CAPSULES Definition Capsules are solid dosage form in which the drug substance is enclosed in water soluble shell or envelope. Capsule gelatin. shell is mostly made up of US Pharmacopeia (USP 24): It defines capsules as solid dosage forms in which the active ingredients are sealed in a hard or soft container or shell. The European Pharmacopoeia (Eur. Ph.) describes capsules as follows: 'Capsules are solid preparations with hard or soft shells of various shapes and capacities, usually containing a single dose of active ingredient. They are intended for oral administration.' History The capsule is one of the oldest dosage forms in pharmaceutical history, known to the ancient Egyptians. The earliest European reference is contained in a travel account of 1730 which mentions the pharmacist de Pauli from Vienna, who produced oval-shaped capsules in the hope of covering up the unpleasant taste of the pure turpentine he prescribed for people suffering from gout. A further 100 years were to pass before the first gelatin capsule appeared. The first patent for such a product was granted in 1834 to the pharmacist Joseph Gérard Auguste Dublanc and the pharmacy student François Achille Barnabé Mothès. Mothès, who ended his collaboration with Dublanc in 1837, continued to work on improving the gelatin capsule and to take out patents for the manufacture and use of capsules. was granted a patent for his 'medicine coverings'. Eventually. capsules were being produced in many different parts of the world. in 1846. The Frenchman Jules César Lehuby was successful in this strategy and. Mothès' invention was so successful that. . not least to circumvent those held by Mothès. which formed the basis of his future inventions. this resulted in several more patents for gelatin capsules being taken out by others. by the following year. It was in 1931 that Arthur Colton.. which he produced by dipping silver-coated metal pins into a gelatin solution and then drying them. Davis & Co. He was also the first to suggest two-piece capsules. on behalf of Parke. succeeded in designing a machine which simultaneously manufactured both bodies and caps and fitted them together to form a hard gelatin capsule . Prevention of drug by gastric pH or enzymes. Drugs which cannot be compressed can be given in capsule form. Economical. Increased bioavailability.made from gelatin. easy to handle and carry and attractive in appearance. Therapeutically inert . .Advantages Drugs with unpleasant taste and odour can be administered. Oily medicaments can be administered. . Efflorescent (softens the capsule) and hygroscopic drugs (absorbs water and makes capsule shell brittle) cannot be filled. Not suitable for extremely soluble materials – sudden release may cause stomach irritation.Disadvantages Concentrated preparation which needs previous dilution may lead to irritation. Soft Gelatin capsule (one piece).Types of capsule Hard Gelatin capsule (two piece). . Common sources of collagen – animal skin.Heterogeneous product derived by irreversible hydrolytic extraction of treated animal collagen. sinews and/or bovine bones. . Gelatin .Gelatin Capsules – primarily manufactured by gelatin. Other materials – HPMC and starch.Raw Materials . do not pose the risk of BSE Can readily converted from sol (mobile liquid) to gel form (rigid).Gelatin Exhibits excellent physicochemical and biological properties. Marinecaps .fish gelatin. . Gelatin from bovine source – Transmission of bovine spongiform encephalopathy (BSE) Used from countries where low incidences of BSE is there.Raw Materials . Fish gelatin made from non-ruminant material . Alkali treated Pig Skin. HCl. Extraction through hot water. Evaporation of water – dried gelatin. Evaporation of water – dried gelatin. HSO3 or H3PO4 Calcium Hydroxide. Isoelectric point – between 4. Immersed for1-3 months. Extraction through hot water. Solution cool to form gel.7 to 5. H2SO4.3 . Immersed for 1 day. Demineralised bones. Isoelectric point – between 7 to 9. Solution cool to form gel.Gelatin Manufacturing Type A Type B Acid treated. . . Pork skin Gelatin • Plasticity and clarity. • Normally used for hard capsule production. • Tends to be hazy and brittle. • Reducing haze or cloudiness. Blend of bone & pork skin Gelatin • High gel strength.Bone Gelatin • Tough and firm film. . • Range: 30-60 millipoise. • Soft Gelatin – 150-200.Physicochemical Properties of Gelatin Bloom Strength • Measure of gel rigidity.7mm) to a defined depth (4mm) within an aged gelatin solution (6. • Measured on standard 6.66% w/w solution at 60°C in a capillary. • Weight (in grams) required to depress a plunger (of defined diameter. Viscosity • Controls thickness of film or sheets. • Hard Gelatin – 250-280. 