibilities be taken three times a day. physical or chemical. the appropriate dose as this would not be measurable sulphur) and some corticosteroids that are in the primary care environment. * adverse effects to patient that may be temporary Products for external application or long term Checks should be used similar to those outlined above. although not recommended by the manufacturer. These extemporaneous dispensing seen in the primary care include: setting. One * ease of administration leading to better patient problem is that dithranol is subject to oxidative compliance degradation. there may be a problem in that dilution of the product does not nec- Chemical essarily result in a proportional dilution of potency. fatal overdose in the overly concentrated last few Dilution of a topical steroid allows the prescriber doses. sist of formulae ranging from the preparation of eczema and other skin conditions. including combining different proprietary coal tar and therefore gloves must be worn when brands within the same formulation. observed clinical response. In addition. Specialised formulation issues | 213 addition of a suspending agent will ensure even Dilutions of topical steroids have been popular for dose delivery. such as wearing active form of the drug into a less active form goggles. Synalar dosing owing to insufficient shaking of a and Synalar 1 in 10 Dilution and Synalar 1 in 4 suspension. which will con- * Coal Tar BP – Used in the treatment of psoriasis. either precautions must be taken when preparing rendering them virtually inactive or converting the extemporaneous formulations. Failure to do this can result in possibly Dilution). solvent is used to dissolve the powder initially. formulation In addition to the dilution of topical steroid Extemporaneous formulation of products for topical a number of other ingredients form part of the application is probably the most common form of standard formulary in many specialist units. preparations the addition of ascorbic acid or oxalic acid as an antioxidant has been found to be Problems that may be encountered include: helpful. where it * two or more active ingredients combined in one has the advantage of penetrating the psoriatic preparation may have a synergistic effect lesions more speedily than normal skin. some time and have even led to manufacturers produc- * A potent insoluble drug may be replaced with a ing ready-made dilutions of their products (e. and therefore an antioxidant added * may lead to reduction in course of treatment to the formulation would be an advantage. gloves and a mask. * Dithranol BP – Used to treat psoriasis. certain extent by the introduction of diluent direc- tories. many specialist hospital units have their own dermatological formulary. * unpredictable interactions Dithranol is extremely irritant and therefore * decreased stability of the active ingredients. which recommended the diluent to use if dilu- Dermatological extemporaneous tion. because of 1 and 2 above Salicylic acid does this in ointment formulations * ability to prepare a formulation when no suitable/ such as dithranol in Lassar’s paste. This issue was addressed to a a harmful or dangerous product. In When practitioners regularly made their own formu. addition there is a risk of incompatibility between the lae there was always concern that a combination of complex proprietary formulations and the simple prescribed substances could result in the formation of bases used for dilution. it may be better to replace an to change the strength of product based on the insoluble alkaloid with a soluble alkaloidal salt. Ointments creams and ointments from first principles to diluting containing coal tar or an alcoholic solution of coal or combining proprietary products.g. In cream equivalent proprietary preparation is available. For example. concern over the potential carcinogenic effects of ducts. There is Advantages of extemporaneously prepared pro. was insisted upon. . include: preparing a product. However. soluble salt in some cases to prevent uneven Betnovate and Betnovate-RD preparations. should be prepared without heating. As the powder is so * reduced activity of any preservative present as a irritant it is advised that during trituration a result of varying combinations of products. Soft Paraffin BP would not be a suitable base for a preparation intended for use as a pomade or Bases regularly used for extemporaneous prepara- shampoo) tion of ointments/creams or the dilution of ointments/ * any solubility characteristics of the active creams include: ingredient * Aqueous Cream BP * cosmetic and general acceptability to the * Buffered Cream BP patient * Cetomacrogol Cream (Formula A) BP * the safety and stability of the final preparation. strength usually employed is 10–50%. collodion paints for warts and corns 10–12%. In ointment preparations the BP. and the choice of vehicle is of importance in dandruff. The strengths depending on the condition treated. White and corns 20–50%. carrier. and plasters for the destruction of warts * suitability for intended use (for example. * Emulsifying Ointment BP * Ichthammol BP – This has slight bacteriostatic * Unguentum Merck properties and is used topically for a wide range of * Yellow Soft Paraffin BP and White Soft Paraffin skin disorders. eczema or psoriasis usually contain terms of: 1–5%. . vehicle itself has a greater effect than just a placebo or Ointments for the treatment of chronic ulcers.214 | Pharmaceutical forms and their preparation Liquid Paraffin BP or chloroform has been used * Cetomacrogol Cream (Formula B) BP successfully. Both the vehicle (base) and the active ingredients * Salicylic Acid BP – This is used in varying are important in the treatment of skin conditions. Pharmaceutical Press. Williams & Wilkins. history behind the formulations. the following text will be of use to 4th edn. Aulton M E (ed) (1990) Pharmaceutical stand pharmaceutical calculations. ceutical Calculations. those compounders wishing to find out more about the Baltimore. Churchill Livingstone. CRC Press. London. Florida. USA. Jasti B R (ed) (2005) Theory and Practice of Contemporary Pharmaceutics. compounders wishing to practise and further under- Collett D M. Quinn M E (ed) (2009) Handbook of Pharmaceutical Excipients. USA. Aulton M E (ed) (2007) Aulton’s Pharmaceutics.Further reading It is beyond the scope of this book to go into detail on The following text will be useful to student phar- the science behind the different formulations described macists and pharmacy technicians who wish to revise in the various chapters. Anderson S (ed) (2005) Making Medicines: A Brief History London. Maryland. Churchill Livingstone. Pharmaceutical Press. USA. Ghosh T K. . Smith I. Edinburgh. London. Rhodes C T (ed) (2007) Modern Pharmaceutics. Pharmaceutical Press. In addition. Compounding and Dispensing. Belcher D (2008) FASTtrack: Pharmaceutical the science behind the formulations. Edinburgh. Thompson J E. Pharmaceutical Press. USA. Lippincott. 3rd edn. Banker G S. Sheskey P Y. New York. the following text would be of interest to Martin A N (2010) Martin’s Physical Pharmacy and Pharma- ceutical Sciences. 6th edn. Florence A T. Davidow L W (2009) A Practical Guide to London. Williams & Wilkins. Smith B (2005) Introduction to Pharma- of Pharmacy. Finally. Maryland. Practice. of use to compounders who wish to learn more about Langley C A. Contemporary Pharmacy Practice. 6th edn. of Pharmacy and Pharmaceuticals. Baltimore. Rowe RC. London. The texts listed below will be the concepts covered in this book. Attwood D (2006) Physicochemical Principles Rees J A. Marcel Dekker. Pharmaceutical Press. 3rd edn. Lippincott. . PART 3 Product formulae . . this part of the (Mistura Carminativa) 234 book contains a selection of extemporaneous formu- lae. Benzyl Benzoate Application BP (Benzyl Benz Applic) 249 A Buffered Cream BP (Cremor Normalis) 226 Alkaline Gentian Mixture BP 236 Alkaline Gentian Mixture with C Phenobarbitone BPC (Mistura Gentianae Calamine and Coal Tar Ointment BP 253 Alkalina cum Phenobarbitono) 236 Calamine and Coal Tar Ointment BP also known Aluminium Hydroxide and Belladonna as Compound Calamine Ointment BP Mixture BPC 235 (Unguentum Calaminae et Picis Carbonis) 254 Ammonia and Ipecacuanha Mixture BP Calamine Cream Aqueous BPC (Mistura Expectorans) 235 (Cremor Calaminae Aquosus) 226 Ammoniated Potassium Iodide Mixture BPC Calamine Lotion BP (Calam Lot) 250 (Mistura Potassii Iodide Ammoniata) 238 Calamine Lotion Oily BP Ammoniated Rhubarb and Soda Mixture (Lotio Calamine Oleosa) 250 BPC (Mistura Rhei Ammoniate et Sodae) 238 Calamine Ointment BP (Unguentum Calaminae) 253 Ammonium Chloride and Morphine Cascara and Belladonna Mixture BPC Mixture BP (Mistura Tussi Sedativa) 241 (Mistura Cascarae et Belladonnae) 235 . (Mistura Belladonna pro Infantibus) 233 uct formulae contained in all three parts of the book. in alphabetical order. These are a mixture of old formulae that are now B rarely used but which still have a place in therapeutics Belladonna and Ephedrine Mixture along with some formulae that have been derived from Paediatric BPC (Mistura Belladonnae et old texts. to compound (Mistura Ammonii Chloridi) 240 extemporaneous products for patients. Belladonna Tincture BP (Tinctura Belladonnae) 31 The source of each formula is included with its entry. Ephedrinae pro Infantibus) 241 Belladonna and Ipecacuanha Mixture Formulae contents Paediatric BPC 241 Belladonna Mixture Paediatric BPC The following index lists. Aromatic Magnesium Carbonate Mixture BPC lation for an extemporaneous product. espe. Ammonium Chloride Mixture BP cially within a primary care setting. (Tinctura Carminative) 30 To assist the compounder in their choice of formu.Preface As a result of recent changes in pharmaceutical prac. prod. This has Aqueous Cream BP (Cremor Cerae Aquos resulted in a comparable decline in the inclusion of also known as Simple Cream) 226 extemporaneous formulae in modern official text Aromatic Cardamom Tincture BP books. Ammonium Chloride Mixture BP 240 tice it is becoming less common for pharmacists. Cocaine and Chlorpromazine Composita pro Infantibus) 235 Elixir BPC 244 Compound Camphorated Opium Mixture BPC Dimethicone Cream BPC (Cremor Dimethiconi) 225 (Mistura Opii Camphorata Composita) 238 Dithranol Paste BP 180 Compound Cardamom Tincture BP Double Strength Chloroform Water BP 33 (Tinctura Cardamomi Composite) 31 Compound Gentian Tincture BP (Tinctura Gentianae Composite) 31 E Compound infusion of horseradish Effervescent Powder Compound BPC (Infusum Armoraciae Compositum) 23 (Pulvis Effervescens Compositus also Compound Magnesium Trisilicate known as Seidlitz Powder) 257 Oral Powder BP 203 Emulsifying Ointment BP (Ung Emulsif) 255 .220 | Product formulae Cetomacrogol Cream BP 220 Compound Rhubarb Mixture BPC Cetomacrogol Emulsifying Ointment BP (Mistura Rhei Composita) 238 also called Non-ionic Emulsifying Ointment BP Compound Rhubarb Mixture Paediatric BPC (Unguentum Cetomacrogolis Emulsificans) 254 (Mistura Rhei Composita pro Infantibus) 238 Cetrimide Cream BP 225 Compound Sodium Chloride and Dextrose Oral Cetrimide Cream BP (Cremor Cetrimidi) 225 Powder BP (per powder) 257 Cetrimide Emulsifying Ointment BP Compound Sodium Chloride Mixture BPC (Unguentum Cetrimidi Emulsificans) 255 (Mistura Sodii Chloridi Composita) 239 Chalk Mixture Paediatric BP 123 Compound Sodium Chloride Mouthwash BP Chalk with Opium Mixture Aromatic BPC (Collutorium Sodii Chloridi Compositum) 259 (Mistura Cretae Aromatica cum Opio) 241 Compound Tolu Linctus Paediatric BPC Chloral Elixir Paediatric BPC (Linctus Tolutanus Compositus pro Infantibus) 247 (Elixir Chloralis pro Infantibus) 243 Compound Zinc Paste BP 255 Chloral Mixture BP (Mist Chloral) 241 Compound Zinc Paste BP (Co Zinc Paste) 255 Chlorhexidine Cream BPC (Cremor Concentrated Anise Water BP Chlorhexidinae) 227 (Aqua Anisi Concentrata) 34 Chlorhexidine Dusting Powder BPC 229 Concentrated Camphor Water BP Chloroform Water BP 106 (Aqua Camphorae Concentrata) 34 Chloroxylenol Solution BP Concentrated Chloroform Water BPC 1959 33 (Liquor Chloroxylenolis) 260 Concentrated Chloroform Water BPC 1959 Clioquinol Cream BPC 227 (Aqua Chloroformi Concentrata) 33 Coal Tar Paste BPC (Pasta Picis Carbonis) 255 Concentrated Compound Gentian Infusion BP Codeine Linctus BPC (Linctus Codeinae) 243 (Infusum Gentianae Compositum Codeine Linctus Paediatric BPC 244 Concentratum) 25 Colchicum and Sodium Salicylate Mixture BPC Copper and Zinc Sulphates Lotion BPC (Mistura Colchici et Sodii Salicylate) 236 (Dalibour Water) 250 Compound Aluminium Paste BPC (also known as Baltimore Paste) 166 Compound Benzoic Acid Ointment BP D (Whitfield’s Ointment) 253 Decoction of Chondrus BPC Compound Bismuth Subgallate Suppositories BP 191 (Decoctum Chondri) 20 Compound Calamine Application BPC Diamorphine and Cocaine Elixir BPC 244 (Applicatio Calaminae Composita) 251 Diamorphine Linctus BPC Compound Calcium Carbonate Mixture (Linctus Diamorphinae) 245 Paediatric BPC (Mistura Calcii Carbonatis Diamorphine. Preface | 221 Ephedrine Elixir BPC (Elixir Ephedrinae) 244 Infusion of Catechu BP (Infusum Catechu) 23 Ephedrine Nasal Drops BPC Infusion of Valerian BPC (Infusum Valerianae) 23 (Naristillae Ephedrinae) 259 Ipecacuanha and Ammonia Mixture Paediatric Extract of Cannabis BPC (Extractum Cannabis) 21 BPC (Mistura Ipecacuanhae et Ammoniae pro Infantibus) 237 F Ipecacuanha and Morphine Mixture BPC Ferric Ammonium Citrate Mixture BPC (Mistura Tussi Nigra) 242 (Mist Ferr et Ammon Cit) 242 Ipecacuanha and Squill Linctus Paediatric BPC Ferric Ammonium Citrate Mixture Paediatric (Mist Tussi Rubra pro Inf) 236 BPC (Mistura Ferri et Ammonii Citratis Ipecacuanha Mixture Paediatric BPC pro Infantibus) 242 (Mistura Ipecacuanha pro Infantibus) 237 Ferrous Sulphate Mixture BPC Isoniazid Elixir BPC 245 (Mistura Ferri Sulphatis) 242 Ferrous Sulphate Mixture Paediatric BP K (Mistura Ferri Sulphatis pro Infantibus) 235 Kaolin and Morphine Mixture BP Fresh Acid Infusion of Rose BPC (Mistura Kaolini Sedativa) 243 (Infusum Rosae Acidum Recens) 24 Kaolin Mixture BP (Mistura Kaolini) 240 Kaolin Mixture Paediatric BP G (Mistura Kaolini pro Infantibus) 240 Gelsemium and Hyoscyamus Mixture Compound BPC (Mistura Gelsemii et Hyoscyami L Composita) 236 Gentian Acid Mixture BPC Linctus Squill Opiate BPC (also known (Mistura Gentianae Acida) 239 as Gees Linctus) (Linctus Scillae Opiatus) 246 Gentian Acid Mixture with Nux Liquid Extract of Hamamelis BPC Vomica BPC (Mistura Gentianae Acida (Extractum Hamamelis Liquidum) 21 cum Nuce Vomica) 236 Liquid Extract of Liquorice BP Gentian Alkaline Mixture BP (Extractum Glycyrrhizae Liquidum) 22 (Mistura Gentianae cum Soda) 239 Liquid Paraffin Emulsion BP 148 Gentian Alkaline Mixture with Nux Lobelia and Stramonium Mixture Vomica BPC (Mistura Gentianae Alkalina Compound BPC (Mistura Lobeliae cum Nuce Vomica) 236 et Stramonii Composta) 237 Gentian and Rhubarb Mixture BPC (Mistura Gentianae cum Rheo) 233 M Glycerite of Tar (Glyceritum Picis Liquieae) 22 Magnesium Carbonate Mixture BPC Glycerol Suppositories BP 187 (Mistura Magnesii Carbonatis) 233 Magnesium Sulphate Mixture BPC H (Mistura Alba) 234 Hexachlorophane Dusting Powder BPC 229 Magnesium Trisilicate and Belladonna Hydrocortisone Cream BPC Mixture BPC (Mist Mag Trisil et Bellad) 243 (Cremor Hydrocortisoni) 227 Magnesium Trisilicate Mixture BP 240 Magnesium Trisilicate Mixture BP I (Mistura Magnesii Trisilicatis) 240 Ichthammol Ointment BP Magnesium Trisilicate Powder Compound BP (Unguentum Ichthammolis) 255 (Pulvis Magnesii Trisilicatis Compositus) 257 . 