【摘要】 以盐酸坦索罗辛为模型药物,将QbD理念应用于其缓释微丸的开发。采用挤出-滚圆法制备含药丸芯,以流化床对含药丸芯进行包衣,制备肠溶缓释微丸。对参比制剂深入研究后确认产品的关键质量属性为pH1.2介质中2h的释放度及换成pH7.2介质后继续溶出1h、3h的累积释放度。风险评估结果显示,对关键质量属性具有较高风险的因素为:丸芯中Eurdragit~NE30D的量(X1)、衣膜中Eudragit~L30D-55的比例(X2)、包衣增重(X3)。采用星点设计-效应面法对高风险因素进行效应分析,确定设计空间为X1:18.8%~21.0%,X2:15.0%~20.2%,X3:4.3%~6.1%,设计空间内产品符合预期且质量可控。更多还原

【Abstract】 Tamsulosin hydrochloride was used as the model drug to apply the quality by design theory in preparing sustained-release pellets. The drug-containing cores were prepared by extrusion-spheronization,and then the cores were coated with a fluidized bed to form the enteric-coated sustained-release pellets.After the reference was deeply analyzed, the critical quality attributes were determined as the drug release in pH 1.2 for 2 h and the accumulative release after the pallets were transferred to pH 7.2 buffer for 1 h and 3 h. According to the risk assessment, the most significant risk factors were determined as the percentage of Eurdragit~ NE30 D in the core(X1), the percentage of Eudragit~L30 D-55 in the coating membranes(X2) and the coating weight gain(X3). The central composite design-response surface method was chosen to describe the relationship between the high risk factors and the critical quality attributes.From the response surface, the design space of the risk factors was confirmed as: X1 at 18.8%-21.0%, X2 at 15.0%-20.2% and X3 at 4.3%-6.1%. With the above space, the quality-controlled products that meet the expectation were got.更多还原