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基于质量源于设计(Qb D)的理念,采用尤特奇~?丙烯酸树脂和流化床底喷包衣工艺制备艾司奥美拉唑镁肠溶微丸。根据研发生产经验和科学知识进行风险评估,确定以微丸收率和药物释放度作为关键质量属性(CQAs),以进风风量、物料温度、喷液速度和雾化压力为关键工艺参数(CPPs),以均匀设计方法安排试验,获得关联CQAs与CPPs的2个二次响应面回归模型,回归方程相关系数平方和分别为0.999 7和1.000 0,模型方差分析的P值均小于0.05。在设定的95%置信区间,建立了应用尤特奇~?丙烯酸树脂实施肠溶微丸包衣工艺的上述4个参数的设计空间。验证结果表明,在该设计空间内实施微丸包衣,可以保证产品的质量,降低产品质量风险,提高工艺过程的稳健性和灵活性。
Based on the QbD concept of quality, esomeprazole magnesium enteric-coated pellets were prepared using a Utica® acrylic resin and a fluidized bed bottom spray coating process. According to the R & D and production experience and scientific knowledge, risk assessment was carried out to determine the pellets yield and drug release as the key quality attributes (CQAs), air intake air volume, material temperature, spray speed and atomization pressure were the key process parameters ). The two quadratic response surface regression models of correlation CQAs and CPPs were obtained. The correlation coefficients of the regression equation were 0.999 7 and 1.000 0, respectively. The P values of the model ANOVA were all less than 0.05. In the set 95% confidence interval, the design space of the above four parameters for applying the enteric pellet coating process with Eudache® acrylic resin was established. Verification results show that the implementation of micro-pellet coating in this design space can ensure the quality of products, reduce product quality risks and improve the robustness and flexibility of the process.