222 | Product formulae Menthol and Eucalyptus Inhalation BP 259 Salicylic Acid Lotion BP (Lotio Acidi Salicylici) 250 Menthol and Eucalyptus Inhalation BP Salicylic Acid Ointment BP (Ung Acid Salicyl) 255 (Vapor Mentholis et Eucalypti) 259 Saline Mixture BPC (Mistura Diaphoretica) 233 Methadone Linctus BPC (Linctus Methadoni) 246 Senega Infusion Concentrated BPC Methyl Salicylate Ointment BP (Infusum Senegae Concentatum) 25 (Unguentum Methylis Salicylatis) 255 Simple Linctus BPC (Linctus Simplex) 246 Morphine and Cocaine Elixir BPC 244 Simple Linctus Paediatric BPC (Linctus Simplex pro Infantibus) 246 N Simple Ointment BP 254 Simple Ointment BP (Ung Simp) 254 Nux Vomica Mixture Acid BPC Soap Liniment BPC (Linimentum Saponis (Mistura Nucis Vomicae Acida) 237 also known as Opodeldoc) 249 Nux Vomica Mixture Alkaline BPC Sodium Bicarbonate Ear Drops BP (Mistura Nucis Vomicae Alkalina) 237 (Auristillae Sodii Bicarbonatis) 259 Sodium Bicarbonate Paediatric Mixture BPC O (Mist Sod Bicarb pro Inf) 243 Oral Rehydration Salts Formula A BP 257 Sodium Chloride Compound Mouthwash BP 109 Orange Peel Infusion Concentrated BPC Sodium Citrate Mixture BPC (Infusum Aurantii Concentratum) 24 (Mistura Sodium Citratis) 239 Oxymel BPC 26 Sodium Salicylate Mixture BPC (Mistura Sodii Salicylatis) 239 P Sodium Salicylate Mixture Strong BP Paediatric Chalk Mixture BP (Mistura Sodii Salicylatis Fortis) 240 (Mistura Cretae pro Infantibus) 239 Squill Linctus Opiate Paediatric BPC Paediatric Opiate Ipecacuanha Mixture BPC 237 (Linctus Scillae Opiatus pro Infantibus) 247 Paracetamol Elixir Paediatric BPC Squill Oxymel BPC 27 (Elixir Paracetamolis pro Infantibus) 245 Squill Vinegar BPC (Acetum Scillae) 32 Paraffin Ointment BP 78 Stramonium and Potassium Iodide Mixture BPC Phenobarbitone Elixir BPC (Mistura Stramonii et Potassii Iodidi) 239 (Elixir Phenobarbitoni) 245 Sulphur Lotion Compound BPC Pholcodine Linctus BPC (Linctus Pholcodinae) 246 (Lotio Sulph Co) 250 Pholcodine Linctus Strong BPC Sulphur Ointment BP 254 (Linctus Pholcodinae Fortis) 246 Potassium Citrate and Hyoscyamus Mixture BPC (Mistura Potassii Citratis et Hyoscyamus) 238 T Potassium Citrate Mixture BP Talc Dusting Powder BP (Conspersus Talci) 229 (Mistura Potassii Citratis) 234 W Q White Liniment BP 251 Quillaia Tincture BP (Tinctura Quillaiae) 30 White Liniment BPC (Linimentum Album) 251 S Salicylic Acid and Sulphur Cream BP Z (Cremor Acidi Salicylici et Sulphuris) 226 Zinc and Coal Tar Paste BP 254 Salicylic Acid and Sulphur Cream BP 1980 150 Zinc and Coal Tar Paste BP (also known as Salicylic Acid and Sulphur Ointment BPC White’s Tar Paste) 166 (Ung Acid Salicyl et Sulph) 255 Zinc and Coal Tar Paste BP (White’s Tar Paste) 254 . Preface | 223 Zinc and Ichthammol Cream BP (Cremor Zinc Sulphate and Zinc Chloride Mouthwash Zinci et Ichthammolis) 226 BPC (Collutorium Zinci Sulphatis et Zinc and Salicylic Acid Paste BP (Lassar’s Paste) 254 Zinci Chloridi) 260 Zinc Cream BP 226 Zinc Sulphate Lotion BP (Lotio Rubra) 250 Zinc Gelatin BPC (also known as Unna’s Paste) 167 Zinc. Zinc Ointment BP (Ung Zinc) 255 Amyli et Talci) 229 Zinc Starch and Talc Dusting Powder BPC 229 . Starch and Talc Dusting Zinc Ointment BP 255 Powder BPC (Conspersus Zinci. . 14 Creams Cetrimide Cream BP (Cremor Cetrimidi) 225 Aqueous Cream BP (Cremor Cerae Aquos – also known as Simple Cream) 226 Dimethicone Cream BPC (Cremor Dimethiconi) 225 Zinc Cream BP 226 Salicylic Acid and Sulphur Cream BP (Cremor Acidi Salicylici et Sulphuris) 226 Cetomacrogol Cream BP 227 Zinc and Ichthammol Cream BP (Cremor Zinci Chlorhexidine Cream BPC et Ichthammolis) 226 (Cremor Chlorhexidinae) 227 Calamine Cream Aqueous BPC (Cremor Clioquinol Cream BPC 227 Calaminae Aquosus) 226 Hydrocortisone Cream BPC Buffered Cream BP (Cremor Normalis) 226 (Cremor Hydrocortisoni) 227 Cetrimide Cream BP (Cremor Cetrimidi) Dimethicone Cream BPC (Cremor Dimethiconi) (BP 1988. Use: Used as a barrier cream. . page 657) Ingredients Quantities Ingredients Quantities Liquid Paraffin BP 500 g Liquid Paraffin BP 400 g Cetostearyl Alcohol BP 50 g Dimethicone 350 BP 100 g Cetrimide BP 5g Cetostearyl Alcohol BP 50 g Freshly boiled and cooled purified water 445 g Dose: Apply when required (but do not apply repeatedly). Use: Used as an antiseptic cream. for example for the prevention of napkin rash or pressure sores. page 653) (BPC 1973. Cetrimide BP 5g Chlorocresol BP 1g Freshly boiled and cooled purified water 444 g Dose: Apply when required. Use: Emollient cream used as a base carrier of other active ingredients. page 666) Aqueous Cream BP (Cremor Cerae Aquos – also known as Simple Cream) (BP 1988. page 548) page 652) Ingredients Quantities Ingredients Quantities Aqueous Cream BP 960 g Sodium Phosphate BP 25 g Salicylic Acid BP 20 g Citric Acid BP 5g Sulphur BP 20 g Chlorocresol BP 1g Emulsifying Ointment BP 300 g Dose: Apply twice a day. page 656) Ingredients Quantities Ingredients Quantities Zinc Oxide BP 320 g Calamine BP 40 g Calcium Hydroxide BP 0. page 665) Calaminae Aquosus) (BPC. forms of eczema. Use: Emollient cream used as a base carrier of other active ingredients. Freshly boiled and cooled purified water 669 g Use: Used to treat mild acne. . Zinc and Ichthammol Cream BP (Cremor Zinci et Ichthammolis) (BP 1988. Ichthammol is Phenoxyethanol is used as a preservative. Acidi Salicylici et Sulphuris) (BP 1980. 1973. page 650) Ingredients Quantities Ingredients Quantities Zinc Cream BP 820 g Wool Fat BP 100 g Emulsifying Ointment BP 300 g Ichthammol BP 50 g Phenoxyethanol BP 10 g Cetostearyl Alcohol BP 30 g Freshly boiled and cooled purified water 690 g Dose: Apply twice daily. Earlier formulae milder than coal tar and is used to treat less acute use 0. Use: Used as a mild astringent for the skin and as a Use: Used to relieve itching. Calamine Cream Aqueous BPC (Cremor Zinc Cream BP (BP 1988.226 | Product formulae Salicylic Acid and Sulphur Cream BP (Cremor Buffered Cream BP (Cremor Normalis) (BP 1988. Use: Used to treat psoriasis and eczema. soothing and protective application in eczema.45 g Zinc Oxide BP 30 g Oleic Acid BP 5 mL Arachis Oil BP 300 g Arachis Oil BP 320 mL Emulsifying Wax BP 60 g Wool Fat BP 80 g Freshly boiled and cooled purified water 570 g Freshly boiled and cooled purified water to 1000 g Dose: Apply when required.1% chlorocresol as a preservative. Liquid Paraffin BP. page 658) Formula A Ingredients Quantities Clioquinol BP 30 g Ingredients Quantities Chlorocresol BP 1g Cetomacrogol Emulsifying Ointment BP 300 g Cetomacrogol Emulsifying Ointment BP 300 g Chlorocresol BP 1g Purified water freshly boiled and cooled to 1000 g Purified water freshly boiled and cooled 669 g Caution: Clioquinol may stain clothing or discolour fair hair. Creams | 227 Cetomacrogol Cream BP (BP 1988. White Soft Paraffin BP and Cetomacrogol Emulsifying Ointment BP 300 g Cetomacrogol Emulsifying Wax BP. Hydrocortisone BP or Hydrocortisone 10 g A better product is produced if the Cetomacrogol Emulsifying Acetate BP Ointment BP is replaced by the appropriate quantities of Chlorocresol BP 1g ingredients (i. Chlorhexidine Cream BPC (Cremor Chlorhexidinae) (BPC 1973. see Chapter 18 for formula).e. page 657) Ingredients Quantities Chlorhexidine Gluconate Solution BP 50 mL Cetomacrogol Emulsifying Wax BP 250 g Liquid Paraffin BP 100 g Purified water freshly boiled and cooled to 1000 g Use: Antiseptic cream. Purified water freshly boiled and cooled 689 g Use: Rarely used in its own right as an emollient. .5 g Hydrocortisoni) (BPC 1973. usually Use: Used to treat eczema. used as a diluent for other creams (see NPA diluent directory). Formula B Use: Treat skin infections. page 653) Clioquinol Cream BPC (BPC 1973.8 g Hydrocortisone Cream BPC (Cremor Methyl Hydroxybenzoate BP 1. Ingredients Quantities Cetomacrogol Emulsifying Ointment BP 300 g Benzyl Alcohol BP 15 g Propyl Hydroxybenzoate BP 0. page 659) Purified water freshly boiled and cooled to 1000 g Ingredients Quantities The difference between Formulae A and B is that they contain different preservatives. . Starch and Talc Dusting Powder BPC (Conspersus Zinci. Used to apply to the umbilicus of babies. Talc Dusting Powder BP (Conspersus Talci) page 662) (BP 1988. Amyli et Talci) 229 Hexachlorophane Dusting Powder BPC 229 Talc Dusting Powder BP (Conspersus Talci) 229 Chlorhexidine Dusting Powder BPC (BPC 1973.15 Dusting powders Chlorhexidine Dusting Powder BPC 229 Zinc. Use: A dusting powder to relieve irritation and prevent chafing. Amyli et Talci) (BPC 1973. page 668) Ingredients Quantities Ingredients Quantities Chlorhexidine Hydrochloride BP 5g Purified Talc BP 900 g Maize Starch BP 995 g Maize Starch BP 100 g Use: Disinfectant powder. Use: Absorbent dusting powder. Starch and Talc Dusting Powder BPC (Conspersus Zinci. Hexachlorophane Dusting Powder BPC (BPC 1973. page 663) Zinc. . Ingredients Quantities page 664) Hexachlorophane 3g Ingredients Quantities Zinc Oxide BP 30 g Maize Starch BP 967 g Purified Talc BP 500 g Starch BP 250 g Use: Disinfectant powder with bacteriostatic activity Zinc Oxide BP 250 g against Staphylococcus aureus. . 16 Internal mixtures Saline Mixture BPC (Mistura Diaphoretica) 233 Gentian Alkaline Mixture with Nux Vomica BPC (Mistura Gentianae Alkalina cum Nuce Vomica) 236 Belladonna Mixture Paediatric BPC (Mistura Belladonna pro Infantibus) 233 Alkaline Gentian Mixture with Phenobarbitone BPC (Mistura Gentianae Alkalina cum Phenobarbitono) 236 Gentian and Rhubarb Mixture BPC (Mistura Gentianae cum Rheo) 233 Ipecacuanha and Squill Linctus Paediatric BPC (Mist Tussi Rubra pro Inf) 236 Magnesium Carbonate Mixture BPC (Mistura Magnesii Carbonatis) 233 Ipecacuanha Mixture Paediatric BPC (Mistura Ipecacuanha pro Infantibus) 237 Aromatic Magnesium Carbonate Mixture BPC (Mistura Carminativa) 234 Paediatric Opiate Ipecacuanha Mixture BPC 237 Magnesium Sulphate Mixture BPC (Mistura Alba) 234 Ipecacuanha and Ammonia Mixture Paediatric BPC (Mistura Ipecacuanhae et Ammoniae Potassium Citrate Mixture BP pro Infantibus) 237 (Mistura Potassii Citratis) 234 Lobelia and Stramonium Mixture Compound BPC Paediatric Chalk Mixture BP (Mistura Cretae (Mistura Lobeliae et Stramonii Composta) 237 pro Infantibus) 234 Nux Vomica Mixture Acid BPC (Mistura Nucis Ammonia and Ipecacuanha Mixture BP (Mistura Vomicae Acida) 237 Expectorans) 235 Nux Vomica Mixture Alkaline BPC (Mistura Nucis Ferrous Sulphate Mixture Paediatric BP Vomicae Alkalina) 237 (Mistura Ferri Sulphatis pro Infantibus) 235 Compound Camphorated Opium Mixture BPC Aluminium Hydroxide and Belladonna (Mistura Opii Camphorata Composita) 238 Mixture BPC 235 Potassium Citrate and Hyoscyamus Mixture BPC Compound Calcium Carbonate Mixture (Mistura Potassii Citratis et Hyoscyamus) 238 Paediatric BPC 235 Ammoniated Potassium Iodide Mixture BPC Cascara and Belladonna Mixture BPC (Mistura Potassii Iodide Ammoniata) 238 (Mistura Cascarae et Belladonnae) 235 Compound Rhubarb Mixture BPC Colchicum and Sodium Salicylate Mixture BPC (Mistura Rhei Composita) 238 (Mistura Colchici et Sodii Salicylate) 236 Compound Rhubarb Mixture Paediatric BPC Gelsemium and Hyoscyamus Mixture Compound (Mistura Rhei Composita pro Infantibus) 238 BPC (Mistura Gelsemii et Hyoscyami Composita) 236 Ammoniated Rhubarb and Soda Mixture BPC Gentian Acid Mixture with Nux Vomica BPC (Mistura Rhei Ammoniate et Sodae) 238 (Mistura Gentianae Acida cum Nuce Vomica) 236 . 232 | Product formulae Compound Sodium Chloride Mixture BPC Ipecacuanha and Morphine Mixture BPC (Mistura Sodii Chloridi Composita) 239 (Mistura Tussi Nigra) 242 Sodium Citrate Mixture BPC Kaolin and Morphine Mixture BP (Mistura Sodium Citratis) 239 (Mistura Kaolini Sedativa) 243 Sodium Salicylate Mixture BPC Magnesium Trisilicate and Belladonna Mixture BPC (Mistura Sodii Salicylatis) 239 (Mist Mag Trisil et Bellad) 243 Stramonium and Potassium Iodide Mixture BPC Sodium Bicarbonate Paediatric Mixture BPC (Mistura Stramonii et Potassii Iodidi) 239 (Mist Sod Bicarb pro Inf) 243 Gentian Alkaline Mixture BP Chloral Elixir Paediatric BPC (Elixir Chloralis (Mistura Gentianae cum Soda) 239 pro Infantibus) 243 Gentian Acid Mixture BPC Codeine Linctus BPC (Linctus Codeinae) 243 (Mistura Gentianae Acida) 239 Codeine Linctus Paediatric BPC 244 Magnesium Trisilicate Mixture BP (Mistura Magnesii Trisilicatis) 240 Diamorphine and Cocaine Elixir BPC 244 Sodium Salicylate Mixture Strong BP Diamorphine. Cocaine and Chlorpromazine (Mistura Sodii Salicylatis Fortis) 240 Elixir BPC 244 Ammonium Chloride Mixture BP Morphine and Cocaine Elixir BPC 244 (Mistura Ammonii Chloridi) 240 Ephedrine Elixir BPC (Elixir Ephedrinae) 244 Kaolin Mixture BP Paracetamol Elixir Paediatric BPC (Mistura Kaolini) 240 (Elixir Paracetamolis pro Infantibus) 245 Kaolin Mixture Paediatric BP Isoniazid Elixir BPC 245 (Mistura Kaolini pro Infantibus) 240 Phenobarbitone Elixir BPC (Elixir Phenobarbitoni) 245 Belladonna and Ephedrine Mixture Paediatric BPC (Mistura Belladonnae et Ephedrinae Diamorphine Linctus BPC (Linctus Diamorphinae) 245 pro Infantibus) 241 Methadone Linctus BPC (Linctus Methadoni) 246 Belladonna and Ipecacuanha Mixture Pholcodine Linctus Strong BPC Paediatric BPC 241 (Linctus Pholcodinae Fortis) 246 Ammonium Chloride and Morphine Mixture BP Pholcodine Linctus BPC (Linctus Pholcodinae) 246 (Mistura Tussi Sedativa) 241 Simple Linctus BPC (Linctus Simplex) 246 Chalk with Opium Mixture Aromatic BPC (Mistura Cretae Aromatica cum Opio) 241 Simple Linctus Paediatric BPC (Linctus Simplex pro Infantibus) 246 Chloral Mixture BP (Mist Chloral) 241 Linctus Squill Opiate BPC (also known Ferric Ammonium Citrate Mixture BPC as Gees Linctus) (Linctus Scillae Opiatus) 246 (Mist Ferr et Ammon Cit) 242 Squill Linctus Opiate Paediatric BPC Ferric Ammonium Citrate Mixture Paediatric BPC (Linctus Scillae Opiatus pro Infantibus) 247 (Mistura Ferri et Ammonii Citratis pro Infantibus) 242 Compound Tolu Linctus Paediatric BPC Ferrous Sulphate Mixture BPC (Linctus Tolutanus Compositus pro Infantibus) 247 (Mistura Ferri Sulphatis) 242 . is no preservative and hence would attract a two-week This product would be Recently Prepared as Double Strength discard date. the astringent action of the rhubarb predominates. Rhubarb is therefore Belladonna Mixture Paediatric BPC (Mistura used as an astringent bitter in products such as this. would attract a four-week discard date. . Chloroform Water BP acts as a preservative and therefore Use: This product was used as an expectorant. page 744) Ingredients Quantities Ingredients Quantities Sodium Citrate BP 50 g Sodium Bicarbonate BP 30 mL Sodium Nitrite BP 3g Concentrated Compound Gentian Infusion BP 50 mL Strong Ammonium Acetate Solution BP 50 mL Compound Rhubarb Tincture BP 100 mL Concentrated Camphor Water BP 25 mL Concentrated Peppermint Emulsion BP 25 mL Water to 1000 mL Double Strength Chloroform Water BP 500 mL Water to 1000 mL Dose: 10–20 mL. Dose: 10–20 mL. The gentian acts as a bitter. page 746) Glycerol BP 100 mL Ingredients Quantities Benzoic Acid Solution BP 20 mL Compound Orange Spirit BP 2 mL Light Magnesium Carbonate BP 50 g Water to 1000 mL Sodium Bicarbonate BP 80 g Concentrated Peppermint Emulsion BP 25 mL Dose: Child up to 1 year – 5 mL. Use: This product was used to treat colic. Belladonna pro Infantibus) (BPC 1973. Use: This product was used as an antacid. Double Strength Chloroform Water BP 500 mL This product would be Recently Prepared as Benzoic Acid BP Water to 1000 mL acts as a preservative and therefore would attract a four-week discard date. page 737) Ingredients Quantities Belladonna Tincture BP 30 mL Magnesium Carbonate Mixture BPC (Mistura Syrup BP 200 mL Magnesii Carbonatis) (BPC 1973. page 1185) Gentianae cum Rheo) (BPC 1973. This product would need to be Freshly Prepared as there Dose: 10–20 mL. Use: This product was used to stimulate appetite. Internal mixtures | 233 Saline Mixture BPC (Mistura Diaphoretica) Gentian and Rhubarb Mixture BPC (Mistura (BPC 1968. 1–5 years – 10 mL. Although known for its purgative action in low doses. This product would be Recently Prepared as Double Strength Chloroform Water BP acts as a preservative and therefore would attract a four-week discard date. cystitis). page 746) Citratis) (BP 1988. 1–5 years – 10 mL. Use: This product was used to treat inflammatory conditions of the bladder (e. Water to 1000 mL This product would be Recently Prepared as Double Strength Chloroform Water BP acts as a preservative and therefore Dose: 10 mL well diluted with water. This product would be Recently Prepared as Double Use: This product was used as an antacid. Strength Chloroform Water BP acts as a preservative and therefore would attract a four-week discard date. ginger syrup or liquorice. page 724) Double Strength Chloroform Water BP 300 mL Ingredients Quantities Water to 1000 mL Chalk BP 20 g Dose: 10–20 mL. page 747) Ingredients Quantities Magnesium Sulphate BP 400 g Light Magnesium Carbonate BP 50 g Paediatric Chalk Mixture BP (Mistura Cretae Concentrated Peppermint Emulsion BP 25 mL pro Infantibus) (BP 1988.234 | Product formulae Aromatic Magnesium Carbonate Mixture BPC Potassium Citrate Mixture BP (Mistura Potassii (Mistura Carminativa) (BPC 1973.g. (Mistura Alba) (BPC 1973. . would attract a four-week discard date. Use: This product was used in the treatment of diarrhoea as Chalk BP acts as an adsorbent. page 748) Ingredients Quantities Ingredients Quantities Light Magnesium Carbonate BP 30 g Potassium Citrate BP 300 g Sodium Bicarbonate BP 50 g Citric Acid BP 50 g Aromatic Cardamom Tincture BP 30 mL Syrup BP 250 mL Double Strength Chloroform Water BP 500 mL Quillaia Tincture BP 10 mL Water to 1000 mL Lemon Spirit BP 5 mL Double Strength Chloroform Water BP 300 mL Dose: 10–20 mL. Tragacanth BP 2g This product would be Recently Prepared as Double Strength Syrup BP 100 mL Chloroform Water BP acts as a preservative and therefore Concentrated Cinnamon Water BP 4 mL would attract a four-week discard date. Dose: Child up to 1 year – 5 mL. Potassium Citrate BP makes the urine less acidic and causes Magnesium Sulphate Mixture BPC a mild diuresis. fruit syrups. Double Strength Chloroform Water BP 500 mL The taste of this preparation is unpalatable and it was Water to 1000 mL suggested that the taste may further be disguised by the addition of syrup. Strength Chloroform Water BP acts as a preservative and therefore would attract a four-week discard date. Use: This product was used as a laxative because of the This product would be Recently Prepared as Double purgative action of the Magnesium Sulphate BP. page 1158) Ingredients Quantities Calcium Carbonate BP 10 g Light Magnesium Carbonate BP 10 g Ferrous Sulphate Mixture Paediatric BP Sodium Bicarbonate BP 10 g (Mistura Ferri Sulphatis pro Infantibus) Aromatic Cardamom Tincture BP 10 mL (BP 1988. Freshly boiled and cooled purified water is used in this Cascara and Belladonna Mixture BPC (Mistura preparation to help prevent discoloration. Concentrated Anise Water BP 5 mL This product would be Recently Prepared and would attract Double Strength Chloroform Water BP 500 mL a four-week discard date. Orange Syrup BP 100 mL Use: For diarrhoea. 