Study On Preparation And Quality Of Sustaineded-release Tablets Of Metformin Hydrochloride

Metformin hydrochloride (MH) can be used in the treatment of type2diabetes. Either pharmacologically or chemically, MH is different from any other classes of oral antihyperglycemic drugs.For a single500mg dose of MH taken under fasting conditions,the absolute bioavailability is approximately50%to60%. Within the first24hours after oral administration, approximately90%of the absorbed drug is excreted in the urine. While in blood, the elimination half-life is approximately17.6hours,the plasma elimination half-life is approximately6.2hours. Because of the low bioavailability and short half-life of MH, the development of sustained-release MH forms is necessary.Osmotic pump preparation is able to delivery drugs in a sustained manner,independent of the drug properties.The treatment tolerability and patient compliance could be improved with prescribed dosing regiments.Osmotic pump preparation is composed of three parts, a tablet core, semipermeable membrane and an orifice drilled on the film.The semipermeable membrane can be generated by using film-coating spray equipment mainly with cellulose-based solutions,e.g.cellulose ace-tate or ethylcellulose,of organic solvents such as an acetone-water mixture.The high amount of solvent required could become problematic and costly. It’s not an environmental-friendly option.Various drilling techniques using manual-drilling or laser-drilling were developed.The complex drilling technology is a uneconomic choice. Consequently, the preparation of Osmotic pump is hard to be industrialized. In this paper, controlled-porosity osmotic pump (CPOP) of MH was prepared with polyvinyl acetate dispersion,Kollicoat SR30D,which has demonstrated to be a stable aqueous dispersion with good handling properties for coating and a strong sustained release activity.The flexibility of the polyvinyl acetate can be strongly increased by a small amount of plasticizer.Firstly, a controlled release mechanism hypothesis was generated to design the original model. Then, designing the new CPOP tablet and investigating the effect of different variables of coat formulations on drug release behavior by single parameter optimization.Results show that, the release is mainly affected by four factors,(i) the HPMC proportion in the membrane,(ii) the film thickness,(iii) the releses modifier agent (iv) the plasticizer grade and proportion.The tablets were tested for release behavior using different dissolution medium and stirring speed. The drug release is independent of the dissolution medium’s pH.The relese behavior could be influenced by the stirring speed and the osmotic pressure of medium. Results indicated that the relese mechanism of the CPOP tablets include diffusion and osmosis.In this study we report the successful formulation of MH-CPOP tablets, which were similar to the marketed product Foramet and able to satisfy the expected criterion limits and to deliver about90%of MH at a rate of approximately zero order for up to12h.The optimized CPOP tablets were stored under various temperature and humidity conditions.The stability were studied as per Chinese pharmacopoeia guidelines.The experimental results above showed that the polyvinyl acetate aqueous dispersion of Kollicoat SR30D could be adopted in the preparation of osmotic pump preparation of MH. Because of the obvious convenient and effective cost,this technology will be a new option of the Osmotic pump preparation.