恩替卡韦-PLGA缓释微球的处方优化及体外释药研究  

Study on the Formulation Optimization of Entecavir PLGA Sustained-release Microspheres and Its Drug Release in vitro

作　　者：林凤云[1,2] 罗易[3] 何雄伟[4] 

机构地区：[1]重庆医药高等专科学校药学院,重庆401331 [2]重庆市药物制剂工程技术研究中心,重庆401331 [3]重庆市第九人民医院药剂科,重庆400700 [4]重庆市第九人民医院临床药学研究室,重庆400700

出　　处：《中国药房》2016年第25期3549-3552,共4页China Pharmacy

基　　金：重庆市医学科研计划项目(No.2013-2-153);重庆医药高等专科学校校级科研计划项目(No.ygz2013101)

摘　　要：目的:优化恩替卡韦聚乳酸-羟基乙酸共聚物(PLGA)缓释微球的处方,并考察其体外释药特性。方法:采用乳化-溶剂挥发法制备恩替卡韦-PLGA缓释微球;以微球的包封率、载药量的综合评分为评价指标,设计正交试验优化投药量、药物-PLGA质量比、PLGA质量浓度、油相-水相体积比、聚乙烯醇(PVA)浓度,并进行验证试验;考察所制微球形态、粒径及体外释药情况(Q)。结果:最优处方为恩替卡韦20 mg、恩替卡韦-PLGA质量比1∶10、PLGA质量浓度200 mg/ml、油相-水相体积比1∶10、PVA浓度2%。所制恩替卡韦-PLGA缓释微球的包封率为(86.52±3.25)%,载药量为(18.36±1.37)%,RSD均小于5.0%(n=3);其表面光滑圆整,平均粒径为58.35μm;Q_(10h)、Q_(96h)、Q_(360h)分别为9.6%、42.9%、89.6%,体外释药符合Higuchi模型(r^2=0.965 8)。结论:优化处方所制恩替卡韦-PLGA缓释微球的缓释性能良好。OBJECTIVE： To optimize the formulation of entecavir PLGA sustained-release microspheres, and explore its drug release in vitro. METHODS： PLGA sustained-release microspheres was prepared by emulsification-solvent evaporation method. Us- ing composite score of entrapment efficacy and drug loading as indexes, orthogonal test was designed to optimize drug amount, drug-PLGA mass ratio, PLGA mass concentration, oil phase-aqueous phase volume ratio and polyvinyl alcohol （PVA） concentra- tion; and validation test was also conducted. The prepared microsphere morphology, particle size and durg release in vitro were de- tected. RESULTS： The optimized formulation was entecavir 20 mg, entecavir-PLGA mass ratio 1 ： 10, PLGA mass concentration 200 mg/ml, oil phase-aqueous phase volume ratio 1 ： 10, and PVA concentration 2% ; entrapment efficacy was （86.52 ±3.25）%, drug loading was （18.36 ± 1.37）%, RSDs were lower than 5.0% （n=3） ; it was round and smooth in appearance with average par- ticle size of 58.35 μm; Q1oh, Q96h and Q360h were 9.6%, 42.9% and 89.6%, and the drug release in vitro fitted to Higuchi model （r2= 0.965 8）. CONCLUSIONS： Entecavir PLGA sustained-release microspheres prepared by optimized formulation has good sus- tained-release performance.

关 键 词：恩替卡韦 缓释微球 聚乳酸-羟基乙酸共聚物 体外释药 正交试验 制备 处方优化 

分 类 号：R943[医药卫生—药剂学]