磷酸川芎嗪星型聚乳酸缓释微球的制备与体外释放研究

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

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,0~48h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。

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.