磷酸川芎嗪星型聚乳酸缓释微球的制备与体外释放研究

目的 制备磷酸川芎嗪星型聚乳酸载药微球，研究制备工艺参数对载药微球的药物包封率的影响，并对其体外释放特性进行表征。方法 以星型聚L-乳酸(sPLLA)为聚合物基材，采用复乳-溶剂挥发法制备磷酸川芎嗪(LP)星型聚乳酸载药微球(sPLLA/LP)，采用正交试验优化处方，研究sPLLA/LP的体外缓释特性，并用FT-IR和SEM对微球进行表征。结果 通过极差分析与方差分析建立sPLLA/LP的药物包封率与制备工艺参数之间的关系，并在此基础上遴选出优化工艺。LP与sPLLA结合良好，sPLLA/LP微球缓释7 d后，sPLLA出现部分降解。采用优化工艺所制备的sPLLA/LP微球具有良好的缓释效果，SEM分析与缓释模型的拟合结果表明，0～48 h阶段的释药机制为药物扩散和聚合物降解协同作用；48～144 h阶段则主要为药物扩散释药。结论 采用复乳-溶剂挥发法制备的sPLLA/LP微球的药物包封率较高、体外释药平稳。

Preparation of sPLLA/LP microspheres and its in vitro release properties

Objective To prepare star-shaped poly (L-lactic acid) loaded ligustrazine phosphate (sPLLA/LP) microspheres and study the influence of preparation technologies on drug encapsulation efficiency of sPLLA/Lp microspheres and its in vitro drug release. Methods sPLLA/LP Microspheres were prepared using the method of solvent evaporation and W/O/W emulsion. To optimize the preparation technology, an orthogonal design was applied. FT-IR and SEM were applied to characterize sPLLA/LP microspheres. Results The optimized preparation technology was obtained based on range analysis and variance analysis. LP could combine with sPLLA well, and part of sPLLA were degraded after 7 d in vitro release. The release mechanism of sPLLA/LP microspheres was non-Fickian diffusing for the first 0-48 h, i.e., the synergetic effect of polymer degradation and drug diffusing, and Fickian diffusing mechanism for the next 48-144 h. Conclusion The results show that the drug encapsulation efficiency of sPLLA/LP microspheres is higher, with the smooth and steady LP release from the microspheres.