盐酸索他洛尔生物粘附微球的制备及体外释药特性研究

Preparation and Drug Release Profiles in vitro of Sotalol Bioadhesive Microspheres

目的:制备盐酸索他洛尔生物粘附微球,考察其体外释药特性并评价其粘附性能。方法:应用正交试验筛选盐酸索他洛尔生物粘附微球的最佳处方,采用高效液相色谱法测定盐酸索他洛尔生物粘附微球的含量与释放度,选用滞留率为指标考察微球的粘附特性。结果:盐酸索他洛尔生物粘附微球的最佳处方为盐酸索他洛尔投药量占处方组成的30%,分散相与连续相比为70%,司盘80用量为9.0g;体外释药试验结果表明盐酸索他洛尔生物粘附微球30min累积释药百分率达30%,4h释药达90%;离体法与在体法测得微球胃黏膜上的滞留率分别为(87.6±2.8)%与(60.2±9.8)%。结论:盐酸索他洛尔生物粘附微球处方设计合理,制备工艺简单,与盐酸索他洛尔普通片相比,盐酸索他洛尔生物粘附微球具有一定缓释特性,且其在离体与在体模型中粘附性能良好。

Objective： To prepare sotalol bioadhesive microsphere and investigate its drug release profiles in vitro and mucoadhesive characteristics. Method： The orthogonal design method was used to select the best formulation of sotalol bioadhesive microsphere. The content of sotalol in bioadhesive microspheres and drug release percentage were analyzed by HPLC, and its mucoadhesive property was studied using stagnation percentage as the content index. Result： The optimum formulation of sotalol adhesive microsphere was consisted of sotalol （30%）, phase ratio of diperse and continuous phase （70%） and Span-80 （9.0g）. The release profiles of sotalol demonstrated that the accumulated drug release percentage at 30 min and 4 h were 30% and 90%, respectively. Mucoadhesive property test results showed that stagnation percentages of sotalol bioadhesive microspheres in vitro and in vivo were （87.6 ± 2.8 ） % and （60.2 ± 9.8 ） %, respectively. Conclusion： The performulation of sotalol adhesive microsphere is reasonable and the preparation tech- nology is simple. Compared with sotalol compressed tablets, sotalol bioadhesive microspheres possess sustained drug release and sound adhesiveness in vitro and in vivo.