新型利培酮PLGA微球的制备及体外释放研究

 目的 制备新型利培酮微球,并快速评价微球的体外释放性质。方法 采用O/W乳化溶剂挥发法制备微球,研究PLGA浓度、乳化均质转速、油相与水相比例等对微球粒径和包封率的影响。通过升高释放介质温度建立体外释放加速评价方法。结果 在37 ℃ pH 7.4 PBS中,利培酮微球以零级释放模式缓释15 d,快速释放的时间与上市利培酮微球基本一致而无延滞期。采用45 ℃加速释放可提高释放速度5倍,在3 d内完成评价,加速释放评价与长期释放相关性好。结论 本实验所制备的利培酮微球,可开发为释放两周的制剂。由于无延滞期,在临床使用和提高患者顺应性上比已上市产品更具优势。加速评价方法可对产品进行快速质量控制。

Preparation and in Vitro Release of Novel Risperidone-Loaded PLGA Microspheres

OBJECTIVE To prepare novel risperidone-loaded PLGA microspheres and evaluate the in vitro release characters of this microspheres. METHODS Risperidone-loaded PLGA microspheres were produced by o/w emulsion solvent extraction/evaporation technique. The influences of preparation parameters on particle size and encapsulation efficiency were investigated, such as PLGA concentration, homogenization speed at the emulsion stage, and ratio of o/w phase, et al. The method for accelerated evaluation of in vitro release was also investigated via evaluating the release properties at different temperatures. RESULTS In vitro release of risperidone-loaded PLGA microspheres in pH 7.4 PBS at 37 ℃ was up to 15 d following Zero-order model. The released time was comparable with the risperidone microspheres marketed by Johnson & Johnson (brand name is Risperdal CONSTA but without lag phase. Complete release at 37 ℃ was shortened from 15 d to 3 d at 45 ℃. CONCLUSION Risperidone-loaded PLGA microspheres in this study could be developed as two-week formula. The formula could be released constantly without lag phase. It is helpful for improving the patient′s compliance and modifying clinical dosage. Accelerated in vitro release at 45 ℃ could be completed within 3 days. It is useful in the prediction of long term release and may serve as a quality control tool for the release of commercial batches.