1–5 years – 10 mL. Well diluted with water: up to 1 year – 5 mL. Ferrous Sulphate BP 12 g This product would be Recently Prepared and would attract a Ascorbic Acid BP 2g four-week discard date. 1–5 years – 10 mL. Double Strength Chloroform Water BP 500 mL Freshly boiled and cooled purified water to 1000 mL Dose: Child. This product Cascarae et Belladonnae) (BPC 1973. . page 735) Ingredients Quantities Ingredients Quantities Ammonium Bicarbonate BP 20 g Belladonna Tincture BP 100 mL Liquid Liquorice Extract BP 50 mL Chloroform Spirit 50 mL Ipecacuanha Tincture BP 30 mL Aluminium Hydroxide Gel BP to 1000 mL Concentrated Camphor Water BP 10 mL Dose: 5 mL suitably diluted. Dose: 10–20 mL. page 738) would be Recently Prepared as Double Strength Chloroform Ingredients Quantities Water BP acts as a preservative and therefore would attract a four-week discard date. Use: This product was used to treat iron-deficiency anaemia. Water to 1000 mL Use: Used to treat indigestion and colic. Internal mixtures | 235 Ammonia and Ipecacuanha Mixture BP Aluminium Hydroxide and Belladonna Mixture (Mistura Expectorans) (BP 1988. page 734) Syrup BP 100 mL Chloroform Water BP to 1000 mL Ingredients Quantities Dose: Up to 1 year – 5 mL. consideration must be Cascara Elixir BP 200 mL given to the tendency of the ferrous ion to oxidise the Belladonna Tincture BP 50 mL ferric ion. and guidance to Double Strength Chloroform Water BP 500 mL discard the product should discoloration occur would be Water to 1000 mL advisable. which will cause discoloration. The Compound Calcium Carbonate Mixture Ammonium Bicarbonate BP is irritant to mucous Paediatric BPC (Mistura Calcii Carbonatis membranes and is used in small doses as a reflex Composita pro Infantibus) (BPC 1968. expectorant. This product would be Recently Prepared as Double Strength Chloroform Water BP acts as a preservative and therefore would attract a four-week discard date. However. Dose: 10–20 mL. page 719) BPC (BPC 1973. This product would be Recently Prepared and attract a four-week discard date Use: Constipation. Use: This product was used as an expectorant. . Dose: 10–20 mL. Ipecacuanha and Squill Linctus Paediatric BPC Use: To treat trigeminal neuralgia and migraine. page 743) Syrup BP to 1000 mL Ingredients Quantities Dose: 5 mL. Liquid Liquorice Extract BP 30 mL This product would be Recently Prepared and would attract Double Strength Chloroform Water BP 500 mL a four-week discard date. page 744) Gelsemium and Hyoscyamus Mixture Compound BPC (Mistura Gelsemii et Ingredients Quantities Hyoscyami Composita) (BPC 1973. Use: Because of the bitter taste of the nux vomica this was also a tonic. (Mistura Gentianae Alkalina cum Nuce Vomica) page 740) (BPC 1973. (Mist Tussi Rubra pro Inf) (BPC 1973. Double Strength Chloroform Water BP 500 mL Water to 1000 mL Dose: 10–20 mL. This product would be Recently Prepared and would attract a four-week discard date. This product would be Recently Prepared and would attract Nux Vomica Tincture BP 50 mL a four-week discard date. Alkaline Gentian Mixture with Phenobarbitone BPC (Mistura Gentianae Alkalina cum Phenobarbitono) (BPC 1973. Use: Pain in gout. Acid Gentian Mixture BP to 1000 mL Use: Expectorant. page 743) Phenobarbitone Sodium BP 1.5 g Alkaline Gentian Mixture BP to 1000 mL Ingredients Quantities Dose: 10–20 mL.236 | Product formulae Colchicum and Sodium Salicylate Mixture BPC Gentian Alkaline Mixture with Nux Vomica BPC (Mistura Colchici et Sodii Salicylate) (BPC 1973. page 744) Ingredients Quantities Ingredients Quantities Colchicum Tincture BP 100 mL Nux Vomica Tincture BP 50 mL Sodium Salicylate BP 100 g Alkaline Gentian Mixture BP to 1000 mL Potassium Bicarbonate BP 100 g Dose: 10–20 mL. Water to 1000 mL Use: Because of the bitter taste of the nux vomica this was Dose: 10–20 mL. This product would be Recently Prepared and attract a four-week discard date.5 mL (Mistura Gentianae Acida cum Nuce Vomica) Blackcurrant Syrup BP 500 mL (BPC 1973. Potassium Bromide BP 50 g Use: As a sedative. page 723) Ingredients Quantities Ipecacuanha Tincture BP 20 mL Squill Tincture BP 30 mL Gentian Acid Mixture with Nux Vomica BPC Compound Orange Spirit 1. also a tonic. This product would be Recently Prepared and would attract a four-week discard date. Gelsemium Tincture BP 30 mL This product must be Freshly Prepared and will therefore Hyoscyamus Tincture 100 mL attract a two-week discard date. Internal mixtures | 237 Ipecacuanha Mixture Paediatric BPC (Mistura Lobelia and Stramonium Mixture Compound Ipecacuanha pro Infantibus) (BPC 1973, BPC (Mistura Lobeliae et Stramonii Composta) page 744) (BPC 1973, page 746) Ingredients Quantities Ingredients Quantities Ipecacuanha Tincture BP 20 mL Lobelia Etheral Tincture BP 50 mL Sodium Bicarbonate BP 20 g Stramonium Tincture BP 100 mL Tolu Syrup BP 200 mL Potassium Iodide BP 20 g Double Strength Chloroform Water BP 500 mL Tragacanth Mucilage 100 mL Water to 1000 mL Double Strength Chloroform Water BP 500 mL Water to 1000 mL Dose: up to 1 year – 5 mL; 1–5 years – 10 mL. This product would be Recently Prepared and would attract a Dose: 10 mL. four-week discard date. This product would be Recently Prepared and would attract a Use: Cough mixture. four-week discard date. Use: To treat asthma. Paediatric Opiate Ipecacuanha Mixture BPC (BPC 1973, page 744) Nux Vomica Mixture Acid BPC (Mistura Nucis Vomicae Acida) (BPC 1973, Ingredients Quantities page 748) Ipecacuanha Tincture BP 20 mL Camphorated Opium Tincture 30 mL Ingredients Quantities Sodium Bicarbonate BP 20 g Nux Vomica Tincture BP 50 mL Tolu Syrup BP 200 mL Dilute Hydrochloric Acid BP 50 mL Double Strength Chloroform Water BP 500 mL Double Strength Chloroform Water BP 500 mL Water to 1000 mL Water to 1000 mL Dose: up to 1 year – 5 mL; 1–5 years – 10 mL. Dose: 10–20 mL. This product would be Recently Prepared and would attract a This product would be Recently Prepared and would attract a four-week discard date. four-week discard date. Use: Cough mixture. Use: Bitter to stimulate appetite. Ipecacuanha and Ammonia Mixture Paediatric Nux Vomica Mixture Alkaline BPC BPC (Mistura Ipecacuanhae et Ammoniae pro (Mistura Nucis Vomicae Alkalina) (BPC 1973, Infantibus) (BPC 1973, page 745) page 749) Ingredients Quantities Ingredients Quantities Ipecacuanha Tincture BP 20 mL Nux Vomica Tincture BP 50 mL Ammonium Bicarbonate BP 6g Sodium Bicarbonate BP 50 g Sodium Bicarbonate BP 20 g Double Strength Chloroform Water BP 500 mL Tolu Syrup BP 100 mL Water to 1000 mL Double Strength Chloroform Water BP 500 mL Dose: 10–20 mL. Water to 1000 mL This product would be Recently Prepared and would attract a Dose: up to 1 year – 5 mL; 1–5 years – 10 mL. four-week discard date. This product would be Recently Prepared and would attract a Use: Bitter to stimulate appetite. four-week discard date. Use: Expectorant cough mixture. 238 | Product formulae Compound Camphorated Opium Mixture BPC Compound Rhubarb Mixture BPC (Mistura Rhei (Mistura Opii Camphorata Composita) Composita) (BPC 1973, page 752) (BPC 1973, page 749) Ingredients Quantities Ingredients Quantities Compound Rhubarb Tincture BP 100 mL Camphorated Opium Tincture BP 100 mL Light Magnesium Carbonate BP 50 g Ammonium Bicarbonate BP 10 g Sodium Bicarbonate BP 50 g Strong Ammonium Acetate Solution 100 mL Strong Ginger Tincture BP 30 mL Water to 1000 mL Double Strength Chloroform Water BP 500 mL Water to 1000 mL Dose: 10–20 mL This product would be Recently Prepared and would attract a Dose: 10–20 mL. four-week discard date. This product would be Recently Prepared and would attract a Use: Expectorant cough mixture. four-week discard date. Use: To treat constipation. Potassium Citrate and Hyoscyamus Mixture BPC (Mistura Potassii Citratis et Hyoscyamus) Compound Rhubarb Mixture Paediatric BPC (BPC 1973, page 751) (Mistura Rhei Composita pro Infantibus) (BPC 1973, page 752) Ingredients Quantities Ingredients Quantities Potassium Citrate BP 300 g Hyoscyamus Tincture BP 200 mL Compound Rhubarb Tincture BP 60 mL Citric Acid BP 50 g Light Magnesium Carbonate BP 15 g Lemon Spirit BP 5 mL Sodium Bicarbonate BP 15 g Quillaia Tincture BP 10 mL Ginger Syrup BP 100 mL Syrup BP 250 mL Double Strength Chloroform Water BP 500 mL Double Strength Chloroform Water BP 200 mL Water to 1000 mL Water to 1000 mL Dose: Up to 1 year – 5 mL; 1–5 years – 10 mL. Dose: 10 mL well diluted with water. This product would be Recently Prepared and would attract a This product would be Recently Prepared and would attract a four-week discard date. four-week discard date. Use: To treat constipation. Use: Treatment of cystitis. Ammoniated Rhubarb and Soda Mixture BPC Ammoniated Potassium Iodide Mixture BPC (Mistura Rhei Ammoniate et Sodae) (BPC 1973, (Mistura Potassii Iodide Ammoniata) (BPC 1973, page 752) page 751) Ingredients Quantities Ingredients Quantities Rhubarb Powder BP 25 g Potassium Iodide BP 15 g Sodium Bicarbonate BP 80 g Ammonium Bicarbonate BP 15 g Ammonium Bicarbonate BP 20 g Liquorice Liquid Extract 100 mL Conc Peppermint Emulsion BP 25 mL Double Strength Chloroform Water BP 500 mL Double Strength Chloroform Water BP 500 mL Water to 1000 mL Water to 1000 mL Dose: 10–20 mL. Dose: 10–20 mL. This product would be Recently Prepared and would attract a This product would be Recently Prepared and would attract a four-week discard date. four-week discard date. Use: Expectorant. Use: Laxative. Internal mixtures | 239 Compound Sodium Chloride Mixture BPC Stramonium and Potassium Iodide Mixture (Mistura Sodii Chloridi Composita) (BPC 1973, BPC (Mistura Stramonii et Potassii Iodidi) page 753) (BPC 1973, page 753) Ingredients Quantities Ingredients Quantities Sodium Chloride BP 20 g Stramonium Tincture BP 125 mL Sodium Bicarbonate BP 50 g Potassium Iodide BP 20 g Double Strength Chloroform Water BP 500 mL Double Strength Chloroform Water BP 500 mL Water to 1000 mL Water to 1000 mL Dose: 10–20 mL in a tumblerful of hot water, sipped slowly Dose: 10 mL. twice daily. This product would be Recently Prepared and would attract a This product would be Recently Prepared and would attract four-week discard date. a four-week discard date. Use: Asthma. Use: Emetic. Gentian Alkaline Mixture BP (Mistura Sodium Citrate Mixture BPC (Mistura Sodium Gentianae cum Soda) (BP 1988, page 736) Citratis) (BPC 1973, page 753) Ingredients Quantities Ingredients Quantities Concentrated Compound Gentian Infusion BP 100 mL Sodium Citrate BP 300 g Sodium Bicarbonate BP 50 g Citric Acid BP 50 g Double Strength Chloroform Water BP 500 mL Lemon Spirit BP 5 mL Water to 1000 mL Quillaia Tincture BP 10 mL Dose: 10–20 mL. Syrup BP 250 mL This product would be Recently Prepared as Double Double Strength Chloroform Water BP 300 mL Strength Chloroform Water BP acts as a preservative and Water to 1000 mL therefore would attract a four-week discard date. Dose: 10 mL well diluted with water. Use: This product was used to stimulate appetite. This product would be Recently Prepared and would attract a The gentian acts as a bitter. four-week discard date. Use: Treatment of cystitis. Gentian Acid Mixture BPC (Mistura Gentianae Acida) (BPC 1973, page 743) Sodium Salicylate Mixture BPC (Mistura Sodii Salicylatis) (BPC 1973, page 753) Ingredients Quantities Concentrated Compound Gentian Infusion BP 100 mL Ingredients Quantities Dilute Hydrochloric Acid BP 50 mL Sodium Salicylate BP 50 g Double Strength Chloroform Water BP 500 mL Sodium Metabisulphite BP 1g Water to 1000 mL Concentrated Orange peel infusion BP 50 mL Dose: 10–20 mL. Double Strength Chloroform Water BP 500 mL This product would be Recently Prepared as Double Water to 1000 mL Strength Chloroform Water BP acts as a preservative and Dose: 10–20 mL. therefore would attract a four-week discard date. This product would be Recently Prepared and would attract a Use: This product was used to stimulate appetite. four-week discard date. The gentian acts as a bitter. Use: Analgesic. 240 | Product formulae Magnesium Trisilicate Mixture BP (Mistura Kaolin Mixture BP (Mistura Kaolini) (BP 1988, Magnesii Trisilicatis) (BP 1988, page 740) page 738) Ingredients Quantities Ingredients Quantities Magnesium Trisilicate BP 50 g Light Kaolin BP 200 g Light Magnesium Carbonate BP 50 g Light Magnesium Carbonate BP 50 g Sodium Bicarbonate BP 50 g Sodium Bicarbonate BP 50 g Concentrated Peppermint Emulsion BP 25 mL Concentrated Peppermint Emulsion BP 25 mL Double Strength Chloroform Water BP 500 mL Double Strength Chloroform Water BP 500 mL Water to 1000 mL Water to 1000 mL Dose: 10–20 mL. Dose: 10 mL. This product would be Recently Prepared as Double This product would be Recently Prepared as Double Strength Chloroform Water BP acts as a preservative and Strength Chloroform Water BP acts as a preservative and therefore would attract a four-week discard date. therefore would attract a four-week discard date. Use: This product was used to treat Use: This product was used to treat colitis, enteritis, indigestion/dyspepsia. dysentery and diarrhoea associated with food poisoning. Sodium Salicylate Mixture Strong BP (Mistura Sodii Salicylatis Fortis) (BP 1988, page 751) Kaolin Mixture Paediatric BP (Mistura Kaolini pro Infantibus) (BP 1980, page 691) Ingredients Quantities Ingredients Quantities Sodium Salicylate BP 100 g Sodium Metabisulphite BP 1g Light Kaolin BP 200 g Concentrated Peppermint Emulsion BP 25 mL Raspberry Syrup BP 200 mL Double Strength Chloroform Water BP 500 mL Benzoic Acid Solution BP 20 mL Water to 1000 mL Amaranth Solution BP 10 mL Double Strength Chloroform Water BP 500 mL Dose: 10–20 mL. Water to 1000 mL This product would be Recently Prepared as Double Strength Chloroform Water BP acts as a preservative and Dose: Child up to 1 year – 5 mL; 1–5 years – 10 mL. therefore would attract a four-week discard date. This product would be Recently Prepared as Double Use: This product was used to treat pain and Strength Chloroform Water BP acts as a preservative and inflammation, as sodium salicylate has analgesic, therefore would attract a four-week discard date. anti-inflammatory and antipyretic actions. Use: This was used for the treatment of diarrhoea in children. Ammonium Chloride Mixture BP (Mistura Ammonii Chloridi) (BP 1988, page 720) Ingredients Quantities Ammonium Chloride BP 100 g Liquorice Liquid Extract BP 100 mL Aromatic Ammonia Solution BP 50 mL Water to 1000 mL Dose: 10–20 mL. This product would be Recently Prepared and therefore would attract a four-week discard date. Use: This product was used as an expectorant cough mixture. Internal mixtures | 241 Belladonna and Ephedrine Mixture Paediatric Ammonium Chloride and Morphine Mixture BPC (Mistura Belladonnae et Ephedrinae pro BP (Mistura Tussi Sedativa) (BP 1988, page 720) Infantibus) (BPC 1973, page 737) Ingredients Quantities Ingredients Quantities Ammonium Chloride BP 30 g Belladonna Tincture BP 30 mL Ammonium Bicarbonate BP 20 g Potassium Iodide BP 10 g Liquorice Liquid Extract BP 50 mL Ephedrine Hydrochloride BP 1.5 g Chloroform and Morphine Tincture BP 30 mL Syrup BP 100 mL Water to 1000 mL Liquorice Liquid Extract BP 30 mL Dose: 10–20 mL. Concentrated Anise Water BP 20 mL This product would be Recently Prepared and therefore Benzoic Acid Solution BP 20 mL would attract a four-week discard date. Water to 1000 mL Use: This product was used as an expectorant. Dose: Child up to 1 year – 5 mL; 1–5 years – 10 mL. This product would be Recently Prepared as benzoic acid acts as a preservative and therefore would attract a four-week discard date. Chalk with Opium Mixture Aromatic BPC (Mistura Use: This product would have been used to treat asthma or whooping cough. Cretae Aromatica cum Opio) (BPC 1973, page 739) Ingredients Quantities Aromatic Chalk Powder BP 130 g Tragacanth Powder BP 2g Belladonna and Ipecacuanha Mixture Aromatic Ammonia Solution BP 50 mL Paediatric BPC (BPC 1973, page 738) Compound Cardamom Tincture BP 50 mL Catechu Tincture BP 50 mL Ingredients Quantities Opium Tincture BP 50 mL Belladonna Tincture BP 30 mL Double Strength Chloroform Water BP 500 mL Ipecacuahna Tincture BP 20 mL Water to 1000 mL Sodium Bicarbonate BP 20 g Dose: Adult 10–20 mL. Child up to 1 year – 5 mL; 1–5 Tolu Syrup BP 200 mL years – 10 mL. Double Strength Chloroform Water BP 500 mL This product would be Recently Prepared as Double Water to 1000 mL Strength Chloroform Water BP acts as a preservative and Dose: Child up to 1 year – 5 mL; 1–5 years – 10 mL. therefore would attract a four-week discard date. This product would need to be Freshly Prepared and Use: This product was used to treat diarrhoea. therefore would attract a two-week discard date. Two weeks would be suitable because although the product contains Double Strength Chloroform Water BP as a preservative the high vegetable content in the form of tinctures makes it more Chloral Mixture BP (Mist Chloral) (BP 1988, liable to microbial contamination. Use: This product would have been used to treat asthma page 725) or whooping cough. Ingredients Quantities Chloral Hydrate BP 100 g Syrup BP 200 mL Water to 1000 mL Dose: Adult 5–20 mL at bedtime. Child 1–5 years – 2.5–5 mL at bedtime; 6–12 years – 5–10 mL at bedtime. Each dose should be taken well diluted with water because of the possible irritant action of the chloral hydrate. This product would be Recently Prepared and therefore would attract a four-week discard date. Use: This product was used as a hypnotic and sedative. 