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 (900K and 4M) of Polyethylene oxide (PEO, 900K and 4M) in tablet core was studied. The release studies were done in phosphate buffer pH 6.8 using USP apparatus II and phosphate buffer pH 6.8 were used for the release studies, meanwhile a promising formula was tested in biorelevant media. Stability of some selected formulationse was carried-out for 6 months, at bench and accelerated conditions. Evaluation included: MH content, DSC, SEM, drug release and kinetics. Results revealed that increasing PEO percentage within the core drove to decreased MH release. SEM confirmedverified 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 upon 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 formulationse.
Key words: Controlled porosity osmotic pump, Metformin Hydrochloride, Biorelevant media, FaSSGF, FaSSIF, Stability studies.
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