To study the efficacy of co-crystallization technique in enhancing the bioavailability of oral hypoglycemic agents

Abstract

The bioavailability of the drug is mainly governed by factors like partition coefficient, solubility Pka, etc. The modification of these physicochemical properties can be done to enhance the bioavailability and thus effective therapy can be achieved. This research deals with the advantages of co-crystals over salts, solvates (hydrates), solid dispersions and polymorphs. A pharmaceutical co-crystal is a single crystalline solid that incorporates two neutral molecules, one being an active pharmaceutical ingredient (API) and the other a co-crystal former. In the present study co-crystals of Metformin Hydrochloride and Glimepiride were prepared using different co-formers. Different ratio of urea, succinic acid and tartaric acid were used to design the co-crystals. They were formulated by two different methods- cooling crystallization and solvent evaporation. The prepared co-crystals were evaluated for microscopic characters, product yield, Fourier Transform Infrared Spectroscopy, Micromeretic properties, drug content, dissolution study of co-crystals, stability studies. The results indicated that co-crystals prepared by using a suitable co-former can definitely enhance the dissolution rate ultimately leading to enhanced bioavailability. Out of three co-formers used to design the co-crystals, succinic acid is found to be more effective. Moreover the bioavailability of Glimepiride is more enhanced as compared to Metformin Hydrochloride as it belongs to BCS class II.