甲睾酮聚乳酸缓释微球的制备

Preparation of Methyltestosterone Polylactic Acid Sustained-release Microspheres

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（MT-PLA-MS）.METHODS：MT-PLA-MS was prepared by emulsification solvent evaporation method,and single factor test was conducted to select molecular weight and concentration of polylactic acids and ratio of drug to PLA.Orthogonal test was used to optimize temperature,rotation speed,concentration of polylactic acids and ratio of drug to PLA.The appearance,particle size,drug-loading amount,encapsulation coefficency and 168 h accumulative drug-releasing rate in vitro were investigated,and zero-order,first-order,Higuchi and two-phase dynamic equations of microspheres were fitted.RESULTS：The optimal condition was as follows：molecular weight of polylactic acids of 110 thousand,temperature of 30 ℃,rotation speed of 500 r·min-1,concentration of polylactic acids of 0.1 g·mL-1 and ratio of drug to PLA of 1：5.Prepared microspheres were round with smooth surface.Mean particle size was（2.5±0.2）μm,drug-loading amount was 6.18% ～6.62%,encapsulation coefficency was 89.9% ～91.3% and 168 h accumulative drug-releasing rate was（41.8±0.1）%.Two-phase dynamic equation of microsphere was fitted for microspheres（r=0.994 5）.CONCLUSION：The preparation technology is stable and microspheres exhibit good sustained-release capacity.