布比卡因缓释微球的制备及体外释药特性评价

Preparation of sustained-release poly(D,L-lactide-co-glycolide)microspheres containing bupivacaine and the evaluation of drug release in vitro

目的研究布比卡因缓释微球制备方法并对其体外释药特性进行评价.方法采用紫外分光光度法测定布比卡因微球载药量、包封率;采用HPLC法测定微球体外释放;通过正交设计优选微球制备工艺;以乳酸-羟基乙酸共聚物为载体,使用乳化-溶剂挥发法制备布比卡因微球;用扫描电镜观察所得微球的粒径和形态;通过体外释药实验考察布比卡因乳酸-羟基乙酸共聚物微球的缓释作用.结果微球载药量、包封率和体外释放的测定方法符合方法学要求;按照优选处方制备所得的微球为圆整球体,表面多孔,呈蜂窝状,粒径50～100 μm之间的微球占80%;体外释放符合Ritger-Peppas方程,t1/2=242.05 h.结论乳化-溶剂挥发法适用于布比卡因乳酸-羟基乙酸共聚物微球的制备,所制得的微球形态圆整,在体外具有明显缓释作用.

Objective To prepare sustained-release poly（ D, L-lactide-co-glycolide）（PLGA）microspheres containing bupivacaine and study drug release in vitro. Methods Ultraviolet（UV）spectrophotomatry method was used for determination of the drug loading percent and drug entrapment efficiency of PI.GA microspheres containing bupivacaine. High-performance liquid chromatography method with UV detector was applied to detect drug release of the preparation in vitro. The orthogonal design was used to optimize the preparation technology of the microspheres. The microspheres containing bupivacaine were prepared by the emulsification-solvent evaporation method using PI.GA as carriers and their release characteristics were measured in vitro. Results The analytical methods for determination of the drug loading percent, drug entrap- ment efficiency and drug release of microspheres in vitro were proved to be sensitive, precise and reliable. PLGA microspheres containing bupivacaine were globular and had porous surface like “honeycomb”. The yield of microspheres with diameter between 50 - 100μm was more than 80 %. The in vitro release profiles could be expressed by Ritger-Peppas equation with t 1/2 = 242.05 h. Conclusions The emulsification-solvent evaporation method is applicable for the preparation of PLGA microspheres containing bupivacaine. It is shown that the microspheres containing bupivacaine have good appearance and significant in vitro sustained-release characteristics.