QbD理念的国医大师路志正名方研究:美颜舒气方提取工艺及颗粒成型工艺优化研究

Study on famous prescription of prestigious traditional Chinese medicine master Lu Zhizheng based on QbD concept: optimization of extraction process and granule forming process of Meiyan Shuqi Prescription

质量源于设计(quality by design,QbD)作为一种先进的国际制剂研究理念,能够完成药品质量从检验出来到设计出来的策略要求。该文基于质量源于设计理念建立美颜舒气方提取工艺的设计空间并优选其颗粒剂的成型工艺。以加水倍量、提取时间和提取次数为关键工艺参数(critical process parameters,CPPs),总黄酮的提取量为关键质量属性(critical quality attribute,CQA),采用Box-Behnken设计优化提取工艺,建立美颜舒气方提取工艺设计空间并进行验证。方差分析结果显示,二次项回归模型P<0. 01,表明所建模型具有统计学意义,各因素与响应值之间的关系可以用所建的模型进行函数化。进而通过模型预测,确定最佳提取工艺为13倍量水,提取3次,单次提取时间1. 4 h。进一步通过单因素考察优选出的成型工艺为:赋形剂为糊精,浸膏粉与辅料比例为1∶1,润湿剂为70%乙醇,润湿剂用量为0. 3 m L·g-1。该研究基于QbD理念开发的美颜舒气方提取工艺及其成型工艺为其他中药方剂的研究提供了参考。

Based on the concept of quality by design(QbD),the design space of Meiyan Shuqi Prescription extraction process was established,and its granules forming process was optimized.The content of total flavonoids was the critical quality attribute(CQA).The amount of water,extraction time and frequency were used as the critical process parameters(CPPs).Box-Behnken experimental design was used to optimize the extraction process.The design space of Meiyan Shuqi Prescription extraction process was established and verified.The results of variance analysis showed that the P value of the quadratic regression model was less than 0.01,which indicated that the model had a statistical significance,and the relationship between each factor and response value could be functionalized by the established model.Through further optimization of design space,the optimal extraction process of Meiyan Shuqi prescription was13-fold volume of water,extraction for 3 times and each extraction time of 1.4 hours.Furthermore,the forming process optimized by single factor was as follows:the excipient was dextrin;the ratio of extract powder to excipient was 1∶1;the wetting agent was 70%ethanol;and the amount of wetting agent was 0.3 m L·g-1.The Meiyan Shuqi Prescription extraction process and the forming process based on QbD concept provide reference for the study of other traditional Chinese medicine prescriptions.