Physicochemical propertiesSolubility Stability Hydrophilicity LogP pKa Physical state Melting point UV max Storage Other information Freely soluble in water slightly soluble in alcohol practically insoluble in acetone and in dichloromethane. Protect from light and moisture. Hydrophilic -o.5 12.4 Solid 223-226°C 233 nm in water. Store between 15-30° C (59-86° F). Dispense in light resistant container. Hygroscopic nature decreasing intestinal absorption of glucose.Pharmacological Properties 1 2 3 4 Use/Category Bioavailability (%) Protein Binding (%) Main elimination route Antidiabetic.03 (500 mg) 1. Metformin's mechanisms of action differ from other classes of oral antihyperglycemic agents. These effects are mediated by the initial activation by metformin of 5 6 7 Elimination half-life (h) Duration of action (h) Cmax(µgml-1) 8 Tmax(h) 9 T1/2(h) 10 Bioavalability (F) 11 First pass metabolism 12 Mechanism of action . and improving insulin sensitivity by increasing peripheral glucose uptake and utilization.60 (850 mg) 3 hours 6 hours Absolute bioavaibility F= 0.used to treat type-II diabetes Used in treatment of Polycystic ovary syndrome 50-60 % Metformin is negligibly bound to plasma proteins. 8-12 hours 1. Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion.5 times that of creatinine clearance.5-0. Metformin decreases blood glucose levels by decreasing hepatic glucose production.6 No hepatic metabolism. 2-6 hours. indicating the tubular secretion is the primary mode of metformin elimination. Approximately 90% of the drug is eliminated in 24 hours in those with healthy renal function Renal clearance of metformin is approximately 3. a liver enzyme that plays an important role in insulin signaling. resulting in insulin-independent glucose uptake. The rare side effect. However. and vomiting followed by diarrhea drowsiness weakness dizziness malaise and headache might be seen. Increased peripheral utilization of glucose may be due to improved insulin binding to insulin receptors. AMPK is known to cause GLUT4 deployment to the plasma membrane. whole body energy balance. lactic acidosis. Activation of AMPK is required for metformin's inhibitory effect on the production of glucose by liver cells.13 Side effects AMP-activated protein kinase (AMPK). those with severe renal impairment may accumulate clinically significant serum lactic acid levels. is thought to be caused by decreased liver uptake of serum lactate. Other conditions that may precipitate lactic acidosis include severe hepatic disease and acute/decompensated heart failure. and the metabolism of glucose and fats. Metformin administration also increases AMPK activity in skeletal muscle. epigastric discomfort nausea. In those with healthy renal function. one of the substrates of gluconeogenesis. the slight excess is simply cleared. . Work done on drug Sr. HPMC K15M and carbopol 940 Polyethelyne oxide(PEO) HPMC K4M and K100M To develop oro-dispersible tablets of metformin by direct compression method using super disintegrant approach. To formulate sustained release matrix tablet and mask bitter taste of drug. To obtain sustained release by swelling and erosion of polymer. gum copal and gum damar Cation exchange resin. effervescent approach and sublimation approach To develop an oral sustained-release (SR) metformin tablet prepared by the direct compression method. . using hydrophilichydroxylpropylmethylcellulos e(HPMC) and Guar gum polymer alone and in combination at different concentrations.indion 264 and HPMC K100M To formulate sustained release matrix tablet. To formulate sustained release matrix tablet. 1 Orodispersible tablet Polymers used Justification 2 Sustained release matrix tablet HPMC and guar gum. 3 Floating dosage form 4 5 6 Highly porous gastroretentive tablet Response surface optimization of sustained release metforminhydrochloride matrix tablets Sustained release tablet Psyllium. 