242 | Product formulae Ferric Ammonium Citrate Mixture BPC (Mist Ferrous Sulphate Mixture BPC (Mistura Ferri Ferr et Ammon Cit) (BPC 1973, page 741) Sulphatis) (BPC 1973, page 742) Ingredients Quantities Ingredients Quantities Ferric Ammonium Citrate BP 200 g Ferrous Sulphate BP 30 g Double Strength Chloroform Water BP 500 mL Ascorbic Acid BP 1g Water to 1000 mL Orange Syrup BP 50 mL Double Strength Chloroform Water BP 500 mL Dose: 10 mL. Freshly boiled and cooled purified water to 1000 mL This product would be Recently Prepared as Double Strength Chloroform Water BP acts as a preservative and Dose: 10 mL well diluted with water. therefore would attract a four-week discard date. Freshly boiled and cooled purified water is used in this Use: This product was used to treat iron-deficiency preparation to help prevent discoloration. This product anaemia. would be Recently Prepared as Double Strength Chloroform Water BP acts as a preservative and therefore would attract a four-week discard date. However, consideration must be given to the tendency of the ferrous ion to oxidise to the ferric ion, which will cause the discoloration, and guidance Ferric Ammonium Citrate Mixture Paediatric to discard the product should discoloration occur would be BPC (Mistura Ferri et Ammonii Citratis pro advisable. Infantibus) (BPC 1973, page 742) Use: This product was used to treat iron-deficiency anaemia. Ingredients Quantities Ferric Ammonium Citrate BP 80 g Compound Orange Spirit BP 2 mL Syrup BP 100 mL Double Strength Chloroform Water BP 500 mL Ipecacuanha and Morphine Mixture BPC Water to 1000 mL (Mistura Tussi Nigra) (BPC 1973, page 745) Dose: Child up to 1 year – 5 mL; 1–5 years – 10 mL. The Ingredients Quantities dose should be taken well diluted with water. Liquorice Liquid Extract BP 100 mL This product would be Recently Prepared as Double Chloroform and Morphine Tincture BP 40 mL Strength Chloroform Water BP acts as a preservative and Ipecacuanha Tincture BP 20 mL therefore would attract a four-week discard date. Water to 1000 mL Use: This product was used to treat iron-deficiency anaemia in children. Dose: 10 mL. This product would be Recently Prepared and therefore would attract a four-week discard date. Use: This product was used as an expectorant. Codeine Linctus BPC (Linctus Codeinae) (BPC 1973. It was the official 'Gripe Mixture'. The atropine and hyoscine were adsorbed on to the magnesium trisilicate and only released at pH less than 2 – a level that was unlikely to be achieved in this preparation. Use: This product was used to treat flatulence and vomiting in children. Use: Cough suppressant. therefore would attract a four-week discard date. page 738) (Mist Sod Bicarb pro Inf) (BPC 1973. Water to 1000 ML This product would be Recently Prepared and therefore would attract a four-week discard date. 1–5 years – 10 mL. Magnesium Trisilicate and Belladonna Mixture BPC (Mist Mag Trisil et Bellad) (BPC 1973. page 668) Light Magnesium Carbonate BP 50 g Ingredients Quantities Sodium Bicarbonate BP 50 g Belladonna Tincture BP 50 mL Chloral Hydrate BP 40 g Concentrated Peppermint Emulsion BP 25 mL Water 20 mL Double Strength Chloroform Water BP 500 mL Blackcurrant Syrup BP 200 mL Syrup BP to 1000 mL Dose: 10–20 mL. Dose: Child up to 1 year – 5 mL. This product would be Recently Prepared as Double Strength Chloroform Water BP acts as a preservative and therefore would attract a four-week discard date. page 747) Ingredients Quantities Chloral Elixir Paediatric BPC (Elixir Chloralis pro Magnesium Trisilicate BP 50 g Infantibus) (BPC 1973. Use: This product is used to treat diarrhoea. Use: This product was used as an antacid. page 722) Ingredients Quantities Codeine Phosphate BP 3g Compound Tartrazine Solution BP 10 mL Benzoic Acid Solution BP 20 mL Chloroform Spirit BP 20 mL Water 20 mL Lemon Syrup BP 200 mL Syrup BP to 1000 mL Dose: 5 mL. . This product would be Recently Prepared as Double Dose: Child up to 1 year – 5 mL. Internal mixtures | 243 Kaolin and Morphine Mixture BP (Mistura Sodium Bicarbonate Paediatric Mixture BPC Kaolini Sedativa) (BP 1988. page 752) Ingredients Quantities Ingredients Quantities Light Kaolin BP 200 g Sodium Bicarbonate BP 10 g Sodium Bicarbonate BP 50 g Syrup BP 370 mL Chloroform and Morphine Tincture BP 40 mL Concentrated Dill Water BP 20 mL Water to 1000 mL Weak Ginger Tincture BP 10 mL Double Strength Chloroform Water BP 500 mL Dose: 10 mL. Strength Chloroform Water BP acts as a preservative and Use: Short-term treatment of insomnia. whisky. The quantities of diamorphine and cocaine can be altered in accordance with doctor's instruction. Use: Pain in terminal illness.g.). brandy. Cocaine Hydrochloride BP 1g Alcohol (90%) BP 125 mL Syrup BP 250 mL Chloroform Water to 1000 mL Ephedrine Elixir BPC (Elixir Ephedrinae) Dose: As determined by physician in accordance with the (BPC 1973. Morphine and Cocaine Elixir BPC (BPC 1973.g. gin. brandy. gin. whisky. The quantities of diamorphine and cocaine can be altered in accordance with Ingredients Quantities doctor's instruction. Chloroform Water BP to 1000 mL Use: Cough suppressant. etc. Syrup BP 250 mL Discard date: Two weeks as it should be Freshly Prepared. gin.). Discard date: Two weeks as it should be Freshly Prepared. page 669) Use: Pain in terminal illness. The quantities of morphine and cocaine can be altered in accordance with doctor's instruction. 1–5 years – 5 mL. 6–12 years – 10 mL. . page 671) needs of the patient. Discard date: Two weeks as it should be Freshly Prepared. Note: The alcohol used quite often was the alcohol Ingredients Quantities of preference to the patient (e. Diamorphine and Cocaine Elixir BPC (BPC 1973. whisky. page 669) Dose: Adult 5–10 mL. Note: The alcohol used quite often was the alcohol of preference to the patient (e.). Ingredients Quantities Use: Bronchodilator. etc.5 mL. Dose: As determined by physician in accordance with the needs of the patient. Child up to 1 year – 2.g. page 722) page 669) Ingredients Quantities Ingredients Quantities Codeine Linctus BP 200 mL Morphine Hydrochloride BP 1g Syrup BP to 1000 mL Cocaine Hydrochloride BP 1g Alcohol (90%) BP 125 mL Dose: Child up to 1 year – 5 mL.244 | Product formulae Codeine Linctus Paediatric BPC (BPC 1973. Diamorphine Hydrochloride BP 1g Cocaine Hydrochloride BP 1g Alcohol (90%) BP 125 mL Chlorpromazine Elixir BP 250 mL Chloroform Water BP to 1000 mL Dose: As determined by physician in accordance with the needs of the patient. etc. Lemon Spirit BP 0. Diamorphine Hydrochloride BP 1g brandy.2 mL Use: Pain in terminal illness. Compound Tartrazine Solution BP 10 mL Note: The alcohol used quite often was the alcohol of Chloroform Spirit BP 40 mL preference to the patient (e. Water 60 mL Alcohol (90%) BP 100 mL Invert Syrup BP 200 mL Glycerol BP 200 mL Diamorphine. Ephedrine Hydrochloride BP 3g Discard date: Two weeks as it should be Freshly Prepared. Cocaine and Chlorpromazine Syrup BP to 1000 mL Elixir BPC (BPC 1973. 1–5 years – 10 mL. If dilution is necessary. Anticonvulsant. Internal mixtures | 245 Paracetamol Elixir Paediatric BPC (Elixir Phenobarbitone Elixir BPC (Elixir Paracetamolis pro Infantibus) (BPC 1973. Child up to 5 years – 5 mL tds Invert Syrup BP 275 mL increased to 10 mL tds. chloroform water is the diluent of choice. night-time dose. Diamorphine Linctus BPC (Linctus Isoniazid Elixir BPC (BPC 1973. Double Strength Chloroform Water BP 400 mL This product would be Recently Prepared and therefore Water to 1000 mL would attract a four-week discard date. page 672) Diamorphinae) (BPC 1973. Syrup should not be used as isoniazid is unstable in the presence of sugars.5–10 mL. Use: Analgesia. Dose: Child twice daily. Use: Treatment of pulmonary tuberculosis.5–5 mL. page 723) Ingredients Quantities Ingredients Quantities Isoniazid BP 10 g Diamorphine Hydrochloride BP 0. Glycerol BP to 1000 mL Use: Sedative to control epileptic seizures and as Dose: Child up to 1 year – 5 mL. Up to 1 year – 2. page 675) page 674) Ingredients Quantities Ingredients Quantities Phenobarbitone BP 3g Paracetamol BP 24 g Compound Tartrazine Solution BP 10 mL Amaranth Solution BP 2 mL Compound Orange Spirit BP 24 mL Chloroform Spirit BP 20 mL Alcohol (90%) BP 400 mL Concentrated Raspberry Juice BP 25 mL Glycerol BP 400 mL Alcohol (95%) BP 100 mL Water to 1000 mL Propylene Glycol BP 100 mL Dose: Adult 5–10 mL. 1–5 Use: To treat terminal cough. long-acting barbiturate used to aid sleep as a The elixir should not be diluted.5 g Compound Tartrazine solution BP 12 mL Sodium Citrate BP 12 g Glycerol BP 250 mL Concentrated Anise Water BP 10 mL Oxymel BP 250 mL Compound Tartrazine Solution BP 10 mL Syrup BP to 1000 mL Glycerol BP 200 mL Dose: 2. years – 5–10 mL.6 g Citric Acid BP 2. . 1–5 years – 10 mL. This product would be Recently Prepared and therefore would attract a four-week discard date. Phenobarbitoni) (BPC 1973. Use: Cough suppressant. This product would be Recently Prepared and therefore This product would be Recently Prepared and therefore would attract a four-week discard date.4 g Citric Acid BP 25 g Compound Tartrazine Solution BP 8 mL Concentrated Anise Water BP 10 mL Water 120 mL Amaranth Solution BP 15 mL Glycerol BP 250 mL Chloroform Spirit BP 60 mL Tolu Syrup BP to 1000 mL Syrup BP to 1000 mL Dose: 5 mL. Use: Demulcent cough mixture. page 725) Pholcodine Linctus BPC (Linctus Pholcodinae) (BPC 1973. Pholcodine Linctus Strong BPC (Linctus Simple Linctus Paediatric BPC (Linctus Pholcodinae Fortis) (BPC 1973. This product would be Recently Prepared and therefore would attract a four-week discard date. Dose: 5 mL. This product would be Recently Prepared and therefore would This product would be Recently Prepared and therefore attract a four-week discard date. Use: Cough suppressant. Linctus Squill Opiate BPC (also known as Gees Linctus) (Linctus Scillae Opiatus) (BPC 1973. Use: Demulcent cough mixture. page 724) Ingredients Quantities Ingredients Quantities Methadone Hydrochloride BP 0. Use: Cough suppressant. page 724) Simplex pro Infantibus) (BPC 1973. Dose: 5 mL. would attract a four-week discard date.246 | Product formulae Methadone Linctus BPC (Linctus Methadoni) Simple Linctus BPC (Linctus Simplex) (BPC 1973. Dose: 5 mL. would attract a four-week discard date. Use: To treat terminal cough. page 723) (BPC 1973. Chloroform Spirit BP 150 mL This product would be Recently Prepared and therefore Syrup BP to 1000 mL would attract a four-week discard date. page 725) Ingredients Quantities Pholcodine BP 2g Ingredients Quantities Citric acid BP 20 g Simple Linctus BP 250 mL Amaranth Solution BP 2 mL Syrup BP to 1000 mL Compound Tartrazine Solution BP 20 mL Dose: Child 5–10 mL. . page 724) Ingredients Quantities Ingredients Quantities Squill Oxymel BP 300 mL Camphorated Opium Tincture BP 300 mL Strong Pholcodine Linctus BP 500 mL Tolu Syrup BP 300 mL Syrup BP 500 mL Dose: 5 mL. Use: Demulcent cough mixture. This product would be Recently Prepared and therefore Use: Cough suppressant. page 725) Ingredients Quantities Ingredients Quantities Squill Oxymel BP 60 mL Citric Acid BP 6g Camphorated Opium Tincture BP 60 mL Benzaldehyde Spirit BP 2 mL Tolu Syrup BP 60 mL Compound Tartrazine Solution BP 10 mL Glycerol BP 200 mL Glycerol BP 200 mL Syrup BP to 1000 mL Invert Syrup BP 200 mL Tolu Syrup BP to 1000 mL Dose: Child 5–10 mL. . (Linctus Tolutanus Compositus pro Infantibus) page 725) (BPC 1973. This product would be Recently Prepared and therefore Dose: Child 5–10 mL. would attract a four-week discard date. Internal mixtures | 247 Squill Linctus Opiate Paediatric BPC (Linctus Compound Tolu Linctus Paediatric BPC Scillae Opiatus pro Infantibus) (BPC 1973. would attract a four-week discard date. . Applic) (BP 1988. Use: Soap Liniment is a mild counterirritant that is used in the treatment of sprains and bruises. Zinc Sulphate Lotion BP (Lotio Rubra) 250 also known as Opodeldoc) 249 Calamine Lotion Oily BP (Lotio Calamine Oleosa) 250 Calamine Lotion BP (Calam Lot) 250 White Liniment BPC (Linimentum Album) 251 Salicylic Acid Lotion BP (Lotio Acidi Salicylici) 250 Compound Calamine Application BPC Sulphur Lotion Compound BPC (Lotio Sulph Co) 250 (Applicatio Calaminae Composita) 251 Benzyl Benzoate Application BP (Benzyl Benz Soap Liniment BPC (Linimentum Saponis. lotions and applications Benzyl Benzoate Application BP Copper and Zinc Sulphates Lotion BPC (Benzyl Benz Applic) 249 (Dalibour Water) 250 Soap Liniment BPC (Linimentum Saponis. . page 726) Ingredients Quantities Benzyl Benzoate BP 250 g Ingredients Quantities Emulsifying Wax BP 20 g Camphor BP 40 g Freshly boiled and cooled purified water to 1000 mL Oleic Acid BP 40 g Directions: Apply over the whole body. Freshly boiled and cooled purified water to 1000 mL Not recommended for use in children. scabies and pediculosis. left for not Use: Used as an ascaricide in the treatment of less than seven days and filtered prior to dispensing. repeat without Alcohol 90% BP 700 mL bathing on the following day and wash off Potassium Hydroxide Solution BP 140 mL 24 hours later. page 621) also known as Opodeldoc) (BPC 1973.17 Liniments. This product should be prepared in advance. A third application may be Rosemary Oil BP 15 mL required in some cases. Salicylic Acid Lotion BP (Lotio Acidi Salicylici) Zinc Sulphate Lotion BP (Lotio Rubra) (BP 1988. page 682) Ingredients Quantities Ingredients Quantities Precipitated Sulphur BP 40 g Calamine BP 50 g Alcohol (95%) BP 60 mL Wool Fat BP 10 g Glycerin BP 20 mL Arachis Oil BP 500 mL Quillaia Tincture BP 5 mL Oleic Acid BP 5 mL Calcium Hydroxide Solution BP to 1000 mL Calcium Hydroxide Solution BP to 1000 mL Use: This product was used to treat acne. page 703) Ingredients Quantities Ingredients Quantities Salicylic Acid BP 20 g Zinc Sulphate BP 10 g Castor Oil BP 10 mL Amaranth Solution BP 10 mL Alcohol (95%) BP to 1000 mL Water to 1000 mL Use: Salicylic acid is a bacteriostatic and fungicide. page 729) Oleosa) (BP 1980. psoriasis. Use: Calamine Lotion Oily was used as a mild astringent to soothe irritating rashes such as prickly heat or chickenpox. page 702) (BP 1988. Reduces itching. etc. Freshly boiled and cooled purified water to 1000 mL Use: Used as a protective application to the skin. Sulphur Lotion Compound BPC Calamine Lotion Oily BP (Lotio Calamine (Lotio Sulph Co) (BPC 1973. Copper and Zinc Sulphates Lotion BPC page 702) (Dalibour Water) (BPC 1973. . indolent ulcers and to assist granulation. The Use: Lotio Rubra was used as an astringent lotion for lotion is used to treat chronic ulcers. page 727) Ingredients Quantities Ingredients Quantities Calamine BP 150 g Zinc Sulphate BP 15 g Zinc Oxide BP 50 g Copper Sulphate BP 10 g Bentonite BP 30 g Concentrated Camphor Water BP 25 mL Sodium Citrate BP 5g Water to 1000 mL Liquefied Phenol BP 5 mL Use: Dalibour Water was used as a wet dressing to treat Glycerin BP 50 mL eczema. dandruff. impetigo and intertrigo. eczema.250 | Product formulae Calamine Lotion BP (Calam Lot) (BP 1988. lotions and applications | 251 White Liniment BPC (Linimentum Album) Compound Calamine Application BPC (BPC 1973.5 g Ingredients Quantities Turpentine Oil BP 250 mL Calamine BP 100 g Oleic Acid BP 85 mL Zinc Oxide BP 50 g Dilute Ammonia Solution BP 45 mL Wool Fat BP 25 g Water 625 mL Zinc Stearate BP 25 g Use: Lin Alb was also known as White Embrocation. Also known as Compound