卡托普利缓释微球的制备及其性能研究

Preparation and Evaluation for Net-polymer Sustained-release Captopril/Chitosan-gelatin Microspheres

目的 制备卡托普利 /壳聚糖 -明胶网络多聚物缓释微球 (captopril/chitosan -gelatinnet -polymermicrospheres,Cap/CGNPMs) ,为改善Cap治疗效果 ,降低不良反应 ,并为开发理想的水溶性药物缓释系统提供实验依据和理论基础。方法 以壳聚糖和明胶为载体材料 ,采用乳化分散法制备Cap/CGNPMs ,紫外分光光度法和光学显微镜及电子显微镜对其性能进行研究。结果 Cap/CGNPMs外观完整致密 ,表面可看到许多微孔 ,无粘连 ,流动性很好 ,粒径分布范围主要在 2 2 0～ 2 80 μm。体外释药试验证明 ,Cap/CGNPMs与Cap普通片比较具有明显延缓Cap释放作用。微球的包封率、载药量和溶胀度及体外释药行为受工艺条件如投料比、交联剂组成等因素的影响。其中 ,投料比为 1∶4 ,交联剂配方 :For +TPP ,添加 0 .75 %微晶纤维素是Cap/CGNPMs制备最佳条件。结论 Cap/CGNPMs性能良好 ,制备工艺简单稳定 ,有望成为水溶性药物的理想缓释系统。

Aim To prepare captopril/chitosan-gelatin net-polymer microspheres (Cap/CGNPMs) in order to improve the therapeutic efficiency,decrease the side effects of captopril (Cap) and find a novel experimental and theoretic bases to develop an ideal sustained release system for water-soluble drugs.Methods The Cap/CGNPMs was manufactured by the methods of emulsification and cross-linking with natural and decomposed chitosan and getalin.In vitro evaluation for Cap/CGNPMs were carried out by optical and scanning electron microscopy and UV spectrometry.Results The results indicated that Cap/CGNPMs had a spherical shape,smooth surface morphology and integral inside structure and no adhesive phenomena and good mobility,and distributive margin was mainly from 220 to 280μm.Researches on the release of Cap from the microspheres in vitro demonstrated that Cap/CGNPMs was of the role of retarding release of Cap compared with Cap ordinary tablets (COT),embedding ratio (ER),drug loading (DL),swelling ratio (SR) and release behaviors of CGNPMs were influenced by process conditions of preparation such as experimental material ratio (EMR),composition of cross linked reagents.Among these factors,the EMR(1∶4),CLR(For+TPP) and 0.75% microcrystalline cellulose (MCC) added to the microspheres were the optimal scheme to the preparation of Cap/CGNPMs.Conclution The Cap/CGNPMs had a good characteristics of sustained release of drug and the process of emulsification and cross-linking process were simple and stable.The CGNPMs was probable to be one of a novel sustained release system for water-soluble drugs.