[关键词]
[摘要]
目的 研究不同缓释辅料制备的喘平方缓释片在体外溶出过程中颗粒的脱落及其载药、释放情况,进一步阐明中药复方缓释制剂多指标成分的均衡释放机制。方法 选取喘平方(麻黄、洋金花等)为代表方,分别选用改良桃胶、HPMC为缓释辅料制备喘平方缓释片,通过体外溶出实验,于不同时间点,采用水下摄像法拍摄外部形态变化,同时用激光粒度仪测定脱落颗粒的粒径大小、HPLC法测定多指标成分(麻黄碱、伪麻黄碱、东莨菪碱)的释放度,计算累积释放曲线斜率(K值)评价成分间的均衡释放性。结果 以改良桃胶和HPMC制备的喘平方缓释片与溶出介质接触后,0.5 h开始有少量颗粒脱落,随着时间的推移,颗粒脱落明显。二者相比,改良桃胶制备的喘平方缓释片均衡释放性更佳(麻黄碱K为12.18、伪麻黄碱K为12.30、东莨菪碱K为12.40)、颗粒脱落更快(1 h明显可见)、粒径更大(D50为53.37~70.33μm、D90为100.3~196.5μm)、脱落颗粒载药量更多(麻黄碱30.63%、伪麻黄碱32.97%、东莨菪碱31.67%)、药物释放时间更长(60~120 min)。结论 脱落颗粒是喘平方缓释片(改良桃胶)多指标成分均衡释放的重要组成部分,是"溶蚀-溶散"药物释放模式的体现。
[Key word]
[Abstract]
Objective To study on the changes of shedding particles, drug loading and release of Chuanping Sustained-release Tablets (CST) which were made by the different sustained-release excipients in vitro, so as to elucidate the mechanism about balanced release of multi-marker components on Chinese materia medica compound sustained-release preparation. Methods Using Chuanping Prescription (Ephedra Herba and Datura Flos) as model drug, improved Peach Gum and HPMC was used as sustained release materials, the release test combinied with underwater video observation were applied to shot external forms at different time point, and the laser particle sizer was applied to determinate particle size, and HPLC was applied to determine the accumulated release rate of the index components (ephedrine, pseudoephedrine, and scopolamine) to calculate the cumulative release curve slope K value, and to evaluate the balance release of the different components. Results CST which were made by the improved peach gum and HPMC sustained-release excipient, which particles were dropped at 0.5 h after contacting the dissolution medium. At the same time, the particles were obviously shedding with the passage of time. In contrast, CST that was made by the improved peach gum, its balanced release of multi-marker components was better (K of ephedrine was 12.18, K of pseudoephedrine was 12.30, and K of scopolamine was 12.40), and particles dropped faster (it was significantly at 1 h), and particle size was bigger (D50 was 53.37-70.33 μm and D90 was 100.3-196.5 μm), and drug loading was more (ephedrine 30.63%, pseudoephedrine 32.97%, and scopolamine 31.67%), and release time of drug was longer (60-120 min). Conclusion The shedding particles were important part of balance release of multi-marker components about CST which was made by the improved peach gum sustained-release excipient, and also was the embodiment of the drug release mode of "corrosion-dissolution".
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[基金项目]
国家自然科学基金青年基金项目(81503260);国家自然科学基金面上项目(81373981)