7 Sustained release taste masked tablet Eudragit RSPO. To formulate anti diabetic drug Metformin as a controlled release floating delivery making use of Psyllium as release retardant. Dosage form no developed . indion 244. 11 12 13 14 15 16 17 polyvinylpyrro lidone (PVP) tamarind seed gum (TSG) and HPMC. To formulate sustained release Gastroretentive tablet. To formulate sustained release mucoadhesive pellets.NaCM pellets C. To formulate sustained release microsphere. To formulate sustained release floating tablet. Sustained release Triacylbetacyc tablet lodextrin andHPMC. acid and sodium bicarbonate PEO and To formulate sustained release matrix eudragit L100 tablet. Gastroretentive NaCMC. and Precirol.Na tablet alginate and Eudragit NE 30 Mucoadhesive HPMC. xanthan gum. Eudragit L100-55. To formulate sustained release niosome.8 Effervescent floating tablet 9 pH controlled delievery(matrix tablet) 10 Floating tablet HPMC. chitosan. ethylcellulose . To formulate floating microspheres in order to increase its residence time at 18 Floating microshere . stearic To develop effervescent floating tablet.Carbopol and Na alginate Mucoadhesive HPMC and pellets MCC Non-ionic surfactant vesicles(Niosome) Nano particle Eudragit RSPO/PLGA Microsphere Pectin - To formulate sustained release matrix tablet. To formulate sustained release mucoadhesive pellets. To formulate sustained release nanoparticle. the site of absorption and thus improve its bioavailability. and to extend the duration of action along with possibilities of dose reduction. . It may be gradually increased if needed. given with or after a meal. or 500 mg twice daily. As given in adult Pediatrics Geriatrics . at intervals of at least 1 week.Dose of drug Adult Initial dosage is 500 mg two or three times daily or 850 mg once or twice daily with or after meals. to 2 to 3 g daily For 10 years old children starting dose of 500 mg or 850 mg once daily. gradually increased if necessary. to a maximum of 2 g daily given in 2 or 3 divided doses. at intervals of at least 1 week. Marketed product SNo Brand Name 1 Bigesens (500mg) 2 Bigesens XR(500mg) 3 Bigesens XR (1 gm) Exermet (500mg) Formin(500mg) Manufacturers Zydus Cadila Healthcare Ltd CND (Zydus Cadila Healthcare Ltd) Zydus Medica (Zydus Cadila Healthcare Ltd) Cipla Limited Dosage form Tablet Tablet(extended release) Tablet(extended release) 4 5 6 7 8 Tablet Tablet Tablet Tablet Tablet 9 10 11 12 13 14 15 16 Alkem Laboratories Ltd Formin (500 mg) Stadmed Pvt Ltd Formin (850 mg) Alkem Laboratories Ltd Forminal(500mg) Alembic Chemical Works Co Ltd Forminal (850 Alembic mg) Chemical Works Co Ltd Forminal SR Alembic (500mg) Chemical Works Co Ltd Gluformin(500 Abbott mg) Healthcare Pvt Ltd (AHPL) Glumet Cipla Limited Glumet (850mg) Cipla Limited Glumet EXT Cipla Limited Glumet -XR Protec (Cipla Ltd) Insumet Cadila Pharmaceuticals Tablet Tablet(sustained release) Tablet Tablet Tablet Tablet(extended release) Tablet(extended release) Tablet . 4.S. Cadila Pharmaceuticals Ltd. http://www.ca/drugs/DB00331 2.ncbi.V.nih.gov/pubmed 5. Lincoln Pharmaceuticals Ltd Lincoln Pharmaceuticals Ltd Ranbaxy Laboratories Ltd. Ltd. Laboratories (India) Pvt. A.17 Insumet (850 mg) Insumet SR 18 19 Irmet 20 K -Met SR 21 K -Met SR (1000 mg) M -Forlin 22 23 M -Forlin (850 mg) Riomet 24 Ltd. Blue Cross Laboratories Ltd. http://www. 36th edition.Pharmaceutical Press.drugbank.nlm.drugs. page no 453. Cadila Pharmaceuticals Ltd.com/ .html 3.com/international/metformin. Blue Cross Laboratories Ltd. Martindale. Tablet Tablet(sustained release) Tablet Tablet(sustained release) Tablet(sustained release) Tablet Tablet Oral Solution Reference :1. http://www. http://www. The complete drug reference.sciencedirect.