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目的:制备甲睾酮聚乳酸缓释微球。方法:用乳化溶剂挥发法制备甲睾酮聚乳酸缓释微球。先设计单因素试验筛选制备微球的处方中的聚乳酸分子量、聚乳酸浓度、投药比(甲睾酮:聚乳酸);再采用正交试验优化制备微球的温度、转速、聚乳酸浓度、投药比。考察微球表面形态、粒径、载药量、包封率、168h体外累积释药率,并对微球的体外释药模型进行零级、一级、Higuchi、双相动力学方程拟合。结果:优选结果为聚乳酸分子量11万、温度30℃、转速500r·min-1、聚乳酸浓度0.1g·mL-1、投药比1:5。采用最佳工艺条件制备的微球形态圆整,平均粒径为(2.5±0.2)μm,载药量为6.18%～6.62%,包封率为89.9%～91.3%,168h体外累积释药率为(41.8±0.1)%,微球的体外释药符合双相动力学方程(r=0.9945)。结论:甲睾酮聚乳酸缓释微球制备工艺稳定,具有良好的缓释能力。
Objective: To prepare methyltestosterone polylactic acid sustained release microspheres. Methods: Methyltestosterone polylactic acid sustained-release microspheres were prepared by emulsifying solvent evaporation method. First design single factor test preparation of microspheres preparation of polylactic acid in the molecular weight, concentration of polylactic acid, dosing ratio (methyltestosterone: polylactic acid); orthogonal test to optimize the preparation of microspheres temperature, speed, concentration of polylactic acid, ratio. The surface morphology, particle size, drug loading, entrapment efficiency and cumulative drug release rate in vitro of the microspheres were investigated. The zero-order, first-order, Higuchi and biphasic kinetic equations were fitted to the microspheres in vitro. Results: The optimum conditions were as follows: the molecular weight of polylactic acid was 110,000, the temperature was 30 ℃, the rotational speed was 500r · min-1, the concentration of polylactic acid was 0.1g · mL-1 and the dosage was 1: 5. The morphology of the microspheres prepared by the best technological conditions was round and the average particle size was (2.5 ± 0.2) μm, the drug loading was 6.18% ~ 6.62%, the entrapment efficiency was 89.9% ~ 91.3% (41.8 ± 0.1)%. The in vitro release of microspheres was in accordance with the biphasic kinetic equation (r = 0.9945). CONCLUSION: Methyltestosterone polylactic acid sustained-release microspheres have stable preparation process and good sustained-release ability.