Calamine Cream and Compound Calamine Liniment. The Yellow Soft Paraffin BP 250 g turpentine acts as a rubefacient and liniments such Liquid Paraffin BP 550 g as this were used for rheumatic pains and stiffness. page 648) Ingredients Quantities Ammonium Chloride BP 12. Use: Soothing application used to treat the discomfort of dermatitis and eczema. page 726) (Applicatio Calaminae Composita) (BPC 1973. . Liniments. . to treat fungal infections of the skin. Dose: Apply twice a day. Use: Calamine is a soothing astringent and this Use: Benzoic Acid BP has antifungal and antibacterial preparation is used to soothe rashes and properties and this ointment was commonly used itching. page 705) (Unguentum Calaminae) (BP 1988. page 706) Ingredients Quantities Ingredients Quantities Emulsifying Ointment BP 910 g Calamine BP 150 g Benzoic Acid BP 60 g White Soft Paraffin BP 850 g Salicylic Acid BP 30 g Dose: Apply when required. . also known as Compound Calamine Ointment BP 254 Salicylic Acid and Sulphur Ointment BPC (Ung Acid Salicyl et Sulph) 255 Zinc and Salicylic Acid Paste BP (Lassar's Paste) 254 Coal Tar Paste BPC (Pasta Picis Carbonis) 255 Zinc and Coal Tar Paste BP (White's Tar Paste) 254 Emulsifying Ointment BP (Ung Emulsif) 255 Simple Ointment BP (Ung Simp) 254 Ichthammol Ointment BP Sulphur Ointment BP 254 (Unguentum Ichthammolis) 255 Methyl Salicylate Ointment BP (Unguentum Methylis Salicylatis) 255 Compound Benzoic Acid Ointment BP Calamine Ointment BP (Whitfield's Ointment) (BP 1988.18 Ointments and pastes Compound Benzoic Acid Ointment BP Zinc Ointment BP (Ung Zinc) 255 (Whitfield's Ointment) 253 Cetrimide Emulsifying Ointment BP Calamine Ointment BP (Unguentum Calaminae) 253 (Unguentum Cetrimidi Emulsificans) 255 Cetomacrogol Emulsifying Ointment BP. Compound Zinc Paste BP (Co Zinc Paste) 255 also called Non-ionic Emulsifying Ointment BP 254 Salicylic Acid Ointment BP (Ung Acid Salicyl) 255 Calamine and Coal Tar Ointment BP. Other advantages include easy miscibility with any Zinc and Coal Tar Paste BP exudates. addition of active ingredient. page 868) removal from the scalp. high cosmetic acceptability and. properties. also called Cationic Emulsifying Ointment BP) Yellow Soft Paraffin BP 450 g can be made by replacing Cetomacrogol Emulsifying Starch BP 380 g Wax BP with Cetrimide Emulsifying Wax BP. Particularly suitable when easy removal from the skin is required. Picis Carbonis) (BP 1988. be incorporated. page 706) Zinc Oxide BP 240 g Ingredients Quantities Salicylic Acid BP 20 g White Soft Paraffin BP 500 g Starch BP 240 g Cetomacrogol Emulsifying Wax BP 300 g White Soft Paraffin BP 500 g Liquid Paraffin BP 200 g Dose: Apply twice a day. White/Yellow Soft Paraffin BP 850 g also known as Compound Calamine Dose: Apply when required. Ingredients Quantities Unguentum Cetrimidi Emulsificans (Cetrimide Emulsifying Ointment BP. page 713) Ingredients Quantities Wool Fat BP 50 g Hard Paraffin BP 50 g Cetostearyl Alcohol BP 50 g Calamine and Coal Tar Ointment BP. page 701) Zinc Oxide BP 125 g Ingredients Quantities Strong Coal Tar Solution BP 25 g Sulphur (precipitated) BP 100 g Dose: Apply once or twice daily. because of the emulsifying properties. Ointment BP (Unguentum Calaminae et Use: Used as an emollient or base for other ingredients. determined by the properties of the active ingredient to Use: Used to treat psoriasis and chronic atopic eczema. antipruritic and antiscaling Dose: Apply twice daily. Frequency determined by any Use: Used for hyperkeratoses. The choice of base ointment is Dose: Apply once or twice daily. page 706) Ingredients Quantities White Soft Paraffin BP 475 g Hydrous Wool Fat BP 250 g Calamine BP 125 g Sulphur Ointment BP (BP 1980. . Use: Used to treat acne and scabies. Dose: Apply when required. Similarly. page 868) BP (Unguentum Cetomacrogolis Emulsificans) Ingredients Quantities (BP 1988. Unguentum Emulsificans (Emulsifying Emulsifying Wax BP 50 g Ointment BP) is formed. Simple Ointment BP (prepared with White 900 g Use: Used in the treatment of psoriasis and other scaly Soft Paraffin BP) skin conditions as the coal tar in the preparation has anti-inflammatory. Zinc and Salicylic Acid Paste BP also called Non-ionic Emulsifying Ointment (Lassar's Paste) (BP 1988. Coal Tar BP 60 g if the Cetomacrogol Emulsifying Wax BP is replaced by Zinc Oxide BP 60 g Emulsifying Wax BP. Simple Ointment BP (Ung Simp) (BP 1988. Use: A suitable base into which can be incorporated active ingredients. easy (White's Tar Paste) (BP 1988.254 | Product formulae Cetomacrogol Emulsifying Ointment BP. (BP 1988. Ointments and pastes | 255 Methyl Salicylate Ointment BP Salicylic Acid Ointment BP (Ung Acid Salicyl) (Unguentum Methylis Salicylatis) (BP 1988. particularly useful for application to the scalp or as a soap substitute. Ingredients Quantities Zinc Oxide BP 150 g Simple Ointment BP 850 g Use: Used to treat nappy and urinary rash and Coal Tar Paste BPC (Pasta Picis Carbonis) eczematous conditions. Traditional 'drawing' ointment. (BPC 1973. . Oily Cream BP 940 g page 715) Use: Used to treat acne. page 868) Ichthammol Ointment BP (Unguentum Ichthammolis) (BP 1980. Liquid Paraffin BP 200 g Use: A water-miscible ointment base. page 763) Ingredients Quantities Salicylic Acid BP 30 g Precipitated Sulphur BP 30 g Zinc Ointment BP (Ung Zinc) (BP 1988. Salicylic Acid and Sulphur Ointment BPC (Ung Acid Salicyl et Sulph) (BPC 1973. sun block. Also forms an effective Use: Mild antibacterial and anti-inflammatory. page 767) Ingredients Quantities Strong Coal Tar Solution BP 75 g Compound Zinc Paste BP 925 g Use: Used in the treatment of psoriasis. Use: Used as a rubefacient to relieve pain in lumbago. page 700) Ingredients Quantities Ingredients Quantities Zinc Oxide BP 250 g Starch BP 250 g Wool Fat BP 450 g White Soft Paraffin BP 500 g Yellow Soft Paraffin BP 450 g Ichthammol BP 100 g Use: Used to treat nappy and urinary rash and eczematous conditions. ringworm and eczema. page 707) Ingredients Quantities Emulsifying Ointment BP (Ung Emulsif) (BP 1988. Compound Zinc Paste BP (Co Zinc Paste) (BP 1988. Hydrous Wool Fat BP 250 g Dose: Apply two to three times a day. sciatica and other rheumatic conditions. page 707) Cetrimide BP 30 g Cetostearyl Alcohol BP 270 g Ingredients Quantities White Soft Paraffin BP 500 g Emulsifying Wax BP 300 g Liquid Paraffin BP 200 g White Soft Paraffin BP 500 g Use: Used as an antiseptic ointment. page 713) page 712) Ingredients Quantities Ingredients Quantities Salicylic Acid BP 20 g Methyl Salicylate BP 500 g Wool Alcohols Ointment BP 980 g White Beeswax BP 250 g Use: Used to treat acne. Cetrimide Emulsifying Ointment BP (Unguentum Cetrimidi Emulsificans) (BP 1988. . 5 g Use: Each dose of 8. 2 Powder Anhydrous Glucose BP 36. of dyspepsia.5 g Sodium Bicarbonate BP 2. . recently boiled and cooled water to make a solution Use: Used as a saline purgative.08 g is usually packed separately in Dose: One of each powder. also known as Seidlitz Powder) 257 Magnesium Trisilicate Powder Compound BP (Pulvis Magnesii Trisilicatis Compositus) 257 Compound Sodium Chloride and Dextrose Oral Powder BP (per powder) 257 Effervescent Powder Compound BPC (Pulvis Oral Rehydration Salts Formula A BP Effervescens Compositus. Ingredients Quantities Ingredients Quantities No. page 874) Powder) (BPC 1973. Dissolve powder 1 in a an individual amber glass jar or plastic pot. stir and dose of this powder is dissolved in 200 mL of take while the mixture is still effervescing. Add powder 2. Each tumblerful of cold water. also known as Seidlitz (BP 1988.5 g Sodium Bicarbonate BP 1. 1 Powder Sodium Chloride BP 1g Sodium Potassium Tartrate Powder BP 7. page 710) (Pulvis Magnesii Trisilicatis Compositus) (BP 1988. page 776) This formula is sufficient to prepare 1 litre of solution. used for rehydration and electrolyte replacement in the treatment of diarrhoea.19 Powders Effervescent Powder Compound BPC Oral Rehydration Salts Formula A BP 257 (Pulvis Effervescens Compositus.4 g Tartaric Acid Powder BP 2. page 873) Ingredients Quantities Ingredients Quantities Sodium Chloride BP 500 mg Sodium Bicarbonate BP 750 mg Chalk Powder BP 250 g Potassium Chloride BP 750 mg Heavy Magnesium Carbonate BP 250 g Dextrose BP 20 g Magnesium Trisilicate BP 250 g Use: Each powder is dissolved in 500 mL of recently boiled Sodium Bicarbonate BP 250 g and cooled water to make a solution used for Dose: 1–5 g mixed with a little water between meals.5 g Potassium Chloride BP 1.5 g No. rehydration and electrolyte replacement in the Use: Used as an adsorbent and antacid in the treatment treatment of infantile diarrhoea. Compound Sodium Chloride and Dextrose Oral Magnesium Trisilicate Powder Compound BP Powder BP (per powder) (BP 1980. . Sodium Bicarbonate Ear Drops BP (Auristillae Menthol and Eucalyptus Inhalation BP (Vapor Sodii Bicarbonatis) (BP 1988.20 Miscellaneous formulae Ephedrine Nasal Drops BPC Menthol and Eucalyptus Inhalation BP (Naristillae Ephedrinae) 259 (Vapor Mentholis et Eucalypti) 259 Sodium Bicarbonate Ear Drops BP (Auristillae Sodii Zinc Sulphate and Zinc Chloride Mouthwash BPC Bicarbonatis) 259 (Collutorium Zinci Sulphatis et Zinci Chloridi) 260 Compound Sodium Chloride Mouthwash BP Chloroxylenol Solution BP (Liquor Chloroxylenolis) 260 (Collutorium Sodii Chloridi Compositum) 259 Ephedrine Nasal Drops BPC (Naristillae Compound Sodium Chloride Mouthwash BP Ephedrinae) (BPC 1973. .5 g Sodium Chloride BP 15 g Sodium Chloride BP 0. page 577) Ingredients Quantities Ingredients Quantities Sodium Bicarbonate BP 5g Light Magnesium Carbonate BP 70 g Glycerol BP 30 mL Menthol BP 20 g Water to 100 mL Eucalyptus Oil BP 100 mL Water to 1000 mL Use: Used for the softening and removal of ear wax. page 670) Mentholis et Eucalypti) (BP 1980. Dose: Add one teaspoonful to a pint of hot (not boiling) water and inhale the vapour. page 757) (Collutorium Sodii Chloridi Compositum) (BP 1988. Double Strength Chloroform Water BP 500 mL Water to 1000 mL Dose: Use approximately 15 mL diluted with an equal volume of water each morning and night. page 703) Ingredients Quantities Ephedrine Hydrochloride BP 0. Use: Used as a nasal decongestant.5 g Sodium Bicarbonate BP 10 g Water to 100 mL Concentrated Peppermint Emulsion BP 25 mL Use: Used as a nasal decongestant. Use: Used to cleanse and freshen the mouth.5 g Ingredients Quantities Chlorbutol BP 0. 6 g Zinc Chloride BP 10 g Oleic Acid BP 7. page 879) Chloridi) (BPC 1973.0 g Zinc Sulphate BP 20 g Potassium Hydroxide BP 13. page 756) Ingredients Quantities Ingredients Quantities Chloroxylenol BP 50.0 g Compound Tartrazine Solution BP 10 mL Terpineol BP 100 mL Double Strength Chloroform Water BP 500 mL Ethanol 96% (IMS is suitable) 200 mL Water to 1000 mL Purified water freshly boiled and cooled to 1000 mL Dose: This preparation should be diluted with 20 times Use: Antiseptic for skin. its own volume of water before use. Use: Used as an astringent mouthwash.5 mL Dilute Hydrochloric Acid BP 10 mL Castor Oil BP 63.260 | Product formulae Zinc Sulphate and Zinc Chloride Mouthwash Chloroxylenol Solution BP (Liquor BPC (Collutorium Zinci Sulphatis et Zinci Chloroxylenolis) (BP 1988. . in a small respiratory tract by inhalation. glycerine. ingredients in the correct Drops A liquid preparation in which the proportions. this term is enclose solids. liquids and hard capsules to Emulsion As a preparation. Draught A liquid oral preparation of fairly Granules A dry preparation in which each small volume and usually granule consists of a mixture of the consisting of one dose. The internal use. or it may be a solid . ear or volatilisation. lining of the throat. Soft nauseous medicaments. Drops may comprise an The active principle may be oral preparation (usually vapour when it is obtained from a paediatric). Dusting powder A preparation consisting of one or Bougie (nasal) A solid dosage form intended for more substances in fine powder insertion into the nostril. Elixir An aromatic liquid preparation Cachet An oral preparation consisting of including a high proportion of dry powder enclosed in a shell of alcohol.g. propylene rice paper. or may be intended for liquid preparation by introduction into the nose. the title of the product is intended for application to the amended accordingly. pipette). insertion into the urethra. intended for Douche (nasal) A liquid preparation intended for the treatment of the membranous introduction into the nostril. usually in introduction into the vagina. Douche A liquid preparation intended for Gargle An aqueous solution. quantity to be used at any one time Inhalation A preparation in which the active is so small that it is measured as a principle is drawn into the number of drops (e. and Capsule An oral preparation consisting of a intended for the oral medicament enclosed in a shell administration of potent or usually of gelatin basis. administration. in a small gelatin capsules are used to enclose dose volume. skin. emulsion may be an oil-in-water Enema An aqueous or oily solution or (aqueous creams) or a water-in-oil suspension intended for rectal type (oily creams). glycol or other solvent. generally restricted to an oil-in- Cream A semi-solid emulsion intended for water preparation intended for application to the skin. intended for the application to Bougie (urethral) A solid dosage form intended for intact skin.Appendix 1 Glossary of terms used in formulations Application A liquid or semi-liquid preparation eye. concentrated form. which Pessary A solid dosage form intended for is administered in small dose insertion into the vagina for local volumes and which should be treatment. slowly in the mouth. agents. Includes nasal and of one or more medicaments in an vaginal douches.262 | Appendix 1 where a special appliance. is needed. hot. consisting of one or more . often in high proportion of sucrose or concentrated form. usually containing sucrose. friction. an aqueous vehicle. dispersed in a suitable base and Injection A preparation intended for intended for application to the parenteral administration which skin. ovoid mass. Eye lotions are lotions It may be in bulk form or intended for application to the eye. flavoured base and intended to Spirit An alcoholic solution of volatile dissolve or disintegrate slowly in medicinal substances or flavouring the mouth. may consist of an aqueous or non. inert base and intended to dissolve Linctus A viscous liquid preparation. local treatment of the Tablet A solid oral dosage form where membranous lining of the mouth one or more medicaments are and gums. Paint A liquid preparation intended for aqueous solution or suspension. intended for other sweetening agent. application to the skin or mucous Irrigation A solution intended for membranes. introduction into body cavities or Pastille A solid oral preparation consisting deep wounds. individually wrapped quantities Lozenge A solid oral preparation consisting and is intended for oral of medicaments incorporated in a administration. Syrup A liquid preparation containing a Mouthwash An aqueous solution. often an medicaments dissolved or aerosol. suspended or diffused in or systemic treatment. Mixture Liquid oral preparation consisting Suppository A solid dosage form intended for of one or more medicaments insertion into the rectum for local dissolved. Lotion A liquid preparation intended for Powder A preparation consisting of one or application to the skin without more components in fine powder. sipped and swallowed slowly Pill A solid oral dose form consisting without the addition of water. of one or more medicaments Liniment A liquid or semi-liquid intended incorporated in a spherical or for application to intact skin. compressed and moulded into Ointment A semi-solid preparation shape. usually with considerable friction Poultice A thick pasty preparation intended produced by massaging with the for application to the skin while hand. Appendix 2 Abbreviations commonly used in pharmacy aa ana of each ex aq ex aqua in water ac ante cibum before food ext extractum an extract ad/add addendus to be added (up to) fort fortis strong ad lib ad libitum as much as desired freq frequenter frequently alt alternus alternate f/ft/fiat fiat let it be made alt die alterno die every other day ft mist fiat mistura let a mixture be made amp ampulla ampoule ft pulv fiat pulvis let a powder be made applic applicetur let it be applied garg gargarisma a gargle aq aqua water gutt/ guttae drops aq ad aquam ad water up to guttae/gtt aur/aurist auristillae ear drops h hora at the hour BNF British National hs hora somni at the hour of sleep Formulary (bedtime) BP British Pharmacopoeia ic inter cibos between meals BPC British Pharmaceutical inf infusum infusion Codex inh inhalation/inhaler bd/bid bis in die twice a day irrig irrigatio irrigation c cum with liq liquor solution cap capsula capsule lin linimentum liniment cc cum cibus with food lot lotio lotion collut collutorium mouthwash m/mane mane in the morning co/comp compositus compound md more dicto as directed conc concentratus concentrated mdu more dicto use as directed corp corpori to the body utendus crem cremor cream mist mistura mixture d dies a day mitt/mitte mitte send (quantity dd de die daily to be given) dil dilutus diluted n/nocte nocte at night div divide divide n et m nocte night and morning DPF Dental Practitioners’ maneque Formulary np nomen the proper name DT Drug Tariff proprium EP European Pharmacopoeia narist naristillae nose drops et et and neb nebula spray . 