Metformin Hydrochloride Sustained Release Tablets

Metformin hydrochloride ( MH ) is an oral antihyperglycaemic agent widely used in the management of non-insulin-dependent diabetes mellitus ( NTDDM or type-2 diabetes). It reduces blood glucose levels, predominantly by improving hepatic and peripheral tissues sensitivity to insulin without affecting the secretion of this hormone. It also appears to have potentially beneficial effects on serum lipid levels and fibrinolytic activity. Combining with other filers , a sustained release tablet (SRT) of once daily administration was prepared by using hydropropyl methylcellulose as basic matrix material.On the basis of pharmaceutical preformulation studies , the preparation technique and optimized formulation of MH SRT , which extend the drug release to 8 hours in vitro , were determined by single-factor test and orthogonal design test according to cumulative percent of drug release. The test of quality and the basic stability of three batches of tablets prepared by optimized formulation were carried out . The Higuchi model were used to study the releasing mechanism of MH sustained release tablets .Combing with matrix-sustained release technique ,the MH SRT ,which extend the drug release to 12 hours in vitro were studied respectively by using press coating technique, organic solvent coating technique and pseudolatex coating technique. The effecting factors of different coating techniques were studied basing on the unchanging of tablet formulation. Finally the latex coating technique were adopted . By changing the percentage of hydropropyl methylcellulose and Surelease(ethylcellulose pseudolatex) in coating solution with dibutyl sebacate as plastics , the release of MH were successfully controlled . By the time ,the sustained release mechanism of film coating were studied.The pharmacokinetics of MH SRT and commercial tablet in dogs were studied. The results showed that these two dosage forms were bioequivalent by single oral administration The IVIVC(in vitro-in vivo correlation) was also encouraging.