Nicorandil Sustained Release Tablets Preparation And In Vivo And In Vitro Release Study

Objective: The study aims to develope Nicorandil sustained release tablets by methods of modern science and technology.This thesis studys preparation and pharmaceutical formulations of Nicorandil sustained release tablets; examines in vitro release mechanism and characteristics of sustained release tablets; studys Pharmacokinetics in rabbit,and evaluates the drug release process in the body. This topic founds a new forms of research and development for Nicorandil. It provides a safe,efficient,stable and controllable quality of the new formulation on Nicorandil sustained release tablets for cardiovascular and cerebrovascular diseases.Methods:1、Study on Preparation prescription and production processTargeting for the cumulative release percentage of Nicorandil,establishes the method and standard to determine release in vitro and studys pharmaceutical formulations and production processes.On the basis of HPMC amount and viscosity, the amount of EC、MCC and lactose in the univariate study. Uses Design-Response surface methodology to optimize the test results,and formulates the best preparation prescription finally.2、Determinnation and in vitro drug release properties of Nicorandil sustained release tabletsEstablish the methods of HPLC to determine the contents of Nicorandil sustained release tablets. Fitting in vitro release curves of sustained release formulation and studying its release mechanism,and these curves are zero-order release model、first-order release model、Higuchi equation and Rigter-Peppas model.Prepares "in vitro release volume- pH- time" three-dimensional release characteristics chart, then studys in vivo drug release properties.3、Study on PharmacokineticsEstablishing HPLC method to determine plasma drug concentrations of Nicorandil.By using Nicorandil general tablets as reference preparation,we determinate plasma concentrations and fit pharmacokinetic parameters of Nicorandil sustained release tablets in rabbits,evaluate release process of the drug in rabbits.Results:1、Through single factor and design-response surface method,preparation prescription and processin were finally determined. Preparation prescription was: 37.5% HPMC,22.5% EC,20% MCC and 15% Lactose. Production process was : tablet is weighing about 400 mg to prepare by direct compression methods.2、Established the determination of Nicorandil sustained release tablets,and the method was accurate, simple and reliable. Fitted four kinds of models of Nicorandil in vitro release curve release,and applications which used Higuichi equation and Ritger-Peppas equation were fitting better(r2 > 0.98),which pointing Nicorandil sustained release tablets was characterized by a synergistic effect of diffusion and erosion. Through the study of "release-pH- time" three-dimensional release characteristics, founding that changes of pH did not interfere with accessories release.So it is in line with demand design of the dosage form.3、The Pharmacokinetic studies showed Nicorandil sustained release tablets were fitted to single-department model in rabbits. Absorption rate constant of sustained release tablets(ka=1.3540h-1) was significantly less than conventional tablets(ka=3.5221h-1),which descripting it can delay drug absorption. Sustained release tablets plasma concentration-time area under the curve(AUC) were higher than the conventional tablet,which explaining the higher bioavailability of sustained release tablets. The statistical moment theory(non-compartment model) fitting study also showed that the average residence time of sustained release tablets(MRT = 3.5876h) extending approximately 2h by comparing with conventional tablets(MRT = 1.4119h),which descripting the better sustained release.Conclusions:The subject adopted design-response surface method to optimize pharmaceutical formulations,and identified the formulation and preparation of formulations. The subject established HPLC method for determination of Nicorandil release tablets, and developed the determination standard of sustained release tablets in vitro release. The prepared sample of sustained release tablets were in line with quality standards. The subject also studied in vitro release characteristics of Nicorandil sustained release tablets, and evaluated in vitro release and release mechanism of the drug. The subject studied Pharmacokinetics in rabbits of Nicorandil sustained release tablets,then avaluated and investigated the dynamic changes and in vivo release performance of the drug and its formulation in animals. The study provided an experimental basis and foundation for new formulations of Nicorandil development work.