264 | Appendix 2 ocul oculo to (for) the eye qds/qid quater die four times a day oculent/oc oculentum an eye ointment qs quantum sufficient oh omni hora every hour sufficiat om omni mane every morning recipe take od omni die every day rep/rept repetatur let it be repeated on omni nocte every night sos si opus sit when necessary paa parti affectae apply to the affected part sig signa let it be labelled applicandus solv solve dissolve pc post cibum after food stat statim immediately PC prescriber contacted supp suppositorium suppository po per os by mouth syr syrupus syrup PNC prescriber not contacted tds/tid ter in die three times a day pr per rectum rectally tinct tinctura tincture pv per vaginam vaginally tuss urg tussi urgente when the cough is prn pro re nata when required troublesome pess pessus pessary ung unguentum ointment pig pigmentum a paint ut dict/ud ut dictum as directed ppt praecipitatus precipitated vap vapor an inhalation pulv pulvis a powder qqh/q4h quater every 4 hours quaque hora . gov. Benzphetamine Benzfetamine ance with EC legislation.mhra. Amylobarbitone Sodium Amobarbital Sodium Angiotensin Amide Angiotensinamide Drug names Azetepa Azatepa Balipramine Depramine The following is a list of medicinal substances for Barbitone Barbital which the British Approved Names (BANs) have been Beclomethasone Beclometasone changed to match the corresponding recommended Benapryzine Benaprizine International Non-Proprietary Names (rINNs). which became effective on 1 December Benzathine Penicillin Benzathine 2003.uk/. Benztropine Benzatropine Bethanidine Betanidine BAN rINN Bismuth Glycollylarsanilate Glycobiarsol Changed from: To: Bromocyclen Bromociclen Acepifylline Acefylline Piperazine Bromodiphenhydramine Bromazine Acinitrazole Aminitrozole Buniodyl Bunamiodyl Acrosoxacin Rosoxacin Busulphan Busulfan Allyloestrenol Allylestrenol Butamyrate Butamirate Aloxidone Allomethadione Butethamate Butetamate Alphadolone Alfadolone Buthalitone Sodium Buthalital Sodium Alphaxalone Alfaxalone Butobarbitone Butobarbital Amethocaine Tetracaine Butoxamine Butaxamine Amidephrine Amidefrine Carbiphene Carbifene . BANs have been changed to match rINNs where Benzylpenicillin the names differ to achieve consistency in the names of Benzhexol Trihexyphenidyl medicines available in the UK and to ensure compli. Benorylate Benorilate copoeia 2003. The Amphetamine Amfetamine information below has been taken from the MHRA Amylobarbitone Amobarbital website: http://medicines. Bendrofluazide Bendroflumethiazide These changes were published in the British Pharma.Appendix 3 Changing substance names from British Approved Names to recommended International Non-Proprietary Names The MHRA (Medicines and Healthcare products BAN rINN Regulatory Agency) published the following informa. Changed from: To: tion in relation to the change of substance names from Aminacrine Aminoacridine British Approved Names (BANs) to recommended Amoxycillin Amoxicillin International Non-Proprietary Names (rINNs). Chlormethiazole Clomethiazole Hemiethanolate) Chlorpheniramine Chlorphenamine Dyclocaine Dyclonine Chlorthalidone Chlortalidone Eformoterol Formoterol Chlorthenoxazin Chlorthenoxazine Epioestriol Epiestriol Cholecalciferol Colecalciferol Epithiazide Epitizide Cholestyramine Colestyramine Etenzamide Ethenzamide Clamoxyquin Clamoxyquine Ethacrynic Acid Etacrynic Acid Cloguanamile Cloguanamil Ethamivan Etamivan Clomiphene Clomifene Ethamsylate Etamsylate Clorgyline Clorgiline Ethebenecid Etebenecid Clothiapine Clotiapine Ethinyloestradiol Ethinylestradiol Co-Carboxylase Cocarboxylase Ethoglucid Etoglucid Colistin Sulphomethate Colistimethate Sodium Ethopropazine Profenamine Sodium Ethosalamide Etosalamide Corticotrophin Corticotropin Ethybenztropine Etybenzatropine Coumaphos Coumafos Ethyloestrenol Ethylestrenol Cromoglycic Acid Cromoglicic Acid Ethylphenaxemide Pheneturide Crotethamide Crotetamide Etifoxin Etifoxine Cumetharol Coumetarol Fanthridone Fantridone Cyacetazide Cyacetacide Fenchlorphos Fenclofos Cyclobarbitone Calcium Cyclobarbital Calcium Fenethylline Fenetylline Cycloprolol Cicloprolol Fetoxylate Fetoxilate Cysteamine Mercaptamine Flumethasone Flumetasone Danthron Dantron Fluopromazine Triflupromazine Deoxycortone Desoxycortone Flupenthixol Flupentixol Desoxymethasone Desoximetasone Flurandrenolone Fludroxycortide Diamphenethide Diamfenetide Flurothyl Flurotyl .266 | Appendix 3 BAN rINN BAN rINN Changed from: To: Changed from: To: Carbolonium Bromide Hexcarbacholine Diazinon Dimpylate Bromide Dibromopropamidine Dibrompropamidine Carbophenothion Carbofenotion Dichlorphenamide Diclofenamide Carphenazine Carfenazine Dicyclomine Dicycloverine Carticaine Articaine Dienoestrol Dienestrol Cellacephate Cellacefate Dimenoxadole Dimenoxadol Cephamandole Cefamandole Dimepropion Metamfepramone Cephamandole Nafate Cefamandole Nafate Dimethicone(s) Dimeticone Cephoxazole Cefoxazole Dimethindene Dimetindene Cephradine Cefradine Dimethisoquin Quinisocaine Certoparin Certoparin Sodium Dimethothiazine Dimetotiazine Chlophedianol Clofedanol Dimethyl Sulphoxide Dimethyl Sulfoxide Chloral Betaine Cloral Betaine Dioxathion Dioxation Chloramine Tosylchloramide Dipenine Bromide Diponium Bromide Sodium Diphenidol Difenidol Chlorbutol Chlorobutanol Dothiepin Dosulepin Chlordantoin Clodantoin Doxybetasol Doxibetasol Chlorfenvinphos Clofenvinfos Doxycycline Hydrochloride Doxycycline Hyclate Chlorhexadol Chloralodol (Hemihydrate. Appendix 3 | 267 BAN rINN BAN rINN Changed from: To: Changed from: To: Frusemide Furosemide Methotrimeprazine Levomepromazine Gestronol Gestonorone Methsuximide Mesuximide Glycalox Glucalox Methyl Cysteine Mecysteine Guaiphenesin Guaifenesin Methylene Blue Methylthioninium Halethazole Haletazole Chloride Halopyramine Chloropyramine Methylphenobarbitone Methylphenobarbital Heptabarbitone Heptabarb Methyprylone Methyprylon Hexachlorophane Hexachlorophene Metriphonate Metrifonate Hexamine Hippurate Methenamine Metyzoline Metizoline Hippurate Mitozantrone Mitoxantrone Hexobarbitone Hexobarbital Monosulfiram Sulfiram Hydroxamethocaine Hydroxytetracaine Mustine Chlormethine Hydroxyamphetamine Hydroxyamfetamine Naphthalophos Naftalofos Hydroxyprogesterone Hydroxyprogesterone Nealbarbitone Nealbarbital Hexanoate Caproate Nicoumalone Acenocoumarol Hydroxyurea Hydroxycarbamide Nitroxynil Nitroxinil Icomethasone Enbutate Icometasone Enbutate Norbutrine Norbudrine Indomethacin Indometacin Norethynodrel Noretynodrel Iodipamide Adipiodone Noxiptyline Noxiptiline Iophendylate Iofendylate Noxythiolin Noxytiolin Iothalamic Acid Iotalamic Acid Nylestriol Nilestriol Isobuzole Glysobuzole Octacosactrin Tosactide Isoetharine Isoetarine Octaphonium Chloride Octafonium Isometamidium Isometamidium Chloride Chloride Oestradiol Estradiol Levamphetamine Levamfetamine Oestriol Estriol Lignocaine Lidocaine Oestriol Sodium Succinate Estriol Sodium Lynoestrenol Lynestrenol Succinate Lysuride Lisuride Oestriol Succinate Estriol Succinate Malethamer Maletamer Oestrone Estrone Medigoxin Metildigoxin Oxethazaine Oxetacaine Meprothixol Meprotixol Oxpentifylline Pentoxifylline Methadyl Acetate Acetylmethadol Oxyphenisatin Oxyphenisatine Methallenoestril Methallenestril Oxypurinol Oxipurinol Methallibure Metallibure Pentaerythritol Tetranitrate Pentaerithrityl Methamphazone Metamfazone Tetranitrate Metharbitone Metharbital Pentobarbitone Pentobarbital Methenolone Metenolone Pentolinium Tartrate Pentolonium Tartrate Methetoin Metetoin Phanquone Phanquinone Methicillin Sodium Meticillin Sodium Phenbenicillin Fenbenicillin Methimazole Thiamazole Phenbutrazate Fenbutrazate Methindizate Metindizate Phenethicillin Pheneticillin Methisazone Metisazone Phenobarbitone Phenobarbital Methixene Metixene Phenoxypropazine Fenoxypropazine Methohexitone Methohexital Phenyl Aminosalicylate Fenamisal Methoin Mephenytoin Phenyramidol Fenyramidol . 268 | Appendix 3 BAN rINN BAN rINN Changed from: To: Changed from: To: Phthalylsulphathiazole Phthalylsulfathiazole Sulphadimethoxine Sulfadimethoxine Pipazethate Pipazetate Sulphadimidine Sulfadimidine Pipothiazine Pipotiazine Sulphaethidole Sulfaethidole Plasmin Fibrinolysin (Human) Sulphaguanidine Sulfaguanidine Polyhexanide Polihexanide Sulphaloxic Acid Sulfaloxic Acid Polymyxin Polymyxin B Sulphamethizole Sulfamethizole Polyoxyl 40 Stearate Macrogol Ester Sulphamethoxazole Sulfamethoxazole Potassium Clorazepate Dipotassium Sulphamethoxydiazine Sulfametoxydiazine Clorazepate Sulphamethoxypyridazine Sulfamethoxypyridazine Pramoxine Pramocaine Sulphamoxole Sulfamoxole Procaine Penicillin Procaine Sulphaphenazole Sulfaphenazole Benzylpenicillin Sulphaproxyline Sulfaproxyline Promethoestrol Methestrol Sulphapyridine Sulfapyridine Promoxolan Promoxolane Sulphasalazine Sulfasalazine Pronethalol Pronetalol Sulphasomidine Sulfisomidine Proquamezine Aminopromazine Sulphasomizole Sulfasomizole Prothionamide Protionamide Sulphathiazole Sulfathiazole Psilocybin Psilocybine Sulphathiourea Sulfathiourea Quinalbarbitone Secobarbital Sulphatolamide Sulfatolamide Riboflavine Riboflavin Sulphaurea Sulfacarbamide Rolicypram Rolicyprine Sulphinpyrazone Sulfinpyrazone Salazosulphadimidine Salazosulfadimidine Sulphomyxin Sodium Sulfomyxin Sodium Salcatonin Calcitonin (Salmon) Sulthiame Sultiame Secbutobarbitone Secbutabarbital Tetracosactrin Tetracosactide Sissomicin Sisomicin Tetrahydrozoline Tetryzoline Sodium Anoxynaphthonate Anazolene Sodium Thiabendazole Tiabendazole Sodium Calciumedetate Sodium Calcium Thiacetazone Thioacetazone Edetate Thialbarbitone Thialbarbital Sodium Cromoglycate Sodium Cromoglicate Thiazesim Tiazesim Sodium Diatrizoate Sodium Amidotrizoate Thiocarlide Tiocarlide Sodium Ipodate Sodium Iopodate Thioguanine Tioguanine Sodium Ironedetate Sodium Feredetate Thiomesterone Tiomesterone Sodium Picosulphate Sodium Picosulfate Thiopentone Thiopental Sorbitan Mono-Oleate Sorbitan Oleate Thiothixene Tiotixene Sorbitan Monolaurate Sorbitan Laurate Thioxolone Tioxolone Sorbitan Monopalmitate Sorbitan Palmitate Thymoxamine Moxisylyte Sorbitan Monostearate Sorbitan Stearate Thyroxine Sodium Levothyroxine Stanolone Androstanolone Sodium Stibocaptate Sodium Stibocaptate Triacetyloleandomycin Troleandomycin Stilboestrol Diethylstilbestrol Tribavirin Ribavirin Streptonicozid Streptoniazid Trimeprazine Alimemazine Succinylsulphathiazole Succinylsulfathiazole Trimustine Trichlormethine Sulglycotide Sulglicotide Troxidone Trimethadione Sulphacetamide Sulfacetamide Tyformin Tiformin Sulphachlorpyridazine Sulfachlorpyridazine Urofollitrophin Urofollitropin Sulphadiazine Sulfadiazine Vinbarbitone Vinbarbital . Napadisylate Napadisilate Napsylate Napsilate Changed from: To: Theoclate Teoclate Besylate Besilate Tosylate Tosilate Camsylate Camsilate . Appendix 3 | 269 BAN rINN Changed from: To: Changed from: To: Closylate Closilate Vinylbitone Vinylbital Cypionate Cipionate Viprynium Embonate Pyrvinium Pamoate Edisylate Edisilate Xanthinol Nicotinate Xantinol Nicotinate Enanthate Enantate Xanthocillin Xantocillin Esylate Esilate Ethylsulphate Etilsulfate Radicals and groups Isethionate Isetionate Mesylate Mesilate The following changes in spelling apply to names for Methylsulphate Metilsulfate radicals and groups. . Bibliography Aulton M E (ed) (1988) Pharmaceutics – The Science of Matthews L G (1962) History of Pharmacy in Britain. Edinburgh. 1968) rpsgb.html. Medicines. . 1948) Constable & Co. Baltimore. 1980. E & S Dosage For Design. Pharmacy Practice. 1973) Pharmaceutical Press. Churchill Livingstone. Churchill Livingstone. 2004. Available at http://www. Last accessed July 2009. Press.uk/informationresources/museum/resources/ Pharmaceutical Press. Lippincott. London. London Practice. British Pharmacopoeia (1914. (updated every year). Cooper J W. British Pharmacopoeia (1953. Ethics and Practice – A Guide for Pharmacists. Formulary. Gunn C (1957) Tutorial Pharmacy. London British Pharmacopoeia (1885) Spottiswoode & Co. 1963. British Pharmacopoeia (2001. British Medical Accociation and Winfield A J. 2002. London. Trease G E (1964) Pharmacy in History. Richards R M E (ed) (1998) Pharmaceutical Royal Phaemaceutical Society of Great Britain. Edinburgh. J B Lippincott. Maryland. Britain. London. Formulary for Children. Information Sheets. Bailliere Tindall & Joint formulary committee (current edition).org. 1949. The Pharmaceutical Codex: Principles and Practice of Collett D M. The Pharmaceutical Press. (updated every year). Remington J P (1905) The Practice of Pharmacy. 1932. British Medical Accociation and Royal Wade A (ed) (1980) The Pharmaceutical Handbook. London. Churchill Livingstone. Gunn C (1950) Dispensing for Pharmaceutical Thompson J E (1998) A Practical Guide to Contemporary Students. Museum of the Royal Pharmaceutical Society of Great London. Cooper J W. Philadelphia. British Pharmacopoeia (1973. 1958. British National Cox. Pitman. Edinburgh. 2009) TSO. The Phaemaceutical Society of Great Britain. Wade A. Aulton M E (ed) (1990) Pharmaceutical Pharmaceutics (12th Edition) (1994) Pharmaceutical Practice. Weller P J (ed) (1994) Handbook of Pharmaceutical Joint formulary committee (current edition). London. London. 1988) HMSO. London. USA. London. London. British National Excipients. Edinburgh. 1968. London. Pitman. 1963. London. Williams & Wilkins. Royal Pharmaceutical Society of Great Britain. London (updated Pharmaceutical Press. Livingston Ltd. 1934. 1954. 1959. British Pharmaceutical Codex (1911. every six months). USA. informationsheets. . paediatrics 208. synonyms 88 Arabia. 5. wines. 98. tinctures. 263 Ammoniated Rhubarb and Soda Mixture BPC 239 when not to use 49. 249. 132. 261 alpha-tocopherol acetate 82 aquae (waters) 32 aluminium hydroxide 134 aqueous bases. 87. 211 ammonium citrate 244 Acacia BP 85. 42 alkyl gallates 82 apothecaries’ weights (for balances) 35 allergies 74. 187 Ammonia and Ipecacuanha Mixture BP 235 Aromatic Cardamom Tincture BP 30 Ammoniated Potassium Iodide Mixture BPC 239 Aromatic Magnesium Carbonate Mixture BPC 234 . 106. legislation on 7 choice for formulations 84 age. age range 208 antioxidants advertising. 150 accuracy. 226 Aluminium Powder BP see Compound Aluminium aqueous creams 153 Paste BPC aqueous phase see emulsions amaranth. balances 50 anionic surfactants 87 aceta (vinegars) 32 anise oil. 210 choice for packaging 84 aged patients 210 concentrations 84 alcohol 81 in dermatological preparations 213 in chloroform preparations 34 for emulsions 84 in concentrated infusions 25 mixing in solution 62 emulsions for external use 137 as preservatives 82 lotions 77 to prevent atmospheric oxidation 84 as preservative 81 salicylic acid as 213 scalp lotions 105 suspensions 84 solutions in 104 time of addition 84 as solvent 77 antioxygens 82 see also named alcohols. 240 Apothecaries Act (1815) 5 Alkaline Gentian Mixture with Phenobarbitone BPC 236 apothecaries’ system. 127. weights and measures 41. 164 Ammonium Chloride Mixture BP 108. in Concentrated Anise Water BP 34 acid honeys see oxymels Antidotarium Nicolai (Salernitanus) 8 adolescents.Index abbreviations 41. 138. 140 ammonium soaps 138. 112 Arachis Oil BP 141. 209. 77. wool antisepsis 66 alcohols apothecaries 4. creams 160 arachis oil 77 amber medicine bottles 96. 56 Ammonium Chloride and Morphine Mixture BP 243 absorption bases 79. 8 amber glass jars. suppositories 80 Aluminium Hydroxide and Belladonna Mixture BPC 235 Aqueous Cream BP 159. 97. 241 absorption of drugs 116. ancient 4. 89 applications 92. 42 alginates 168 see also Society of Apothecaries Alkaline Gentian Mixture BP 106. 169 bronopol 82 benzalkonium chloride 81 Buffered Cream BP 226 benzoic acid 27. 52 moulds 18. suppositories 80 British Pharmaceutical Codex 3. of Malaga. 53. Ibn al. foundation of Pharmaceutical Society of Great suppositories 183 Britain 6 Water for Injections BP 77 Belladonna and Ephedrine Mixture Paediatric BPC 243 editions 13. 52. Salicylic Acid BP in 176 asthma 77 biscuit porcelain 26 atmospheric oxidation. 14 Belladonna and Ipecacuanha Mixture Paediatric BPC 243 entries from European Pharmacopoeia 75. 214 definitions suppositories and pessaries 80 creams 153 mould calibration 185 of freshness 113 water-soluble 79 ointments 163 see also absorption bases. 163. neonates 210 weights and measures 235 body surface area 210.. 