SPG膜乳化法制备粒径均匀的布比卡因P(L)GA微球

Uniform bupivacaine PL(G)A microspheres for sustained release prepared by SPG membrane emulsification method

目的以酰胺类局部麻醉药布比卡因为模型药物,生物可降解的P(L)GA为骨架材料,采用SPG膜乳化法制备均一粒径、高载药量的缓释布比卡因微球。方法以微球粒径、表面形态、载药量和包封率为考察指标,筛选微球制剂处方,考察微球的体外释放行为并探讨药物释药机制。结果采用孔径40μm的SPG膜所制备的布比卡因P(L)GA微球的粒径均在15~20μm内,粒径分布均匀;偏光显微镜观察和XRPD分析结果表明,药物以晶体形态存在于微球内部;影响微球释放的主要因素为投药量、外水相体积及载体类型;当投药量的质量分数为75%、外水相体积100 mL时制备的布比卡因PLA微球具有相对理想的药物释放行为;Ritger-Peppas拟合结果表明,布比卡因以扩散方式从微球中释放。结论这种高载药量、粒径均匀的布比卡因缓释微球可望应用于临床的术后镇痛。

Objective The aim of this study is to prepare biodegradable P(L)GA microspheres embedded with high content of bupivacaine, an amide type of local anesthetics by the Shirasu porous glass(SPG) membrane emulsification technique, for sustained drug release. Method The formulation was screened by evaluating particle size, surface morphology, drug loading and entrapment efficiency, and the in vitro drug release behavior and the release mechanism were investigated. Result Polarizing microscope observation and XPRD analysis indicated that bupivacaine existed as crystal in the uniform microspheres(15-20 μm) prepared by the SPG membrane with pore size of 40 μm. The key factors which affect the release of drug in cludes feed ratio of drug to polymer, volume of aqueous phase and type of P(L)GA. When the feed ratio of drug to polymer was 75% and aqueous phase volume was 100 mL, the drug loaded PLA microspheres exhibited sustained drug release behavior in vitro. Ritger-Peppas equation was introduced to fit the release profiles, and the result suggested that the release of bupivacaine from microspheres followed a diffusion controlled mechanism. Conclusion Uniform-sized PLA microspheres of high drug loading was prepared for sustained drug release, which provides great potential for the treatment of postoperative pain.