Ding Rui-Xue, He Yan, Tian Xiang, Cai Da-Yu, Yang Xiao-Mei, Rao Xiao-Yong, Luo Xiao-Jian
Jiangxi University of Traditional Chinese Medicine Nanchang 330004,China.
Chutian Technology Company Limited Ningxiang 410600,China.
Zhongguo Zhong Yao Za Zhi. 2019 Jul;44(13):2799-2805. doi: 10.19540/j.cnki.cjcmm.20190410.302.
To establish and validate the design space of the Digeda-4 flavored decoction( DGD-4D) extraction process by using the quality by design( Qb D) concept. With DGD-4D decoction pieces as a model drug,with the transfer rate of aesculin,picroside I,picroside Ⅱ,geniposide and the yield of extract as critical quality attributes( CQAs),the single factor experiment design was used to determine the level of each factor; the Plackett-Burman experiment design was used to select the critical process parameters( CPPs);and the Box-Behnken experiment design was used to optimize the extraction process. The design space of the DGD-4D extraction process was established,and finally,four experimental points were selected to verify the established model. The single factor experiment determined the levels of each factor,including soaking time 60 min and 30 min,water adding volume 12 times and 8 times,extraction time 90 min and 30 min,number of extraction times 3 times and 1 time,as well as extraction temperature 100 ℃ and 90 ℃.By Plackett-Burman experimental design,the DGD-4D water addition,extraction time and number of extraction times were determined to be CPPs. The Box-Behnken experimental variance analysis showed that P of the regression model was less than 0. 01 and the misstated value was more than 0. 01,indicating that the model had good predictive ability,and the operation space of CPPs in the DGD-4D extraction process was determined as follows: the amount of water addition was 10-12 times; extraction time 50-80 min; and number of extraction times was 3 times. The design space of DGD-4D extraction process based on the concept of Qb D is conducive to improving the stability of product quality and laying a foundation for the future development of DGD-4D.
采用质量源于设计（QbD）理念建立并验证地革达-4味汤（DGD-4D）提取工艺的设计空间。以DGD-4D饮片为模型药物，以秦皮苷、栀子苷Ⅰ、栀子苷Ⅱ、京尼平苷的转移率和提取物得率为关键质量属性（CQAs），采用单因素试验设计确定各因素水平；采用Plackett-Burman试验设计筛选关键工艺参数（CPPs）；采用Box-Behnken试验设计优化提取工艺。建立了DGD-4D提取工艺的设计空间，最后选取4个试验点对所建立的模型进行验证。单因素试验确定了各因素水平，包括浸泡时间60 min和30 min、加水量12倍和8倍、提取时间90 min和30 min、提取次数3次和1次以及提取温度100℃和90℃。通过Plackett-Burman试验设计，确定DGD-4D的加水量、提取时间和提取次数为CPPs。Box-Behnken试验方差分析表明，回归模型的P值小于0.01，失拟值大于0.01，表明模型具有良好的预测能力，确定DGD-4D提取工艺中CPPs的操作空间如下：加水量为10～12倍；提取时间50～80 min；提取次数为3次。基于QbD理念的DGD-4D提取工艺设计空间有利于提高产品质量稳定性，为DGD-4D的未来开发奠定基础。