15 emulsifying 79. 164 British Pharmacopoeia 13. total. 97 viscous liquids 40 Baitar. as preservative 84 Bergmann. 81 buffers 83. 134. changing to rINNs 265 aqueous. antioxidants to prevent 84 bismuth subgallate 191 atropine bitter taste. Class B balances pessaries 184 beeswax 78. 43 oils 40 avoirdupois weights 41. vehicles oral emulsions 131 beakers 58. 137 purified water 77 Bell. 54. 75 for ointments 77. 42 poisons 39 see also pounds (imperial) tablets 96. flavourings to mask 90 formulations containing 245 blood–brain barrier. body water.. infants 209 aural bougies 19 borate buffers 85 auxiliary labels 92. amounts 135 benzyl alcohol 81 aromatic waters 21 Benzyl Benzoate Application BP 249 ascorbic acid. Jacob. Torbern (18th-century chemist) 10 Association of Chemists and Druggists 5 Betnovate Ointment. 76 Belladonna Mixture Paediatric BPC 233 metric system 13 Belladonna Tincture BP on potable water 76 formulations containing 235. 84 Benzoic Acid BP 117 bulk liquid containers 40 . as emulsifying agents. 55 definitions 261 Class B 51. 19 portable steelyards 35 nasal 19 skills 50 urethral 19 weight ranges and scale increments 51 boxes weights greater than 50 g 55 pills 28 see also beam balances suppositories 69 Baltimore Paste (Compound Aluminium Paste BPC) 166 see also cartons bases British Approved Names. 245 British Society for the History of Pharmacy 17 Bentonite BP 86. Corpus of Simples 4 see also medicine bottles balances bougies 18 choice 55 aural 19 Class II 51.274 | Index aromatic oils. 95 bottles 39 avoirdupois measures 41. 104 oral solutions 102 beam balances 36 oral suspensions 115 see also Class II balances. 211 see also entries beginning Belladonna. 54. manual 72 chlorbutol 82 counting equipment 69. 225 Cetrimide Emulsifying Ointment BP 254. 185. 255 centralisation. 229 method of preparation 201 chlorocresol 81. . protective 66 cellulose derivatives 168 coal tar 155. 234 machines 19 Chalk with Opium Mixture Aromatic BP 243 Calamine and Coal Tar Ointment BP 171. Index | 275 bulk powders 196. 205 Cetomacrogol Cream BP 226 butyl hydroxybenzoate 81 Cetomacrogol Emulsifying Ointment BP 254 butylated hydroxyanisole 82 Cetostearyl Alcohol BP 78 butylated hydroxytoluene 82 cetrimide 82 Byzantine area 4 Cetrimide Cream BP 156. 187 child-resistant closures 96 camphor. in Paediatric Chalk Mixture BP 123. 53. 117 packaging 205 chloroform 11. 55 see also boxes Class B balances 51.’ 94 cannabis (Extract of Cannabis BPC) 21 see also paediatrics capsules 200 chip boxes 40 auxiliary labels and expiry dates 92 Chirurgerye (Vigon) 8 capacities vs sizes 201 Chloral Elixir Paediatric BPC 245 contents for children 209 Chloral Mixture BP 243 counting. 197. Concentrated Camphor Water BP 34 children Camphorated Opium Tincture BP. The’ (engraving) 35 Calamine Lotion Oily BP 250 chemists Calamine Ointment BP 253 abandonment of register 7 calcium carbonate 235 legislation restricting 6 calcium soaps 137 origins 5 calibrated containers for liquid preparations 97 ‘pharmaceutical’ (title) 6 calibration. suppository moulds 69. 82 capulae amylaceae see cachets Chloroform Water BP 22 caramel 88 see also Double Strength Chloroform Water BP carbomer 86. 184. 254 chelating agents 84 Calamine Cream Aqueous BPC 226 chemical incompatibilities 213 Calamine Lotion BP 250 ‘Chemical Lab. 84. 168 chlorophyll 88 carboys 40 Chloroxylenol Solution BP 260 cardamom 30 chlorpromazine 246 cardboard boxes 40 cinnamon. terminology 208 Camphorated Opium Mixture BPC 239 ideal weights and body surface areas 211 Cancer Act (1939) 7 ‘Keep out of the reach of. 52. . 94 Cationic Emulsifying Ointment BP see Cetrimide Clioquinol Cream BPC 227 Emulsifying Ointment BP Clobazam 126 cationic surfactants 87 Clostridium tetani. 98 Class II balances 51. in Compound age ranges. 213. 255 cachets 19. 52 Cascara and Belladonna Mixture BPC 235 clays 86. 254. 171. Bentonite BP 86 CCS & S ointment 174 clothing. 74 chlorhexidine 82 definitions 261 Chlorhexidine Cream BPC 227 emergency suspensions from 117 Chlorhexidine Dusting Powder BP 196. balances 52 cocaine 246 . 74. for Chalk Mixture Paediatric BP 124 carmellose sodium 168 citric acid 63. 160. 134. 90 carmine 88 see also sodium citrate cartons 93. 169 catechu (Infusion of Catechu BP) 23 cleanliness 66. 261 chalk. emulsion. medicine bottles 96 Compound Zinc Paste BP 177. as ingredient 257 Confectio de Hyacinthi 9 DIAL (Drug Information Advisory Line) 208 confections 20 Diamorphine and Cocaine Elixir BPC 246 conical measures 57 Diamorphine. Nicholas (1616–1654). 89. 34 decoction(s) 20 Concentrated Cinnamon Water BP. for Chalk Mixture Decoction of Chondrus BPC 20 Paediatric BP 124 demijohns 40 Concentrated Compound Gentian Infusion BP 24 demy paper 72 concentrated infusions 23 dermatological formulation 213 Concentrated Peppermint Emulsion BP. Cocaine and Chlorpromazine conserves 20 Elixir BPC 246 containers 96 Diamorphine Linctus BPC 247 contamination diazepam. 56 collodions 20. 127 curved sides. 155 Compound Sodium Chloride and Dextrose Oral incorporation of solids 154. 204 continuous phases. 106.276 | Index cochineal 88 clays 86 Cod Liver Oil. 155 Powder BP 257 preparation 154 Compound Sodium Chloride Mixture BPC 240 cresol 81 Compound Sodium Chloride Mouthwash BP 109. Physicall Directory 12 Compound Tragacanth Powder BP 86. fats 132 . Poisons and Pharmacy Act (1908) 6 Compound Benzoic Acid Paste BP 253 Corpus of Simples (Ibn al Baitar) 4 Compound Bismuth Subgallate. 196 Codeine Linctus BPC 245 tablet counters 74 Codeine Linctus Paediatric BPC 246 Continental method see dry gum method Codeine Phosphate BP 186. 50. 136. rectal 209 avoidance 67 diffusible suspensions 116 see also cleanliness. emulsions 131 Colchicum and Sodium Salicylate Mixture BPC 236 conversions 45–46 cold water infusions 22 metric 49. paediatrics 208 copper sulphate. topical 209. emulsions 136 Compound Camphorated Opium Mixture BPC 239 creaming 87. suppositories 191 corticosteroids. 213 Compound Calamine Application BPC 251 counting equipment 69. 137 Compound Cardamom Tincture BPC 30 creams 153 Compound Gentian Tincture BP 31 auxiliary labels and expiry dates 92 Compound infusion of horseradish 23 bases 214 Compound Magnesium Trisilicate Oral Powder BP 202 definitions 261 Compound Rhubarb Mixture BPC 239 formulae listed 225 Compound Rhubarb Mixture Paediatric BPC 239 incorporation of liquids 154. 44 comminution 36 Copper and Zinc Sulphates Lotion BPC 250 community pharmacy. suppositories 186 Companion to the British Pharmacopoeia (Squire) 13 Corbyn quart bottle 40 Compound Aluminium Paste BPC 166 corporates. 255 Concentrated Anise Water BP 34 Dalibour Water 250 Concentrated Camphor Water BP 34 Dark Ages 4 Concentrated Chloroform Water BPC 33. 259 Crown and Anchor Tavern 6 Compound Tolu Linctus Paediatric BPC 247 Culpeper. 88. 117 traditional vs metric 42. for Arachis Dermovate Cream 159 Oil BP 141 dextrose. hygiene digestion. magistral formula 138 dusting powders 195. 214 traditional to imperial 44 colourings 87. 74 Compound Calcium Carbonate Mixture counting triangles 72 Paediatric BPC 235 cracking. British Pharmaceutical Codex 15 expiry dates 92 drops formulation 133 definition 261 metrication 44 paediatric 105 problems 136 . 138 doubling up technique 118 emulsions 131. emulsions 131 Effervescent Powder Compound BPC 257 displacement values. 123. 261 antioxidants for 84 drachms 41. 195. suppositories 185 effervescents see tartaric acid disposable plastic suppository moulds 69 Egypt. 109. 229. nasal drops diluent directories 159. for weights 52 definition 261 dressings. Edinburgh Pharmacopoeia (1783) 12 see also ear drops. 117. 63 Dublin Pharmacopoeia 3. 11 of moulds 193 EDTA 84 disperse phases. checking of weighing 52 dithranol 180. Ancient 3 dissolution 62 elderly patients 210 factors affecting rates 103 electric hotplates 74 methods 104 electrolytes. 68 Sodium Bicarbonate Ear Drops BP 259 legislation 7 Edinburgh Pharmacopoeias 3. 12 Dimethicone Cream BPC 225 dusting powders 92. Ferrous Sulphate Mixture BPC packaging 205 235. Emulsifying Ointment BP 254. 198 dry extracts 21 dry gum method 136 dry gum method 133. 88. 196. 104. 261 geriatric patients 211 emergencies. 73 salts 104 electronic counters 73 distribution (pharmacokinetic) electuaries 20 children 209 elixirs 92. paraffin bases for 78 dilution ratios 23. 142. 213 drug addiction. tolerance 207 dilution druggists 5. 139. 135 small quantities 55 dry-seal cachets 20 topical corticosteroids 213 dry skin. 42 auxiliary labels 92 draughts 105. 261 bottles for 40 drawers. 261 discard dates see expiry dates labelling 206 discoloration. 244 disodium edetate 84 ear cones 19 Dispensatorium (Cordus) 8 ear drops dispensing auxiliary labels and expiry dates 92 extemporaneous 65. 55. Oral Rehydration Salts Formula A BP 257 more than one solute 62 electronic balances 54. 6. 7 calculations 63. 164 Double Strength Chloroform Water BP 106. Index | 277 digitalis. powders 198 preparations for external use 137 double maceration 24. 255 121. 146 emulsifying waxes 87. 133. 25 emulsifying bases 79. 133 doses calculation of amounts 134 checking 208. 211 hydrophil–lipophil balance 134 frequency 212 hydrophilic 134 measurement 43 lipophilic 134 see also posology oil-in-water emulsions 138 double dilution calculations. 132 douches 105. 213 emplastra see plasters dodecyl gallate 82 emulsifying agents 87. ointments 164 expiry dates 91. 90. measures flavourings 88. 114. 98. Claudius. classification of see also magistral formulae balances 51 Frederick II (king of Germany) 4 European Pharmacopoeia. 112 auxiliary labels 92 dose checking 212 expiry dates 92. 259 emulsions 133 Europe. 261 gels.278 | Index ratio of oily to aqueous phase 135 see also dusting powders stability 136 Extract of Cannabis BPC 21 volume calculations 135 extracts 21 see also oil-in-water emulsions eye discs 21 enemas 92. tinctures. 68 Gelatin BP 167. counting equipment. 95 Belladonna and Ipecacuanha Mixture Galen. protective equipment fluid ounces 41. 76 Fresh Acid Infusion of Rose BPC 24 excipients in pills 27 ‘Freshly Prepared’ emulsions 151 excretion of drugs ‘Freshly Prepared’ solutions 113 geriatric patients 211 fs (symbol) 42 paediatrics 210 fusion. 105. 89 see also balances. mediaeval 4 skills 49 European Economic Community. products 74 ethyl hydroxybenzoate 81 formulation eucalyptus. 200 suspensions 128 see also capsules extemporaneous dispensing 65. 114. entries in British frequency of doses 212 Pharmacopoeia 75. 89. infants 209 solutions 112 Gee’s Linctus (Linctus Squill Opiate BPC) 248 suppositories and pessaries 193 gelatin 19. of Pergamum (131–201) 18 Paediatric BPC 243 galenicals 18 creams 160 gallon (Roman) 36 emulsions 151 gargles 92. 168. wines formulae. 91. 42 equivalent weights 60 fluted amber medicine bottles 97. 167. 188 dermatological 213 gelling agents 167 external preparations 105 gels 167 containers for 97. 92. pastes and ointments 181 gastric emptying time. 134 required 67 flavoured syrups 29. 105. 112 ethanol see alcohol. in Belladonna and ointment bases 79 Ephedrine Mixture Paediatric BPC 243 Ferric Ammonium Citrate Mixture BPC 244 Ephedrine Nasal Drops BPC 259 Ferric Ammonium Citrate Mixture Paediatric equipment BPC 244 extemporaneous dispensing 67 Ferrous Sulphate Mixture BPC 244 historical 34 Ferrous Sulphate Mixture Paediatric BP 235 listed 17 fixed oil bases 79. 98. infants 209 powders and capsules 205 gastric pH. 181 emulsions 137 general method 169 labelling 95 labelling 181 metrication 43 packaging 181 suspensions 120 preservatives 169 . 92 (vessels). 261 English Glassware in the 17th Century (Thorpe) 38 fats 163 Ephedrine Elixir BPC 246 digestion 132 Ephedrine Hydrochloride BP. in Menthol and Eucalyptus Inhalation BP dusting powders 196 125. recommended Hippocrates (of Kos) 3 (rINN) 265 . 125. ‘Gripe Mixture’ 245 avoirdupois weights gum resins 29 incompatibilities 212 index to formulae 219 hair. secretary of Pharmacopoeia packaging 205 Commission 14 industrial methylated spirits 77. displacement value 185 medicine bottles 39 Hydrocortisone Cream BP 227 pestles and mortars 68 hydrophil–lipophil balance (HLB) 134 phials 38 hydrophilic emulsifying agents 134 glasses. hygiene 66 infants hard capsules 201 age range 208 Hard Fat BP 80 gastric emptying time 209 Hard Paraffin BP 78 total body water 209 Hawes Bill 5 information. MP 7 Compound BPC 236 graduations. 259.H. paediatrics 208 Phenobarbitone BPC hotplates. 214. symbol for 42 individual unit dose powders 197. 233. electric 74 geriatrics 210 humectants 169 glass hydrocarbon bases 78. 14 homogenizers 149 gentian. topical absorption 209 inspissated juices 21 Hexachlorophane Dusting Powder BPC 229 International Non-Proprietary Names. need for glass 36 hypersensitivity. 154 hands. 226 Great Antidote of Matthiolus 9 Ichthammol Ointment BP 255 Greece. honeys. acid see oxymels 240–241 hospital formulae. ideal. asthma 77 Henry VIII (King) 5 insolubility 212 hexachlorophane. weighing 53 Ichthammol BP 189. bougies 19 hygiene. 106. paediatric posology 208 from mixing 136 infusion(s) 22 preparation of creams 154 Infusion of Catechu BP 23 supplies 74. colorants 89 granules. on labels 94 heat information sources. 187 hyoscyamus. 236. safety precautions 66 indiffusible suspensions 116 half. 75 Infusion of Valerian BPC 23 suppository preparation 186 inhalations 92. formulations containing 24. 198–199 hamamelis (Liquid Extract of Hamamelis BPC) 21 Codeine Phosphate BP 204 Hampshire. 120. magistral formulae from 126 see also Alkaline Gentian Mixture with hospital pharmacy. in Magnesium Trisilicate and Belladonna Glycerite of Tar 22 Mixture BP 245 glycerol 77. personal 66 glycerins 22 hyoscine. safety 66 hydrophilic ointment bases 164 Glycerin Suppository BP 80 hydroxybenzoates 81 glycerinated gelatin. (Dr). weighing and measuring 41 General Medical Council 13. Index | 279 Gelsemium and Hyoscyamus Mixture Compound historical aspects 3. William. 82. The 8 imperial system see avoirdupois measures. 8 BPC 236 historical equipment 17 General Association of Chemists and Druggists 5 historical systems. in Gelsemium and Hyoscyamus Mixture Glyn-Jones. vs weights 211 insecticides. 164 measures 36 Hydrocortisone BP. Ancient 3 immiscibility 212 Grete Herball. C. definition 261 greasy products. 137. 261 heights. Oxford Street pharmacy 35 liquid(s) juices 25 calibrated containers for 97 incorporation in creams 154. 145 Latin. 248. 137 maceration 24. 238. 262 lamellae (eye discs) 21 lozenges 25. Dublin Pharmacopoeia 3. balances 52 irons. 160 see also hydrophil–lipophil balance John Bell. 12 levelling. 138.280 | Index International Pharmacopoeia 3. 29 Lassar’s Paste (Zinc and Salicylic Acid Paste BP) macrogols 79. 23. 245 incorporation in ointments 165 labelling 95 labels/labelling 66. 105. 262 lanolin 79. 116. specific Acts Ireland. 208 Isoniazid Elixir BPC 247 Linctus Squill Opiate BPC 248 isopropyl alcohol 81 linctuses 92. labels 94 ipecacuanha. plaster-making 28 levigation 154. 114 derivative works 3. 25. 105. use of 42 lipophilic emulsifying agents 134 jars 15. 164 213. 262 ‘j’ (character). 155 kaolin. 92. 58 auxiliary 92. 127. 262 isotonicity 60 see also specific formulations liniments 92. 249. 186 irrigations. 8 positioning 91 second edition (1650) 9 Potassium Permanganate Solution 111 third edition (1677) 9 powders 206 fourth edition (1721) 10 security 94 fifth edition (1746) 10 Sodium Chloride Compound Mouthwash BP 109 sixth edition (1788) 10 solutions 113 seventh edition (1809) 11 storage instructions 91 eighth edition (1824) 11 suppositories 193 ninth edition (1836) 11 suspensions 129 tenth edition (1851) 11 warning labels 95. 236. for pharmacopoeias 11 from hospital formulae 126 . 165. definition 262 licensing 207. 249. 91 measuring 55. 244 see also Medicines Act (1968). formulations containing 241. legislation 6 243. 95 paediatric preparations 209 capsules 206 taring of containers 97 Chalk Mixture Paediatric BP 123 weighing 54 cleanliness 94 see also viscous liquids Clobazam 126 Liquid Extract of Hamamelis BPC 21 Cod Liver Oil emulsion 138 Liquid Extract of Liquorice BPC 22 creams 161 Liquid Paraffin BP 78 emulsions 152 magistral formula 145 gels 181 Liquid Paraffin Emulsion BP 148 information on 94 sodium saccharin trituration for 148 Magnesium Trisilicate Mixture BP 120 liquorice (Liquid Extract of Liquorice BPC) 22 medicine bottles 96 litres 55 ointments 181 Lobelia and Stramonium Mixture Compound BPC 238 pastes 181 London Pharmacopoeia pessaries 193 first edition (1618) 3. 15 legibility. 12 dusting powders 206 Lotio Rubra (Zinc Sulphate Lotion BP) 250 Lactose BP 197 lotions 77. 254 magistral formulae 75. 141. 111. 105. formulations containing 235. as emulsifying agents 135. 168 mucous membranes. Sir Theodore de 9 milliequivalents 60 measures (vessels) 56. 184. 98. 