醋酸阿比特龙缓释微球的制备及其体内外释药特性的考察  

Preparation of abiraterone acetate microspheres and their drug release characteristics in vitro and in vivo

作　　者：刘茹 杜丽平 张丽 郝贵周 孙勇[1] LIU Ru;DU Li-ping;ZHANG Li;HAO Gui-zhou;SUN Yong(Qingdao University,Qingdao Shandong 266071;Shandong New Times Pharmaceutical Co.,Ltd.,Linyi Shandong 273400)

机构地区：[1]青岛大学,山东青岛266071 [2]山东新时代药业有限公司,山东临沂273400

出　　处：《中南药学》2023年第3期582-588,共7页Central South Pharmacy

摘　　要：目的制备一种具有较好缓释效果的醋酸阿比特龙微球,并确定其最佳处方与工艺。方法以可生物降解的聚乳酸-羟基乙酸(PLGA)为载体材料,二氯甲烷(DCM)为有机溶剂,采用O/W型乳化-溶剂挥发法制备醋酸阿比特龙微球,扫描电子显微镜观察其外观形态,激光粒度仪测定其粒径,高效液相色谱法测定其载药量和包封率,气相色谱法测定DCM残留量,摇床法考察载药微球的体外释药特性,SD大鼠肌内注射考察微球的体内缓释效果。结果醋酸阿比特龙微球呈圆整的球形粒子,平均粒径43.7μm,载药量39.27%,包封率98.15%,DCM残留量0.054%。体外加速释放结果表明药物释放以扩散机制为主,释药周期可稳定维持11 d,累积释药度为80.86%;体内释药周期可维持16 d。结论制备的醋酸阿比特龙微球能够克服由于食物摄入引起的药物暴露量增加、血药浓度不稳定的问题,减少给药次数,实现了较好的缓释效果,为其后续的产业化提供了一定的数据支持,对其他小分子药物微球的研发具有一定的参考价值。Objective To prepare abiraterone acetate microspheres with good sustained release and determine its optimal prescription and process.Methods Abiraterone acetate microspheres were prepared by O/W emulsion-solvent evaporation method using biodegradable polylactic acid-glycolic acid(PLGA)as the carrier material and dichloromethane(DCM)as the organic solvent.The appearance was observed by SEM.The particle size was measured by laser particle size analyzer.The drug loading and encapsulation efficiency were determined by HPLC.The DCM residue was determined by GC.The in vitro release characteristics were investigated by shaking table method and the sustained release effect in vivo by intramuscular injection in SD rats.Results Abiraterone acetate microspheres were spherical particles with an average particle size of 43.7μm,drug loading of 39.27%,encapsulation efficiency of 98.15%,and DCM residue of 0.054%.The accelerated in vitro release showed that the drug release was mainly due to the diffusion,with the release cycle stably maintaining for 11 days,and a cumulative release of 80.86%.The drug release cycle in vivo might last 16 days.Conclusion Abiraterone acetate microspheres can overcome the problems of increased drug exposure and unstable blood concentration caused by food intake.Good sustained release may be achived by reducing the number of administrations,providing reference for the development of other small molecule drug microspheres.

关 键 词：醋酸阿比特龙 缓释微球 乳化溶剂挥发法 体外释药 体内释药 

分 类 号：R94[医药卫生—药剂学] R96[医药卫生—药学]