5-氨基水杨酸时控结肠定位控释微丸及其制剂的研制

目的制备5-氨基水杨酸微丸及其时控结肠定位控释释药系统的研究。方法首先采用挤出滚圆机制备了含药微丸,然后使用流化床包衣设备将微丸包衣,以羟丙甲纤维素和微粉硅胶的混合物包衣作为溶胀控释层,以乙基纤维素水分散体Surelease包衣作为时滞包衣层,并将包衣微丸装入肠溶胶囊。用释放度测定法研究微丸的释放行为。结果药物通过时滞层破裂开始释放,该层厚度增加可显著延长释药时滞。调节羟丙甲纤维素的型号、包衣增重及羟丙甲纤维素与微粉硅胶两者比例,可以控制药物释放速度。在模拟胃肠道pH情况下延迟5 h释药,之后的10 h内释药完全。结论可通过调整溶胀控释层包衣混合物的比例、型号、包衣厚度及时滞层的包衣厚度,制备5-氨基水杨酸时控结肠定位控释释药系统。

Preparation of time-controlled 5-ASA controlled-release colon-specific pellets and its preparations

Abstract: Objective　To prepare time-controlled 5-aminosalicylic acid (5-ASA) controlled-release colon-specific pellets and drug delivery system. Methods　Firstly, the pellets containing the drug were prepared by extrusion spheronizer, then the pellets were coated with the mixture of HPMC and Aerosil as the swelling and control-releasing layer, subsequently, the outer layer of the pellets was coated with ethylcellulose aqueous dispersion- Surelease as the time controlled film. The film coating operation was performed using fluid-bed coater, then the coated pellets were encapsulated with enteric capsules, and the in vitro release profile was investigated in different pH media and step changed pH media for simulating gastrointestinal liquid. Results 　Steady drug release was triggered by rupturing the outer membrane, and the lag time was prolonged significantly with the increase of the thickness of the outer membrane. The drug release was controlled by the type of HPMC, film thickness, and the ratio of HPMC and Aerosil. The drug release was initiated after a lag time of 5 h and was completed within the following 10 h. Conclusions　The time-dependent pellets for 5-ASA controlled-release colon-specific delivery could be prepared by designing the inner swelling layer (HPMC type and ratio of the mixture) for control-releasing and outer EC film thickness for time-dependent.