Study On Drug M Sustained-Release Tablets

Drug M is a diuretic agent to treat hypertension and dropsy.In this paper, drug M was selected as the model drug to prepare hydrophilic matrix tablets.And the drug release character and mechanism were studied.At last, the human pharmacokinetic study of drug M hydrophilic matrix tablets was performed,it was bioequivalent to imported tablets.The physicalchemical properties of drug M were investigated.Firstly the solubility of drug M in DMF ,THF, alcohol, methanol ,water and PBS pH1.0,pH2.0,pH4.0,pH5.8,pH6.8,pH7.4,pH7.8 were studied.Temperature, moisture had little effect on the chemical stability of solid drug M.Light made the related substance of drug M incresae.The main excipients were selected by studying the interaction of drug M and excipients through the influence factors methods and the DSC.In the formulation study of hydrophilic matrix tablets,the effects of many factors including formulation and technique on the release behavior of tablets were investigated. Based on the comprehensive singl-factor experiments,the sustained-release tablets were prepared with HPMC 4000cps and HPMC 5cps. The formulation were optimized by orthogonal design, having the accumulative release amount of 2hr, 4hr and 7hr as the evaluation target.The release behavior of tablets followed Ritger-Peppas kinetics (Y=0.7363X+3.0663, r=0.9995). At last the study advanced the mechanism of the drug release, that the drug was released by diffusion and corrosion mechanism according Ritger-Peppas equation (n=0.736).The release characteristics and content measurement method and related substance measurement method were elementally determined ,criterion of drug M sustained release tablets'quality control also was investigated.Based on above results the stability of drug M sustained release tablets were investigated.The study showed that the drug release characteristics,appearance, related substance and the content of well packaged preparation did not change after stored under 40℃and RH75% environment for three months.Comparing with the imported tablets, the the human pharmacokinetic study of drug M hydrophilic matrix tablets was performed. Cmax and tmax of imported tablets were 42.2ng/ml and 3.3hr, Cmax and tmax of drug M sustained released tablets were 36.5ng/ml and 4.3hr.The relative bioavailability was 101.9%.There wasn't significant difference between the two formulations. Obvious correlation was observed between absorption percentage in vivo and relesse rate in vitro.