吲哚美辛眼用缓释微球的制备及性能评价

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

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。

OBJECTIVE To obtain sustainedrelease 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 micro spheres was positive. The blank microspheres showed no sign of toxicity. CONCLUSION Indomethacin PLGA/Eudragit RS 100 mi crospheres have a better clinical application prospect due to its high entrapment efficiency, narrow distribution, slow release and ocular safety.