Formulation Development and Evaluation of Modified Release Tablet Using a Fixed Dose Combination of Antidiabetic Agents

摘要

The present invention relates to formulate the bilayer tablet of antidiabetic agents comprising Vildagliptin (VLD) immediate release layer and Metformin Hydrochloride (MET) sustained release layer. VLD makes pancreas to produce insulin which helps to improve the glycaemic control in body and MET makes a better use of insulin in body. Both drugs does not alter pharmacokinetics of one another and hence attempt was made to formulate bilayer tablet of these two drugs to improve patient compliance, bioavailability, reduce dosing frequency and reduce GI side effect of MET. VLD (50mg) layer contained Cross Povidone as a super disintegrant and MET (500mg) layer composed different hydrophilic controlled release polymers like, HPMC K100M CR, Carbopol 934P and PVP K30 as a binder. The tablets were evaluated for all physicochemical properties. In-vitro drug release studies were performed as per USP in phosphate buffer pH 1.2 and phosphate buffer pH 6.8, using USP type I apparatus (Basket type). Based on in vitro drug release data for formulations A5 and F8 were selected as the optimized formulations. VLD immediate release layer (F4) contained 2.25% Cross povidone and MET sustained release layer (F8) contained combination of polymers, HPMC K100M CR and Carbopol 934P 15% and 7.5% respectively. The result obtained for formulation A5F8 showed that VLD was released 98.90% in 30 minutes and MET was released 98.92% for 12 hours satisfactorily. Optimized formulation observed to follow Higuchi model when different kinetic models were applied. The stability studies revealed no significant changes in physical and chemical properties of optimized formulation.