44 Magnesium Sulphate Mixture BPC 234 imperial system and. tablets and capsules 72 milk 133 Mayerne. on British Pharmacopoeia 14 viscous liquids 104 Medical Council Act (1862) 13 see also immiscibility Medical School of Salerno 8 mixtures medicated syrups 29 auxiliary labels and expiry dates 92 medicated vinegars 32 definition 262 medicine bottles 15. 67 parallax errors 58 making solutions 104 taring of bottles 98 matching 69 use in measuring 57. 187 geriatric patients 211 mouthwashes 105 metals auxiliary labels and expiry dates 92 London Pharmacopoeia. 93. 257 weighing 49 manual counting. Index | 281 Magnesium Carbonate Mixture BPC 233 conversions 49. 56 magnesium hydroxide 134 from/to traditional 42. 87. 95 in Ipecacuanha and Morphine Mixture BPC 244 Mel Depuratum 26 in Kaolin and Morphine Mixture BP 245 melting 74 Morphine and Cocaine Elixir BPC 246 meniscus mortars and pestles 37. 97. 42 liquids 58 Ministry of Health Act (1919) 7 safety procedures 66 mixing skill 55 antioxidants 62 mediaeval Europe 4 dry gum method 136 Medical Act (1858) 13 in mortars and pestles 62 Medical Act (1950). 186. 202. 259 suppository moulds 69 definition 262 Methadone Linctus BPC 248 warning labels 114 methyl hydroxybenzoate 81 Zinc Sulphate and Zinc Chloride Mouthwash BPC Methyl Salicylate Ointment BP 255 260 methylated spirits. 112 for internal use. 96. 58 methods of use 68 menstrua see solvents mixing powders 62 Menthol and Eucalyptus Inhalation BP 125. 137 disadvantage of solutions 102 minims 41. 50. solutions for application to 63 metric system Museum of the Royal Pharmaceutical Society 15 British Pharmacopoeia 13 Myrrh Resin BP 29 . 245. for flavouring 91 Most Excellent Homish Apothecary (Brunschweig) 8 mercurials 81 moulds Mesopotamian civilisations 3 bougies 18. 57 millimoles 59. volume units 56 241. 60 external preparations listed 95 moles 59 fluted bottles 97 morphine on labelling 94. 60 measuring 37 mineral oils. 154 mucilages 26 methylcellulose 86. 73. 259 porcelain 68 Menthol BP. third edition (1677) 10 Compound Sodium Chloride Mouthwash BP 109. 19 metabolism of drugs dispensing of 193 children 210 suppositories 69. 137. formulae listed 231 Medicine Stamp Act (1812) 7 oral 105 Medicines Act (1968) molecular masses 59. industrial 77. 185. formulations containing 120. posology 43 magnesium trisilicate. 181 age ranges. 99. 197 protein binding 210 packaging 205 topical absorption 209 emulsions 131 New London Dispensatory (Salmon) 12 metrication 43 non-emulsified absorption bases 164 paediatric 209 Non-ionic Emulsifying Ointment BP 254 solutions 104 non-ionic surfactants 87 suspensions normal saline 60 diffusible 118 numbers. in children 209 blood–brain barrier 210 oral preparations excretion of drugs 210 bulk powders 196. 72 ideal weights and body surface areas 211 old patients 210 paints. labels 95.282 | Index names of drugs. 96 indiffusible 119 Nuremberg Pharmacopoeia 8 Oral Rehydration Salts Formula A BP 257 nux vomica 236 Orange Peel Infusion Concentrated BPC 24 Nux Vomica Mixture Acid BPC 238 osmotic pressures 60 Nux Vomica Mixture Alkaline BPC 238 overages 103 overdosing 212 oblata see cachets Oxymel BPC 26 obsolete preparations 17. 160 powders 197. 18 oxymels 26 octyl gallate 82 ‘off-label’ use. 112. changing from BANs to rINNs 265 online material 19 names of patients. 253 Paediatric Chalk Mixture BP 123. definition 262 oleic acid 138 palliative care. for children 208 packaging official formulae 74 choice of antioxidant 84 oil(s) 77. tolerance to opioids 207 oleo resins 28 paper Olive Oil BP 79 capsule preparation 201 . ratio to aqueous phase 135 emulsions 151 see also fixed oil bases gels. 133 suppositories and pessaries 193 emulsifying agents 138 suspensions 128 oily creams 153 see also containers ointment(s) 163. terminology 208 general method 164 drops 105 weighing 53 formulations 207 ointment bases 77. 234 auxiliary labels 92 Paediatric Opiate Ipecacuanha Mixture BPC 238 definition 262 paediatrics expiry dates 92. on labels 94 opioids nasal bougies 19 linctuses 248 nasal drops 92. 98. 163 creams 160 emulsions. 113 oil-in-water emulsions 131. labelling 96 ointment jars 94. 163. 214 liquids. pastes and ointments 181 oil bottles 40 powders and capsules 205 oil-in-water creams 153 solutions 101. 209 ointment tiles 69. 259 tolerance 207 National Health Services Act (1946) 7 see also specific drugs National Insurance Act (1911) 7 Opium Tincture BP. in Chalk with Opium Mixture National Insurance Act (1946) 7 Aromatic BP 243 neonates Opodeldoc (Soap Liniment BPC) 249 age range 208 oral absorption. recommended books 10 phenyl mercuric acetate 81 penicillins phenyl mercuric nitrate 81 absorption in infants 209 phenytoin. 112 pestles and mortars see mortars and pestles plasters 28. Index | 283 demy 72 Pharmacopoeia committees 13 preparation of powders 199 Pharmacy Act (1852) 6 rice paper cachets 19 Pharmacy Act (1868) 6 Paracetamol Elixir Paediatric BPC 247 poisons bottles 39 paraffin bases 78. 181. Dr Henry (1746). Richard (1777–1851) 11 peppermint 90. thickening agents 86 ‘pharmaceutical tea-party’ 6 polyvinyl alcohol 169 pharmacies porcelain 68 identification on labels 94 posology 43. 262 bases 80 pill boxes 28 definition 262 pill machines 27 Ichthammol BP 189 pipettes 69. meniscus 58 phase inversion 136. 72. 91. names on labels 94 Phenobarbitone Elixir BPC 247 peanut oil 77 phenol 81 pectin 168 phenoxyethyl alcohol 81 Pemberton. suppositories 186 Pholcodine Linctus Strong BPC 248 percentage strength 61 phosphate buffers 85 percolation 29 photoelectric counters 74 see also reserve percolation process physical incompatibilities 212 perforated counting trays 73 Physicall Directory (Culpeper) 12 personal hygiene 66 physicians. 141 Pholcodine Linctus BPC 248 percentage calculations. 253 in Alkaline Gentian Mixture with Phenobarbitone pastilles. 73 moulds 73 plain amber medicine bottles 96. 164 see also Royal Pharmaceutical Society polysaccharides. 214 pH plastic ointment jars 160 gastric. origins 4 Poisons and Pharmacy Act (1908) 6 Pharmaceutical Society of Great Britain Poisons Board 7 members on Pharmacopoeia committees 13 Poisons List 6 Pharmacy and Poisons Act (1933) 7 polyethylene glycols 79. infants 209 plastic suppository moulds. 165. specific pharmacopoeias Potassium Citrate and Hyoscyamus Mixture Pharmacopoeia Commission 14 BPC 239 . solutions 63 see also official formulae. 207 see also premises see also doses pharmacopoeia(s) potable water 76 historical aspects 8 potassium citrate. status vs apothecaries 5 pessaries 183 pill(s) 27. 137 parenteral route. disposable 69 solutions 63 poisons see also buffers bottles for 39 ‘pharmaceutical chemist’ (title) 6 Dublin Pharmacopoeia on 12 pharmaceutical profession. definition 262 BPC 236 patients. absorption in infants 209 tablet counters and 74 phials 38 pepperers 4 Phillips. paediatric formulations 208 phenobarbital parts (units of strength) 61 absorption in infants 209 pastes 92. 164 Pharmacy Acts (1953 and 1954) 7 Paraffin Ointment BP 78 Pharmacy and Poisons Act (1933) 7 parallax errors. 226. 98. legislation 7 standards for record keeping 67 propyl gallate 82 on tablet counters 74 propyl hydroxybenzoate 81 see also Pharmaceutical Society of Great Britain propylene glycol 77. 262 ‘Recently Prepared’ emulsions 151 pounds (imperial) 41. 82 protective equipment and clothing 66. Pharmaceutical Society of Great Britain 6 for external use 137 Royal College of Physicians 5 gels 169 London Pharmacopoeia (1618) 8 suspensions 117 Royal Pharmaceutical Society preterm newborn infants. 213 safety. 42 ‘Recently Prepared’ solutions 113 powder trestles 199. 213. 26 weighing 53. 209 children 209 Codeine Phosphate BP 204 see also suppositories definition 262 reducing agents 84 incorporation in creams 155 refrigerators. record keeping 67 incorporation in ointments 165 rehydration. individual unit dose resins 28 powders rhubarb. Zinc Gelatin BPC 167 poultices 28. querns 36 250. pill-making 27 before modern era 34 Roman gallon 36 standards 66 Rome. 200 Recettario fiorentino 8 powders 195. Ancient 4 work areas 66 rose (Fresh Acid Infusion of Rose BPC) 24 prepared oleo resins 28 ‘Rose Case’ (1703) 5 preservatives 80. vinegar for 32 Salernitanus. 176. Oral Rehydration Salts Formula A BP for mixing 62 257 reducing 68 reserve percolation process 25. extemporaneous dispensing 65 protein binding safety glasses 66 geriatric patients 211 safety procedures for measuring 66 neonates 210 saffron 88 Pseudomonas aeruginosa. 214. Nicolaus 8 Purified Water BP 76 Salerno. 197 resinous tinctures 212 see also dusting powders. 112 premises 35 rice paper. cachets 19 control by Pharmacy and Poisons Act (1933) 7 rollers. 239 precision. 255 querying doses 212 see also sodium salicylate . Medical School 8 salicylic acid quality assurance see standards as antioxidant 213 quaternary ammonium compounds 81 formulations containing 158. age range 208 foundation 5 primary emulsions 136 Museum 15 proprietary medicines. 23 re-melting. paediatric formulations 208 emulsions 133 Royal Charter. 70. 72 calculations 198 rectal absorption for children 197. 136 Potassium Permanganate Solution 111 see also antioxidants pottery jars 15. in Ammoniated Potassium Iodide Mixture BPC 239 rancidity 79. 83 route of administration. formulations containing 233. 257 recommended International Non-Proprietary Names 265 auxiliary labels and expiry dates 92 record keeping 67. 55.284 | Index Potassium Citrate Mixture BP 234 Quillaia Tincture BPC 30 Potassium Iodide BP. balances 50 ribbed amber medicine bottles 97. 170. 259 weighing 54 sodium chloride standards for flavouring 91 extemporaneous dispensing 66 formulations containing 109. pastes 166 squill. 248 skills. William (1644–1713). insufficient 213 sour taste. 155 portable steelyards 35 incorporation in ointments 165 see also balances solubility 61. 103 scalp. 110. paraffin bases for 78 ss (symbol) 42 Sloane. dissolution Senega Infusion Concentrated BPC 25 solvents 76. dose measurement 43 skiing. 241 stomach. Gelatin BP 188 as preservative 84 steroids. flavourings to mask 90 emulsions of 134 scales (weighing) incorporation in creams 154. 103 secundum artem 17 general method 103 Seidlitz Powder (Effervescent Powder Compound general preparation 60. lotions for 105 solutions 101. paraffins 78 galenicals 18 serial dilution calculations. Index | 285 saline. formulations containing 236. 257. 239. portable 35 for flavouring 91 sterilisation. 72. formulations containing 26. 112. New London soft gelatin capsules 201 Dispensatory 12 soft soap 138 salts. topical 209 Sodium Citrate Mixture BPC 240 stirring 104 sodium metabisulphite 84 Acacia BP 140 sodium saccharin trituration. powders 198 spirits 105. Clioquinol Cream BPC 227 121. 62. 113 semi-permeable membranes 60 see also dilution. infants . 62. weights 35 spatulas 27. 262 single-dose powders see individual unit dose powders spoons. 38. Sir Hans 10 stability snuffs 29 emulsions 136 Soap Liniment BPC 249 solutions 103 soaps 138 see also expiry dates Society of Apothecaries 5 staining materials sodium bicarbonate. Peter. formulation 49 Squill Vinegar BPC skin Squire. 64. 259 premises 66 isotonic solutions 60 record keeping 67 sodium citrate steelyards. powders 198 sorbic acid 81 shaking. 236. Companion to the British broken. 103 BPC) 257 packaging 101. 202. dilution 63 240. 254 spirit levels 52 single dilution calculations. 101 sensitivity. for Liquid Paraffin stirring rods 69 Emulsion BP 148 stock bottles 40 sodium salicylate. 245. dissolution 104 solids 195 salty taste. 240. solutions for application to 63 Pharmacopoeia 13 dry. isotonic solutions 60 sodium sulphite 84 Saline Mixture BPC 233 soft extracts 21 Salmon. stock solutions. flavourings to mask 90 silversmiths. formulations containing 107. 158 Simple Cream see Aqueous Cream BP specific weights. London Pharmacopoeia (8th edition) 11 Simple Linctus BPC 248 spectacles (safety glasses) 66 Simple Linctus Paediatric BPC 248 spicers 4 Simple Ointment BP 79. W. 168 swan-necked carboy 40 formulations containing 86. 54. English Glassware in the 17th Century 38 see also rectal absorption tiles surface area see body surface area for ointments 69.286 | Index emptying time 209 synthetic thickeners 86 pH 209 syringes 59. mould calibration 185 Zinc Ointment BP 173 . absorption 209 general principles 184 therapeutic incompatibilities 212 glycerol. formulations containing 158. 254. 167. 255 tared bottles 97 sulphurous acid 81 taring suppositories 183. balances 51 general principles 116 tolerance (pharmacological). paediatric 187 Therapeutic Substances Act (1925) 7 moulds 69.A. 209 tragacanth 86. 95 syrup bottles 40 powders 206 syrups 29. 105. 127. age range 208 external preparations 120 tolerance (error limits). storage 182 copper sulphate 186 terminal illness. 42 trituration 154 synthetic fats. opioids 207 packaging 128 topical absorption. 184 of containers for liquids 97 auxiliary labels 92 electronic balances 54 bases 80. 229 sulphur. 80 expiry dates 92 theophylline. 185 tartaric acid 84 codeine phosphate 186 tartrazine 89 Compound Bismuth Subgallate 191 temperatures. 89. 240 strength of medications 59 tablet bottles 96. 72 surfactants 87 pill-making 27 suspending agents 85. 262 temperatures 182 see also viscous liquids stramonium. suppository bases 80 sodium saccharin. infants 209 sustained-release preparations 116. 184. for Calamine and Coal Tar tablets Ointment BP 172 counting. 97 Strong Coal Tar Solution BP. as emulsifying agents 137 148 synthetic suppository bases. 138 sweet taste. Bentonite BP 86 displacement values 185 Theobroma Oil BP 19. 185. tolerance to opioids 207 definition 262 tetanus organisms. 116 tinctures 29. manual 72 succi 25 counting equipment 69 succi spissati 21 crushing for children 209 sucrose definition 262 as preservative 82 making emergency suspensions 117 solution (syrup) 89 Talc Dusting Powder BP 196. formulations containing 238.. 226. neonates 209 tragacanth 86 total body water. 250. 30 antioxidants 84 resinous 212 auxiliary labels and expiry dates 92 toddlers. flavourings to reduce 90 see also Compound Tragacanth Powder BP symbols. 124. for Liquid Paraffin Emulsion BP synthetic oils. 187 thickening agents 85 paediatric. 69 storage syrup (sucrose solution) 89 instructions on labels 91. glycerol 187 thiomersal 81 preparation methods 186 Thorpe. weights and measures 41. 73 Therapeutic Substances Act (1956) 7 calibration 69. 118 Tinaderm Powder 196 suspensions 115. 95 Wedgwood. 63. 64 Whitfield’s Ointment (Compound Benzoic Acid see also liquid(s). 164 underdosing 212 water-soluble bases 79 unit dose powders see individual unit dose powders waters 32 Unna’s Paste (Zinc Gelatin BPC) 167 waxes 87. 197 Venereal Diseases Act (1917) 7 safety procedures 66 ventilation. as emulsifying agents 137 vs volumes 41 vehicles 76 metric system 49 emulsions 133. 55. suspensions 117 weights (amounts) viscous liquids in percentage strength 61 bottles for 40 suppository moulds 69 measuring 59 weights (for balances) 52 mixing 104 Weights and Measures Act (1878) 36 see also syrups Weights and Measures Act (1970) 43 volatile ingredients Weights and Measures Act (1985) 51 aromatic oils as emulsifying agents. 170 vs weights 41 White’s Tar Paste 166. cachets 19 wines 34 warning labels 95. 88. 138. labels 95 syrups 54 videos see online material weight (body) vina 34 ideal 211 vinegars 32 paediatrics 210 viscosity. 114. 206 wool alcohols 79. Index | 287 troches see lozenges water baths 74. 137 ointments 53 see also bases powders 53. 137 water Wool Alcohols BP 87 for emulsions 137 wool fat 79. 167. bougies 19 weighing 35 valerian (Infusion of Valerian BPC) 23 capsules 201 varnish. 178. as absorption bases 164 water-miscible bases 79. 75 troy weights 35 Water for Injections BP 77 turmeric 88 water-in-oil creams 153 turpentine resin 28 water-in-oil emulsions. spatulas 158 Winchester quart bottle 40 wafers. classification amounts 135 of balances 51 incorporation in creams 155 welfare state 7 incorporation in ointments 165 wet gum method 135 inhalations 120 wet-seal cachets 19 volumes 56 wetting agents 86. work areas 66 skill 49 verbs. emulsions 135 white coats 66 creams 160 White Liniment BP 150 effect of adding solutes 61 White Liniment BPC 251 historical systems 41 White Soft Paraffin BP 78. Josiah (ceramic technologist) 38 urethra. 163 unofficial formulae 75. 94. pills 28 historical systems 41 vegetable oils. measuring Ointment BP) 253 vulcanite. 212 bulk oral powders 196 White Beeswax BP 78 calculations. 137 as solvent 76. 254 in percentage strength 61. calculation of Weights and Measures Regulations (1963). 77. infants 209 work areas 66 . 101 Wool Fat BP 87 total body. 229. 167. 173. 202. wrapping. 255 zinc oxide. 170 zinc sulphate. International zeroing see taring Pharmacopoeia 15 zinc. 260 .288 | Index World Health Organization. formulations containing 166. 255 Yellow Soft Paraffin BP 78. formulations containing 177. 254. 226. suppositories 69 213. 178. formulations containing 250.