Metformin hydrochloride and Gliclazide are oral hypoglycemic agents 1) belonging to biguanide group and secondgeneration sulphonyl urea respectively. Generally, they are individually used in the treatment of type II non-insulin dependent diabetes mellitus. The combination of both the drugs are also available and it is reported 2) to be effective than individual therapy. Metformin acts 3) by decreasing hepatic glucose production and improves insulin sensitivity by increasing peripheral glucose uptake. Because of its shorter and variable biological half-life 4,5) of 1.5-4.5 h, it should be repeatedly administered (500 mg thrice a day) to maintain effective plasma concentration. Gliclazide reduces 6) the glucose level by direct stimulation of insulin release from beta cells of pancreatic islet. Relatively Gliclazide is having longer biological half-life (6-15 h) depending upon individual and the dose 7) is 80 mg two-three times a day with meals. Combination of Metformin-500 mg and Gliclazide-80 mg per tablet is available in India and it is to be taken two to three times a day to get required effect.In the present study, we attempted to formulate Metformin/Gliclazide extended release tablet by using Eudragit NE30D aqueous dispersion, with an intention to extend the drug release over a period of 8-12 h, hence it can be taken once a day. The formulated tablets were analysed for drug content by a validated HPLC technique developed in our laboratory and characterized by various physicochemical parameters such as disintegration time, hardness, friability, thickness, weight variation and in vitro drug release.
Materials and MethodsMaterials Metformin hydrochloride and Gliclazide (gift samples from Mederich Sterilab Pvt Ltd., Bangalore, India), Eudragit NE30D (Rohm Pharma, GmbH, German), Colloidal anhydrous silica (Pioma Chemical Ltd., India), dibasic calcium phosphate (Citorgia Biochemicals Ltd., Vishakhapatnam, India), polyvinylpyrrolidone (PVP K30, ISP, International Corporation, Mumbai). All reagents used were of either HPLC or analytical grade.Formulation of Tablets The extended release tablets were formulated by using wet granulation technique. The Metformin hydrochloride was passed through sieve #100. Gliclazide, dibasic calcium phosphate, colloidal anhydrous silica and PVP K30 were passed separately through sieve #40.Then the required amount of powders as given in Table 1 were mixed in a 10 l capacity rapid mixer-granulator (Rotamix HSMG-10, Kevin Engineers, India) for 5 min. Then the required quantity of Eudragit NE30D was added in divided portions to the mixed powder and the granulation was done in rapid mixer granulator for 3 min. Eudragit NE30D was as a binder and as well as polymer to extend the drug release. The granules obtained were kept at 40°C for 30 min in a tray drier (Bombay Engineering Works, India). At semi dried condition the granules were passed through sieve #14 and then dried at 40°C until loss on drying becomes 2.5% in IR balance (Advanced Ltd., Mumbai, India). Finally, the granules were lubrica...
