基于QbD理念对蜡骨架缓释片的优化

Optimization of wax matrix sustained release tablets based on QBD

目的基于质量源于设计(quality by design,QbD)理念,剖析对照药的处方组成及关键工艺参数(CPPs),运用星点设计-效应面法优化蜡骨架缓释片的处方。方法以氯化钾为模型药物,运用失败模式和影响分析法(failure mode and effect analysis,FMEA)进行风险评估,确定CPPs,并采用星点设计-效应面法对CPPs进行优化,建立统计模型,得到最优的处方工艺。结果基于QbD理念,通过星点设计-效应面法对CPPs进行优化,以粉衣层明胶比例、粉衣层增重、隔离层层数、糖衣层增重为自变量,以0.25、0.5、1、2、4、6和8 h的累积释放百分率为因变量,绘制优化模型的效应面图,最终得到了最优的包衣工艺。建立了CPPs与CQAs的关联,并对最优包衣工艺进行验证,释放结果与预测值基本一致,自制片与参比制剂的体外释放行为一致。结论基于QbD理念,得到了优化模型的产品,符合预期的QTPP且质量稳定、可控。

Objective Based on the quality by design(QbD) concept and method,the prescription composition and key process parameters(CPPs) of the reference drug were dissected,and the prescription of the wax skeleton sustained-release tablet was optimized by the star point design-effect surface method.Methods Taking potassium chloride as a model drug,using failure mode and effect analysis(FMEA) for risk assessment,and using star point design-effect surface method to optimize key process parameters(CPPs) and establish statistical models,get the best prescription process.Results Based on the QbD concept,through the star design-response surface method to optimize the coating process,with proportion of gelatin,powder coat layer powder weight,the number of isolation layer upon layer,the sugar coating layer weight as independent variables,with 0.25,0.5,1,2,4,6 and 8 h cumulative release percentage as dependent variable,draw the optimization model of the effect of surface figure,finally gets the optimal coating process,the association established the CPPs with CQAs,and the optimal coating process verification,release the results and forecast,since the production is consistent with the reference preparations in vitro release behavior.Conclusion Based on the QbD concept,the product with optimized model is in line with the expected QTPP and the quality is stable and controllable.