12.66% w/w in water). Soluble in biological fluids at room temp. Excellent mechanical properties exhibiting good film and hence capsule forming properties. (Note: Gelatin Capsules do not dissolve but swell when immersed in an aqueous solution <30°C. . Excellent rheological properties at elevated temp.] Undergoes sol-gel transition at relatively low temp. [Sol (mobile liquid) at 50°C – good for dip processing. Other Raw Materials Diluents Binders Disintegrants Lubricants Plasticizers Colorants Wetting Agents Preservatives . Walls of hard gelatin capsule are firm and rigid. sucrose and acacia(optional) . sorbitol.To prevent brittleness plasticsers are added. Whereas walls of soft gelatin capsule are more soft and flexible. Eg: Glycerol. propylene glycol. So soft gelatin contains large proportion of plasticiser. 65:1 Capsules containing oil with added surfactant or products with hydrophilic liquid fills. 0.46:1 Oral capsules with oil films where shell requires to be more elastic. 0.35:1 Oral capsules with oil films where final capsule should be hard.55-0. 0. .Glycerol/Gelatin Ratio Application 0.76:1 Oral capsule where a chewable shell is required. lavender .hallucinogenic effects. orange or yellow .Important role in identifying the product Improve the patient compliance.analgesia. .stimulants and antidepressants. May be included in heated gelatin. Two types – soluble synthetic (coal tar) and insoluble pigments (titanium dioxide & iron oxides) Titanium dioxide – white opacifying agent & provides protection against light or to conceal the contents. White . FDC approved colours or approved by legislation of that particular country. 15% w/w) Increase the wetting properties of capsule shell.(< 0.Sodium Lauryl Sulphate. Enhance the wetting of gelatin solution on metal pins during manufacturing process. May be included in heated gelatin. In turn enhance the dissolution properties of formulation. . Sometimes added to prevent microbial contamination. Usually parabens are used. . Usually antibacterial agents are used but soft gelatin capsules contain antifungal agents also. Manufacturing of Hard Capsule Shells – Dip-Coating Method . Collection of gelatin from animal source Mixing with hot water Transfer to ss feed tanks Add excipients Stripping Drying Rotation Dipping Trimming Joining Sorting Printing . . the gelatin solution is transferred to stainless steel feed tanks.1. After aging in stainless steel receiving tanks. Once raw materials have been received and released by Quality Control. the gelatin and hot demineralized water are mixed under vacuum in Stainless Steel Gelatin Melting System. . 2. and any needed water are added to the gelatin in the feed tanks to complete the gelatin preparation procedure. .3. opacifants.Dyes. The feed tanks are then used to gravity-feed gelatin into the Capsule Machine. 4. the gelatin is gravity fed to Dipper section. whereas the dipping solution is maintained at a temperature of about 500C in a heated. jacketed dipping pan. The length of time to cast the film has been reported to be about 12 sec. Dipping From the feed tank. . Pairs of the stainless steel pins are dipped into the dipping solution to simultaneously form the caps and bodies. The pins are at ambient temperature. pins are elevated and rotated 2-3 times until they are facing upward. This rotation helps to distribute the gelatin over the pins uniformly and to avoid the formation of a bead at the capsule ends.5. Rotation After dipping. Pin Bars rise to the upper deck allowing the cap and body to . 6. Drying The Pin Bars pass through the upper and lower kilns of Capsule Machine Drying System. and humidity. temperature. . removes the exact amount of moisture from the capsule halves. Here gently moving air which is precisely controlled for volume. . Stripping Once drying is complete. A series of bronze jaws strip the cap and body portions of the capsules from the pins.7. the Pin Bars enter the Table section which positions the capsule halves for stripping from the Pins in the Automatic section. Trimming The stripped cap and body portions are delivered to collects in which they are firmly held. As the collects rotate.15 mm tolerance. The cap and body lengths are precisely