超微粒制备系统制备利培酮长效注射微球

Risperidone-loaded long-acting injectable microspheres prepared by ultra-fine particle processing system

目的:制备利培酮长效注射微球并进行体外释药动力学考察。方法:选用聚乳酸-羟基乙酸共聚物[poly(D,L-lactic-co-glycolic acid),PLGA]为载体,采用新型超微粒制备系统制备利培酮PLGA微球。以转碟上聚合物析出量、丝状物的形成和微粒表面形态为考察指标单因素实验优化制备工艺参数及处方;观察微球表面形态,测定其粒径、包封率、考察其体外释药动力学。结果:20%和30%载药量的微球表面均光滑圆整,分散性好;其包封率分别为94.7%和93.94%,中值粒径分别为31.65和28.13μm;持续释药时间均可达16 d,释放数据用释放动力学方程拟合符合一级和Higuchi方程。20%载药量微球1 h释药率仅为4.2%,突释率低,且其释放速率和释放时间与市售利醅酮微球(恒德)快速释放期基本一致而无延滞期。结论:超微粒制备系统(UPPS)可单步骤制备长效微球,工艺稳定,简单可行,有望成为一种适合工业微球制备技术。UPPS制备的20%载药量微球可开发为释放2周的制剂,由于无释放延滞期,将比市售品更具临床优势。

Objective：To prepare risperidone-loaded long-acting injectable PLGA microspheres and study its drug release dynamics in vitro.Methods：The microspheres were prepared by a novel ultra-fine particle processing system with poly（D,L-lactic-co-glycolic acid） as drug carrier.The process parameters and formulations were optimized by using single factor test with the amount of polymer deposited on the disk,formation of silk-shaped materials and appearances of microparticles as the indexes.The characteristics of the microspheres were evaluated by appearances,particle size,encapsulation efficiency and in vitro release.Results：The encapsulation efficiency of 20% and 30% drug-loaded microspheres,which were well dispersed and spherical with smooth surfaces,were 94.7% and 93.94% with mean diameter of 31.65 μm and 28.13 μm,respectively.The drug release profiles in vitro demonstrated a sustained release for 16 days and were fitted by first-order and Higuchi kinetics model.The drug release of 20% drug-loaded microspheres was only 4.2% at 1 h due to low initial burst release.The release rate and time were comparable with the marketed risperidone microspheres（Risperdal CONSTA） but without lag phase.Conclusion：The preparation of drug-loaded microspheres by UPPS is single-step,highly reproducible,simple and feasible,which may be suitable for large-scale manufacture.20% drug-loaded microspheres prepared by UPPS can be developed as a formulation which can release drug constantly for two weeks without lag phase.It has more clinical advantages over commercially available microspheres.