双嘧达莫缓释滴丸的制备及体内外研究

Preparation,in vivo and in vitro study of dipyridamole-loaded sustained-release dripping pills

目的:制备双嘧达莫缓释滴丸,使药物释放不受pH变化影响,提高生物利用度。方法:采用紫外分光光度法,考察不同pH条件下缓释滴丸释放特性。以硬度、释放度为主要考察因素,选取代表处方制备缓释滴丸,在此基础上以正交试验优化处方。采用单次给药双周期交叉方案,以市售双嘧达莫普通片为参照,进行兔体内药动学初步研究。结果:缓释滴丸的体内外药物释放达12h,且不受pH变化影响,相对生物利用度为(127.4±3.4)%,体外释放符合一级动力学方程。结论:采用联合载体技术制备的双嘧达莫缓释滴丸缓释性良好,药物释放不受pH变化影响,兔体内药动学研究表明生物利用度优于市售普通制剂。

Aim：To prepare sustained-release dipyridamole （DIP） pills with the expected features of pH-independent drug release in vitro behavior and increased bioavailability. Methods： Accumulative drug release from the pills prepared by the solid dispersion was determined using UV spectrophotometer and the effect of pH value of the medium the on the release was investigated. The orthogonal design was used to select the optimal formulation based on the hardness and percent release. The preliminary evaluation of relative bioavailability in the animal models was carried out by single-dose crossover design. Results：Drug release from the dripping pills was found to be pH-independent and sustain for 12 h both in vivo and in vitro. The relative bioavailability was （127.4 ± 3.4）%, and the release was best fitted into first-order kinetics. Conclusion：The release behavior of the prepared DIP pills shows evident sustained-release characteristics, and it is pH-independent. Animal study indicates that the bioavailability of the DIP pills is higher than that of commercial immediate-release DIP tablets.