Box-Behnken效应面法优化塞来昔布微球制备工艺

Optimization of preparation process of celecoxib microsphere by Box-Behnken response

目的:制备塞来昔布聚乳酸-羟基乙酸共聚物(PLGA)载药微球,优化其处方和制备工艺,考察其体外释药行为。方法:分别以油相中PLGA浓度、水相PVA浓度和油/水相体积比为考察因素,以包封率为考察指标,采用Box-Behnken效应面法优化塞来昔布微球的处方和工艺;透析袋法评估其体外释放能力。结果:塞来昔布PLGA微球的最佳处方工艺条件为:PLGA浓度75 g·L^-1,水相PVA体积分数1.5%,油/水相体积比1∶30。所制备的微球形态圆整,大小均一,实测包封率为66.1%,与预测值67.3%相比,偏差为1.8%。最优处方体外14 d累积释药56%,体外释放曲线符合Higuchi方程。结论:Box-Behnken效应面法简便可行,可用于优化塞来昔布PLGA微球的制备,微球体外释放具有缓释效果。

OBJECTIVE To prepare celecoxib polylactic-co-glycolic acid(PLGA)drug-loaded microspheres,optimize the formulation and preparation process,and investigate its release behavior in vitro.METHODS The influence factors included the concentration of PLGA in organic phase,the concentration of PVA in water phase and the volume ratio of organic phase to water phase were optimized by Box-Behnken response surface method with the entrapment efficiency as the evaluation parameters.The release capacity was evaluated by dialysis bag experiment.RESULTS The optimal formulation and process parameters were as follows:the concentration of PLGA in organic phase was 75 g·L^-1;the concentration of PVA was 1.5%,and the volume ratio of organic phase to water phase was 1∶30.The microspheres prepared under these conditions were round and uniform in size.The measured encapsulation efficiency was 66.1%,and the deviation was 1.8%compared with the predicted value of 67.3%.The accumulated release percentage of optimized microspheres was 56%during 14 days,and the release curves could be fitted with Higuchi equation.CONCLUSION The Box-Behnken response surface method is simple and feasible,and can be used for drug loading process optimization of celecoxib PLGA microsphere.The obtained microspheres have a good prolonged release effect in vitro.