盐酸地尔硫脉冲控释微丸的制备与体外释放影响因素的研究

STUDIES ON PREPARATION OF DILTIAZEM HYDROCHLORIDE PULSATILE CONTROLLED-RELEASE PELLETS AND VARIOUS INFLUENCE FACTORS

目的制备盐酸地尔硫牙脉冲控释微丸并考察体外释放影响因素。方法采用挤出滚圆法制备载药丸芯,以流化床包衣法分别包覆内层低取代羟丙基纤维素(low substituted hydroxypropylcellulose,L-HPC)溶胀层和外层乙基纤维素水分散体控释层来制备脉冲控释微丸,并考察溶胀层材料类型、溶胀层包衣增重、溶胀层包衣液中十二烷基硫酸钠(sodium alkyl sulfate,SDS)浓度及控释层包衣增重对释药的影响。结果药物通过控释层衣膜破裂而释放,溶胀层材料类型、溶胀层包衣增重、溶胀层包衣液中SDS浓度及控释层包衣增重等对脉冲控释微丸的释药时滞和释放速度均有显著影响。结论该方法制备的脉冲控释微丸,在模拟人体内胃肠道pH值变化条件下达到了时滞为4h,滞后1.5h,累积释药80%以上的脉冲释药效果。

Objective To study the preparation of dihiazem hydroehloride （DIL）pulsatile controlled- release pellets and various influence factors on in vitro release. Methods The cores of pulstile pellets were prepared by extrusion - spheronization and coated with low - substitued hydroxypropyleellulose （ L - HPC ） as the inner swelling layer and ethylcellulose aqueous dispersion as the outer controlled layer. The main factors including coating materials of the swelling layer, amount of swelling layer, concentration of sodium alkyl sulfate （ SDS ） in swelling layer, amount of outer controlled membrane, which influenced release of pellets, were investigated. Results The drug release was triggered by rupturing the membrane of the conrtolled layer. The coating materials of the swelling layer, amount of swelling layer, concentration of SDS in swelling layer, amount of outer controlled membrane had significant effect on the lag time and the release rate. Conclusion The pulstile release pellets, with a lag time of 4h and more than 80% released within following 1.5h under the simulated gastro intestinal pH conditons, can meet the requirements of pulstile release preparation.