| The paper discussed the manufacture of Sodium Valproate sustained-release tablet using Sodium Valproate microcapsule prepared by spray drying method. EUDRAGIT S was adopted in the study as bowel dissolving material, HPMC as matrix material. The VPA sustained-release tablet could keep releasing for twenty-four hours in vitro. The determination of its release in artificial bowel fluid was set up and methodological review was made. The paper discussed the factors which influence the release of VPA sustained-release tablet including viscosity of HPMC, quantity of HPMC, optimize the VPA sustained-release tablet prescription.The determination method of VPA content was set up for the very first time by reversed-phase ion-pair HPLC. The recoveries of VPA in low, medium, high density rate were 100.1%±0.64%,100.1%±0.50%,99.8%±0.52%。The release law of the VPA sustained-release tablet in vitro was studied initially. The accumulated release rate were matched by the zero class release model, single exponential model, Weibull model,Higuchi model and the Ritger-Peppas equation. The results showed that the Ritger-Peppas equation described the law better, and the releasing parameter equaling to 0.5176(0.45time data in dogs. After administrating single dosage of the VPA sustained-release tablet and the reference preparation to dogs respectively, Cmax were 34.51±7.36μg.ml-1and 63.33±11.95μg.ml-1,Tmax were 11.66±2.07h and 2.65±1.26h,T1/2 were16.22±3.79 h and 16.11±4.66 h,AUC0-t were 1243.26±302.80 and 1046±143.5μg.h.ml-1.MRT0-t were 23.02±1.87h and 16.65±3.2 h respectively.The relative bioavailability of VPA sustained-release tablets were 123.26±43.16(%) compared with the common tablets. Results from statistics showed that there were significant difference between the VPA sustained-release tablets and the common tablets in AUC0-t, Cmax and Tmax . The VPA sustained-release tablets and the common tablets were not bioequivalent. The concentration of VPA can be detected in blood serum within 48 hours. Comparing to the ordinary tablet, Cmax in VPA sustained-release tablets decrease, Tmax increases, and MRT prolongs. The results of the pharmacokinetics study in the dogs indicate that the VPA sustained-release tablet retention prolongs, the release decreases and the purpose of once daily designed by the research was achieved initially.In vivo-in vitro correlation of the VPA sustained-release tablet was evaluated by Wanger-Nelson method. The significant regression equation between the in vivo absorption and the in vitro release were got and in vivo-in vitro correlation was good. The release determination method created by the study was proved to be scientific and reasonable, which could guarantee the internal quality under the control. The paper discussed the common pathway of the development and manufacture of the sustained-release preparation through bowel dissolving sustained-release microcapsule prepared by spray drying method. The method is especially suitable to those drugs which produce stimulation in gastrointestinal tract and are prone to get wet; and the method provides an new technique for the preparation of drugs which can release on the different bowel segment controlled with PH. The study explored the formula optimization and the quality standard established by the instruction of the design and the screening of the susta... |
PDF Full Text Request