卡托普利生物粘附型缓释胶囊的制备及性能

为改善卡托普利治疗效果、降低其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,采用乳化分散法制备卡托普利/壳聚糖明胶网络多聚物微球,湿法制粒制备Cap生物粘附型缓释胶囊,研究结果表明,Cap生物粘附型缓释胶囊具有良好的胃肠道粘附特性、对胃肠道粘膜的粘附力与处方中羟丙基甲基纤维素(HPMC)用量呈正相关,而与碳酸钙和碳酸镁的用量呈负相关.体外释药试验证明,Cap生物粘附型缓释胶囊与Cap普通片相比具有明显延缓Cap释放作用,药物释放速率与HPMC用量呈负相关,释放动力学模拟结果表明其体外释药行为以希古切(Higuchi)为最佳拟合模型,结果说明,Cap生物粘附型缓释胶囊药物释放行为是扩散和骨架溶蚀协同作用的结果。

Preparation and Evaluation in Vitro for Captopril/Bioadhesive Sustained-Release Capsules

To improve the therapeutic efficiency, decrease the side effects of captopril(Cap), and find a novel experimental and theoretic basis for the development of an ideal sustained release system for water-soluble drugs, the Cap/chitosan-gelatin microspheres were pcepared by emulsification and cross-linking with chitosan and gelatin, and the captopril/bioadhesive sustained-release capsules (Cap/BSRCs) were prepared by the method of wet granulation. The results indicated that the Cap/BSRCs had adhesive characteristics on gastrointestinal mucosa in vitro. The adhesive force of Cap/BSRCs to gastrointestinal mucosa was positively correlated with the content of hydroxypropyl methyl cellulose (HPMC), negatively correlated with the content of the fillers such as calcium carbonate and magnesium carbonate. The drug release experiment in vitro confirmed that the Cap/BSRCs had sustained-release behavior compared with Cap ordinary tablets (COT) and the release velocity of Cap was positively correlated with the content of HPMC. The dissolution curve in vitro of Cap from Cap/BSRCs showed that the drug release could be best described by the Higuchi equation, which suggested that the release profiles of Cap from Cap/BSRCs were the result of diffusion comkined with bulk erosion.