基于质量源于设计理念优化甘草多糖醇沉工艺  

Optimization of alcohol precipitation process optimization of licorice based on the concept of quality by design

作　　者：李想 荆瑶瑶 李胜 李超 张杰 丁辉 余河水 宋新波 李正 LI Xiang;JING Yaoyao;LI Sheng;LI Chao;ZHANG Jie;DING Hui;YU Heshui;SONG Xinbo;LI Zheng(College of Pharmaceutical Engineering of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;State Key Laboratory of Co-construction of Component Traditional Chinese Medicine,Tianjin 301617,China;Municipal Experimental Teaching Demonstration Center of Traditional Chinese Medicine Pharmaceutical Engineering,Tianjin 301617,China)

机构地区：[1]天津中医药大学中药制药工程学院,天津301617 [2]组分中药国家重点实验室,天津301617 [3]中药制药工程市级实验教学示范中心,天津301617

出　　处：《天津中医药大学学报》2023年第4期491-497,共7页Journal of Tianjin University of Traditional Chinese Medicine

基　　金：天津市科技计划项目(20ZYJDJC00090)。

摘　　要：[目的]基于“质量源于设计”(quality by design,QbD)理念,采用设计空间法优化甘草多糖醇沉工艺。[方法]将甘草多糖得率、甘草酸包裹率、甘草苷包裹率3个指标作为关键质量属性(critical quality attributes,CQAs),利用多因素显著实验(Plackett-Burman Design,PBD)对醇料比、静置时间、搅拌时间、搅拌速度、加醇方式、加醇速度6个工艺参数进行设计,运用Box-Behnken设计实验建立了关键质量属性与关键工艺参数(critical process parameters,CPPs)的数学模型。最后运用Design Expert12.0构建甘草多糖醇沉工艺的设计空间,并通过蒙特卡罗法(Monte Carlo,MC)验证设计空间的准确度。[结果]通过PBD筛选出醇料比、搅拌时间、加醇速度3个CPPs,方差分析结果显示模型P值均小于0.05,失拟值均大于0.05,可以较好地描述CQAs和CPPs之间的关系,设计空间的准确度为99%~100%。[结论]研究基于QbD理念及设计空间法确定了醇沉工艺的最佳条件,有利于保证甘草多糖产品质量可控,为甘草多糖醇沉工艺优化提供指导。[Objective]Based on the concept of“quality by design”(QbD),the design space method was used to optimize the alcohol precipitation process of licorice polysaccharide.[Methods]The yield of glycyrrhizin,the encapsulation rate of glycyrrhizic acid,and the encapsulation rate of liquiritin were used as critical quality attributes(CQAs),and the Plackett-Burman Design(PBD)was used to compare the ratio of alcohol to material.Static time,mixing time,mixing speed,alcohol adding method,alcohol adding speed 6 process parameters are designed,using Box-Behnken design experiment to establish the mathematical model of CQAs and CPPs.Finally,the Design Expert 12.0 was used to construct the design space of the alcohol precipitation process of licorice polysaccharide,and the accuracy of the design space was verified by Monte Carlo(MC).[Results]Three critical process parameters(CPPs)of alcohol-to-feed ratio,stirring time,and alcohol addition speed were screened out by PBD.The results of variance analysis showed that the model P values were all less than 0.05,and the lack of fit values were all greater than 0.05,which can be compared.To describe the relationship between CQAs and CPPs well,the accuracy of the design space is 99%-100%.[Conclusion]This study determined the optimal conditions of the alcohol precipitation process based on the QbD concept and the design space method,which is beneficial to ensure the controllable quality of licorice polysaccharide products and provide guidance for the optimization of the alcohol precipitation process of licorice polysaccharides.

关 键 词：质量源于设计 设计空间 甘草多糖得率 甘草酸包裹率 甘草苷包裹率 

分 类 号：R284.2[医药卫生—中药学]