trimmed to a ±0. .8. knives are brought against the shells to trim them to the required length. . Finished capsules are pushed onto a conveyer belt which carries them out to a container. Joining (Sealing) The cap and body portions are aligned concentrically in channels and the two portions are slowly pushed together.9. SEALING Sealing Mechanical sealing Gelatin Band sealing Hydroalcoholic solvent seal . . Positive interlock is created between the cap and body portions.Mechanical Sealing (KAPSEAL Technology) Self locking is made by forming indentations or grooves on the inside portion of the cap and body portions. Eg: Coni Snap. Indentations formed further down of the cap provide a pre-lock that keeps the empty capsules joined during shipping and handling Yet allows ready separation for filling. . Gelatin Band Sealing Dilute solution of the gelatin is applied to the centre of the capsule (between the two halves) which. once dried. produces a hermatic seal . Robust & impervious . Setting & hardening – overnight at room temp. This softens the capsule and following heating to 45° C the interface fuses to produce a seal. Larger size of seal area as compared to banding process.Hydro alcoholic Solvent Seal A hydro alcoholic solution (1:1 water/ethanol) is applied to the centre of the capsules (between the two halves). single wall thickness. Temperature at drying. 3. Gelatin viscosity. and colour. Processing parameters throughout the production process. Humidity 2. . 4.The entire cycle lasts approximately for 45 minutes. moisture content. Capsule quality is monitored throughout the production process including size. Speed of rotation. : 1. 10. the capsules passing on a lighted moving conveyor are examined visually by inspectors. . Sorting During sorting. Defects are generally classified according to their nature and potential to cause problems in use. 11. Printing In general. capsules are printed before filling. If there is any damage to capsule during printing no active ingredients would be involved. Empty capsules capsules can be handled faster than filled capsules. Print either axially along the length of capsules or radially along the circumference. . Offset rotary presses having throughput capabilities as high as three-quarter million capsules per hour. It helps retain brand identity right until it reaches the customer. Brandshield . twocolor printing of the capsule.Circular oriented. Allows you to print two unique colors on the cap and on two colors on the body of the capsules. brand name and graphics right on the capsule. . This printing technique allows you to differentiate your brand and is an effective anti-counterfeit measure.Brandshield 4c Capsules Hard capsules that feature fourcolor circular oriented printing. providing exceptional brand awareness. Imprint your brand logo. These capsules offer counterfeit security right up to the end user. 13 SRTM University. NandedDept.45 08 June 2009 SIZE & SHAPE: Empty gelatin capsules are manufactured in eight sizes.296 3 0.760 0 0.168 0.104 .544 1 0.30 0.400 2 0.21 5 0.95 0.096 00 0.37 1. of Pharmaceutics 0.50 0. Tapped Bulk Density X Capsule Volume = Capsule Fill Weight Size Volume (cm3) Fill weight(g) at 0. ranging from 000 to 5.37 0.8 g/cm3 powder density 000 1.68 0.240 4 0. . respectively. Lilly’s pulvule tapers to a bluntly pointed end. The standard shape of capsules is traditional symmetrical Oblong shaped. e.5 g. 11.g. Smith Kline Beacham’s spansule capsules taper at both the cap and body ends. . and 12 having capacities of about 30. and 7. Some manufactures have employed distinctive shapes. Three larger size are available for veterinary use: 10. The largest size normally acceptable to patient is a No: 0. 15. Eg: Dried silica. Maintain relative humidity of 40-60% Desicant materials are used. More than 16% . Best to avoid extremes of temperatures.STORAGE Equilibrium moisture content – 13-16% Critical to maintain the physical properties of the shell.Soft & Sticky Less than 13% Brittle and Fragile . clay and activated carbon. . cultural or religious restrictions. citing the environment and/or animal welfare.Vegetarian Capsule – Need Animal-free products . breast cancer. as well as driven by health concerns such as heart disease. high cholesterol and weight control they are moved by ethical considerations. These consumers are concerned with general good health and well-being.driven by personal. or simply a preference not to consume animal based products.