同时包载孕二烯酮和炔雌醇的PLGA微球的制备

目的探索制备皮下注射用孕二烯酮/炔雌醇复方微球的可行性。方法以乳酸-羟基乙酸共聚物共聚物(PLGA)为载体材料,孕二烯酮、炔雌醇为模型药物,采用乳化溶剂挥发法制备皮下注射用复方微球,观察微球表面形态,检测所制微球的稳定性,检测微球的有机溶剂残留和体外释放特性。结果所得微球中孕二烯酮和炔雌醇的包封率分别为(69.9±6.6)%和(60.5±1.5)%;微球形态良好,粒径分布窄,平均粒径为(65.62±4.56)μm;微球中有机溶剂残留为(154.84±16.84)mg.L-1;体外释放过程中,2种药物能够持续稳定释放30 d,两药的体外释放行为符合Weibull方程,孕二烯酮和炔雌醇的释药方程分别为:ln[ln1/(1-F(t)]=0.625 8lnt-1.826(r=0.992 1)和:ln[ln1/(1-F(t)]=0.855 2lnt-2.850 1(r=0.991 4);制备的微球在高温、光照条件下均不稳定,在常温下长时间放置也不稳定,但在避光冷藏条件下稳定。结论所用制备工艺稳定,微球包封率较高,粒度均匀,有机溶剂残留符合国家标准,释药平稳,释药时间较长,可以进行进一步的体内研究。

Preparation of the PLGA microspheres loaded with both gestodene and ethinyl estradiol

Objective To study the practicability for the preparation of subcutaneous injected microspheres loaded with gestodene and ethinyl estradiol. Methods Using Poly (d, l-lactide-co-glycolide) (PLGA) as carrier material, Gestodene and ethinyl estradiol as model drugs, injected microspheres were prepared through emulsion-evaporation method. The resulted microspheres were observed, and the stability, organic solvent residue and release behavior were also investigated. Results The loading efficiency of gestodene and ethinyl estradiol were 69.9±6.6% and 60.5±1.5%, respectively. The microspheres were well sphere-shaped, and the particle size distribution was very narrow, and the mean particle size was 65.62±4.56 μm. As a result of the release testing, the release process of both the drugs could last 30 days, and the release behaviors were qualified for Weibull equation, which should be ln(ln1/(1-F(t))=0.625 8lnt-1.826 (R2=0.992 1) and ln(ln1/(1-F(t))=0.8552lnt-2.850 1 (R2=0.991 4), respectively. The prepared microspheres were not stable when they were stored at high temperature and lighting condition for a long period, neither for long time storage in room temperature, but stable in cool and dark place. Conclusions The preparation condition is stable; the loading efficiency is relatively high; particle size is uniform; the organic residue is qualified for the national standard; release behavior is stable and the process is quite long. The further study should be carried on.