Formulation and stability studies of metformin hydrochloride in a controlled porosity osmotic pump system

Abstract

This study was designed to formulate, for the first time, metformin hydrochloride (MH, 850 mg/tablet) as a controlled porosity osmotic pump (CPOP) system to achieve zero-order release pattern. MH core tablet was coated with cellulose acetate membrane containing PEG 400. The effect of different percentages and molecular weights of polyethylene oxide (PEO, 900K and 4M) in tablet core was studied. The United States Pharmacopeia (USP) apparatus II and phosphate buffer pH 6.8 were used for the release studies; meanwhile, a promising formula was tested in biorelevant media. The stability of some selected formulations was carried out for 6 months, at bench and accelerated conditions. Evaluation included: MH content, Differential scanning calorimetry (DSC), Scanning electron microscopy (SEM), drug release, and kinetics. Results revealed that increasing PEO percentage within the core decreased MH release. SEM verified formation of pores in the membrane that accounts for MH release. Almost all stored tablets were stable for all studied parameters. MH endothermic peak maintained its position and energy of enthalpy on storage as confirmed by DSC. MH release rate from a promising formula, following zero-order release model, increased by 28% in biorelevant media compared to phosphate buffer. Subsequently, in vitro release in biorelevant media could be employed as a tool to anticipate in vivo tone of CPOP formulations.