环丙沙星/壳聚糖植入微球的制备及其体外释放研究

Preparation and in vitro release of CPX/CMC implantable sustained-release microspheres

目的 :探讨制备植入微球的工艺、确定调控微球缓释速率的途径。 方法 :以水溶性羧甲基壳聚糖 (CMC)作为缓释辅料 ,以环丙沙星 (CPX)为模型药物通过乳化交联工艺制备 CPX/CMC微球 ;应用扫描电镜等方法考察其理化特性 ;建立持续流动释放系统 ,检测微球的体外释放特性和影响因素。 结果 :微球的理化特性受工艺条件如温度、离子强度、载药量比例量等因素影响 ;CPX体外释放行为符合 H iguchi方程 ,微球的体外释放速率与微球交联度、粒径呈负相关 ,与载药量呈正相关 ,与酶的降解无关。结论 :CMC可作为缓释微球辅料 ;乳化交联的制备工艺简单且稳定 ;微球的释放速率可控。CMC微球是一种良好的药物缓释载体。

Objective: To study the preparation process, release characteristics and influencing factors of CPX/CMC implantable sustained release microspheres prepared with water soluble carboxymethyl chitosan (CMC,a new adjuvant). Methods: CPX/CMC microspheres were achieved by emulsification and cross linking process; Physical and chemical characteristics of microspheres were detected using scanning electron microscopy(SEM) and other methods. A continual flowing system was used to determine the releasing characteristic of microspheres in vitro and its influencing factors, then the way to modulate the release rate was found. Results: The physical and chemical characteristics of microspheres were influenced by process conditions such as: temperature, ionic strength, the drug content and so on. Its release behavior conformed to Higuchi model. Release rate was negatively correlated with cross linking extent and granule diameter, positively correlated with the drug contents, but was independent of degradation of lysozyme. Conclusion: It is feasiable to prepare sustained release microspheres with CMC, and emulsification cross linking process is simple and stable. The release rate of drug from microspheres is adjustable.