氢化可的松结肠靶向片包衣处方筛选及其释放机制研究

目的:筛选氢化可的松结肠靶向片的包衣处方,并考察其释放机制。方法:采用星点设计-效应面法优化氢化可的松结肠靶向片的包衣处方。以明胶-壳聚糖包衣(GC)层和聚丙烯酸树脂Eudragit L100包衣(E)层的包衣增质量为自变量,以靶向片在人工胃液、人工小肠液及人工结肠液的累积释放度(Q2 h、Q4 h、Q24 h)为因变量,分别进行多元线性和非线性拟合。根据绘制效应面选取最佳处方,并通过数学原理和相关模型探讨其释放机制。结果:GC层及E层包衣增质量最佳值分别为4%和20%;制备的3批氢化可的松结肠靶向片的平均Q2 h、Q4 h、Q24 h分别为0.16%、4.7%、93.35%;其释放符合一级动力学模型(r=0.984 5)。结论:根据筛选的包衣处方制备的氢化可的松结肠靶向片的体外释放符合缓释制剂要求。

Selection of Coating Formulation and Release Mechanism of Hydrocortisone Colon-targeted Tablets

OBJECTIVE： To select the coating formulation of Hydrocortisone colon-targeted tablets, and to investigate the re- lease mechanism of the tablet. METHODS： The coating formulation of Hydrocortisone colon-targeted tablets was optimized by cen- tral composite design and response surface method. Using coating weight gain of gelatin-chitosan coating （GC） layer and polyacryl- ic resin Eudragit L100 coating （E） layer as independent variable, the accumulative releases rate of the tablet in the artificial gastric juice, artificial intestinal juice and colonic juice （Q2h, Q4h, Q24h） as dependent variables, multi-linear and non-linear models were used to estimate the relationship between the dependent and independent variables, and the optimal formulations were selected ac- cording to response surface. And the release mechanism was investigated by the mathematics principle and relative model. RE- SULTS： The optimal coating weight gain of GC layer and E layer were 4% and 20%, respectively. Average Q2h, Q4h, and Q24h, of 3 batches of the tablet were 0.16%, 4.7% and 93.35%. The release profile of optimal formulation fitted to the first-order kinetic mod- el （r= 0.984 5）. CONCLUSIONS： The in vitro drug release of the tablet prepared by selected coating formulation conforms to the requirements of the sustained-release formulation.