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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 explore the feasibility of preparing gestodene / ethinyl estradiol compound microspheres for subcutaneous injection. Methods Lactate - glycolic acid copolymer (PLGA) as carrier material, gestodene and ethinylestradiol were used as model drugs. The microspheres were subcutaneously injected with emulsified solvent evaporation method to observe the surface morphology of microspheres. Preparation of microspheres stability, detection of microspheres of organic solvent residues and in vitro release characteristics. Results The entrapment efficiency of gestodene and ethinyl estradiol in the microspheres was (69.9 ± 6.6)% and (60.5 ± 1.5)%, respectively. The morphology of the microspheres was good with the narrow particle size distribution and the average particle size was (65.62 ± 4.56) μm. The residues of organic solvents in the microspheres were (154.84 ± 16.84) mg.L-1. During in vitro release, the two drugs sustained and stable release for 30 days. The in vitro release behavior of the two drugs was in accordance with Weibull equation, The release equations of ketones and ethinyl estradiol were as follows: ln [ln1 / (1-F (t)] = 0.625 8lnt- 1.826 (r = 0.992 1) and ln [ln1 / (1-F 0.855 2lnt-2.850 1 (r = 0.991 4). The prepared microspheres were unstable under high temperature and light conditions, unstable at room temperature for a long time, but stable under light and cold conditions.Conclusion The preparation process was stable , The encapsulation efficiency of the microspheres is high, the particle size is uniform, the residue of the organic solvent conforms to the national standard, the drug release is stable and the drug release time is longer, and further in vivo studies can be conducted.