苦参碱时控型结肠定位给药微丸的制备和体外释药研究

 目的 用流化床包衣技术制备苦参碱时控型结肠定位给药微丸。 方法 使用流化床包衣设备，首先在空白丸芯上采用溶液上药法制备苦参碱载药微丸，然后以羟丙甲纤维素（ HPMC ）和乙基纤维素水分散体（ Surelease ）的混合物包衣作为溶胀控释层，以 Surelease 包衣作为时控包衣层，制备时控型结肠定位给药微丸。分别用扫描电镜、溶出度测定和光学显微镜考察微丸的包衣质量、体外释药率和释放过程中微丸的变化。 结果 药物通过时控层破裂开始大量释放 , 调节该层增重和溶胀控释层的增重及此层中 HPMC 与 Surelease 比例，均可以调节释药时滞 , 控制药物的释放速度。优化后的包衣微丸在模拟胃肠道 pH 情况下延迟 5 h 释药，之后药物近恒速释放， 16 h 内药物释放完全。 结论 可通过调节时控层的增重 , 溶胀控释层的增重及此层中 HPMC 与 Surelease 比例来制备不同时滞的苦参碱时控型结肠定位给药微丸，为小分子水溶性药物制成时控型延迟释药微丸提供参考。

Preparation and <>in Vitro Characterization of Time-Controlled Matrine Pellets for Colonic Delivery

OBJECTIVE To prepare time-controlled matrine pellets by fluidized bed for colonic delivery. METHODS ■Firstly, the pellets containing the drug were prepared by fluidized bed coater. Then, pellets were coated with the mixture of HPMC and ethylcellulose aqueous dispersion (Surelease) as the swelling and controlled release layer. Subsequently, the outer layer of the pellet was coated with Surelease as the time-controlled film. The release rates of coated pellets were investigated by dissolution test in vitro. Coating quality and the changing process of coated pellets in the dissolution media were evaluated by scanning electron microscope (SEM) and optical microscope (OM), respectively. RESULTS The rapid release of matrine started by rupture of time-controlled layer. The thickness of two coating layers and the ratio of Surelease to HPMC could control the lag time of the coating pellets and the rate of release. In the optimized double-layer coated pellets, drug release was initiated after a lag time of 5 h and completed within 16 h by a nearly constant speed in a step changed pH media. CONCLUSION The thickness of two coating layers and the ratio of Surelease to HPMC could control the lag time of the coating pellets and the rate of drug release. The approach utilized in the present study may be helpful to formulate other hydrophilic drugs with low molecule weight for preparation of time-controlled pellets for colonic delivery or delayed release.