胶束増溶硝苯地平缓释微球的制备及体内药动学研究

 目的 利用单甲氧基聚乙二醇接枝玉米朊（mPEG-g-Zein）在水中能够自组装成胶束的原理来增加模型药物硝苯地平（NFP）的溶解度，以聚乙烯醇（PVA）为囊材制备成包裹硝苯地平-单甲氧基聚乙二醇接枝玉米朊纳米胶束的微球，并考察其体内外释放情况。方法 采用悬浮界面交联法一步制备纳米胶束硝苯地平-单甲氧基聚乙二醇接枝玉米朊-微球，考察其粒径、载药量、包封率和体外释放情况。用高效液相色谱法（HPLC）测定大鼠口服硝苯地平微球(受试制剂)和硝苯地平片(参比制剂)后不同时间点血浆中硝苯地平的浓度，计算药物动力学参数和相对生物利用度。结果 该微球平均粒径为22 μm（其内包裹的纳米胶束平均粒径为200 nm），载药量、包封率和体外累计释药量分别为15.16%、85.8%、93.8%，相对生物利用度为166%。结论 该硝苯地平微球外观圆整、粒径分布均匀、体外释药缓释效果明显，且相对生物利用度高。

Preparation of Sustained-Release Microspheres of Nifedipine with Micelle Solubilization and Its in Vivo Pharmacokinetic Study

OBJECTIVE To prepare nifedipine-mPEG-g-Zein sustained-release microspheres， making use of the mechanism that hydrophilic mPEG-g-Zein can be self-assembled into micelles in the water to increase the solubility of the poorly water-soluble drug nifedipine， and to examine its in vitro and in vivo release behaviors. METHODS The nifedipine-mPEG-g-Zein microspheres were prepared by the method of suspension interfacial crosslinking. Polyvinyl alcohol (PVA) was used as the capsule material. The particle size， drug-loading rate， encapsulation efficiency and the total in vitro drug release were examined. The plasma levels of nifedipine at different time points were determined by HPLC after oral administration of a single dose of the self-made microspheres (test formulation) and marketed tablets (reference formulation) to mice. The pharmacokinetics and relative bioavailability were analyzed. RESULTS The average diameter of the microcapsules was 22 μm (in which the average particle size of nano-micelles was 200 nm)， and the drug loading， encapsulation efficiency， and the total in vitro drug release were 15.16%， 85.8% and 93.8%. The relative bioavailability the microspheres to the tablets was 166%. CONCLUSION The microspheres are round and the size distribution is uniform. Meanwhile， the in vitro release profile shows obvious sustained-release characteristics， and the relative bioavailability is increased.