醋酸亮丙瑞林聚乳酸-羟基乙酸共聚物微球的处方优化及评价

Prescription optimization and evaluation of leuprolide acetate PLGA microspheres

目的 对醋酸亮丙瑞林聚乳酸-羟基乙酸共聚物(PLGA)微球处方进行优化,以制备粒径较小,包封率较高的微球,并对其进行评价。方法 采用W1/O/W2乳化溶剂挥发法制备醋酸亮丙瑞林PLGA微球,以理论载药量、PVA体积分数、水油相比例为自变量,以粒径、包封率为响应指标,通过Box-Behnken响应面法优化处方,并对最优处方进行粒径、载药量、包封率、表面形态、药物稳定性、体外加速释放、生物相容性等评价。结果 微球最优处方参数为:理论载药量为7.59%,PVA体积分数为2%,水油比为200∶1。最优处方下得到的微球粒径为(20.81±1.34)μm,包封率为(95.88±1.56)%。扫面电镜显示微球呈球形,表面圆整,且孔道较多;高效液相色谱图和圆二色谱图显示微球具有良好的药物稳定性;体外加速释放结果显示药物以一级释药模型释放;HE染色结果显示微球具有良好的生物相容性。结论 通过Box-Behnken响应面法优化微球处方合理可行,所制备出的微球粒径较小,包封率较高,并具有良好的药物稳定性及生物相容性。

Objective To optimize and evaluate the formulation of leuprolide acetate PLGA microspheres, and prepare microspheres with smaller particle size and higher encapsulation efficiency.Methods Leuprolide acetate PLGA microspheres were prepared by W1/O/W2 emulsification solvent evaporation. The formulation was optimized by Box-Behnken response surface method with theoretical drug loading, PVA volume fraction, water-oil ratio as the independent variables, particle size and encapsulation efficiency as the response indicators, and characterized by particle size, drug loading, entrapment efficiency, surface morphology, drug stability, in vitro accelerated release and biocompatibility. Results The optimal formulation parameters of microspheres were as follows:theoretical drug loading at 7.59%, PVA volume fraction at 2%, and water-oil ratio at 200∶1. The particle size of the microspheres obtained under the optimal prescription was(20.81±1.34) μm, and the encapsulation efficiency was(95.88±1.56)%. The scanning electron microscopy showed that the microspheres had round surface and dense pore. HPLC and CD showed that the microspheres had good drug stability. In vitro accelerated release results showed that the drug was released with first-order drug release model. HE staining showed that the microspheres had good biocompatibility.Conclusion It is reasonable and feasible to optimize the formulation of microspheres by BoxBehnken response surface method, and the microspheres have small particle size, high encapsulation efficiency, good drug stability and biocompatibility.