同时包载孕二烯酮和炔雌醇的PLGA微球的制备

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

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。

Objective To study the practicability for the preparation of subcutaneous injected microspheres loaded with gestodene and ethinyl estradiol. Methods Using poly（d, 1-1actide-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 In （ln1/（ 1-F （ t ）） = 0. 6258lnt-1. 826 （ R^2 = 0. 992 1 ） and ln（ln1/（1-F（t ） ） = 0. 85521nt-2. 8501 （R^2 = 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