吲哚美辛眼用缓释微球的制备及性能评价

 目的 制备吲哚美辛聚乳酸-羟基乙酸共聚物（PLGA）/Eudragit RS 100眼用缓释微球，并进行表征。方法 采用O/W溶剂挥发法制备吲哚美辛PLGA/Eudragit RS 100微球，对微球的表面形态、载药量、包封率、体外释放特点、粒径、有机溶剂残留量、表面电位进行了表征分析，使用人视网膜色素上皮细胞（RPE cells）评估空白微球的细胞毒性。结果 载体材料PLGA与Eudragit RS 100质量比为1∶3的吲哚美辛微球，电镜观察颗粒分布均匀，表面光滑；平均粒径为（1 676.4±739.5）nm；载药量为（18.79±0.19）%，包封率为（98.25±2.11）%，第1天存在突释，随后可以缓慢释放一个月左右；有机残留量平均为（267.33±13.57）ppm；空白微球表面电位为正电荷；空白微球无细胞毒性。结论 吲哚美辛PLGA/Eudragit RS 100眼用缓释微球具有包封率高，粒径窄，体外释放缓慢，安全性好等特点，具有很好的临床应用前景。

Preparation and Physicochemical Evaluation of Indomethacin Sustained-Release Microspheres for Ophthalmic Delivery

OBJECTIVE To obtain sustained-release indomethacin PLGA/Eudragit RS 100 microspheres for ophthalmic application and to evaluate its quality. METHODS The microspheres were prepared by O/W solvent evaporation using PLGA and Eudragit RS 100. The morphological， drug content， entrapment efficiency， release behavior， particle size， residual organic solvent， Zeta potential of indomethacin PLGA/Eudragit RS 100 microspheres were determined； meanwhile， the cytotoxicity of blank microspheres was evaluated using PRE cells. RESULTS Indomethacin microspheres containing PLGA and Eudragit RS 100 at the weight ratio of 1∶3 had even particle size distribution， and their surfaces were smooth under scan electronic microscope； and the mean diameters were (1 676.4±739.5) nm. The drug content and entrapment efficiency of the microspheres were (18.79±0.19) % and (98.25±2.11) %， respectively. Indomethacin was released slowly for a month from the microspheres， though burst release was observed within 24 h. The mean residual organic solvent was (267.33±13.57) ppm. The zeta potential of all blank PLGA/ Eudragit RS 100 microspheres was positive. The blank microspheres showed no sign of toxicity. CONCLUSION Indomethacin PLGA/Eudragit RS 100 microspheres have a better clinical application prospect due to its high entrapment efficiency， narrow distribution， slow release and ocular safety.