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Optimization of alcohol precipitation process optimization of licorice based on the concept of quality by design
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DOI   10.11656/j.issn.1673-9043.2023.04.15
Key Words   quality by design;design space;licorice polysaccharide yield;glycyrrhizic acid encapsulation rate;encapsulation rate of liquiritin
Author NameAffiliationE-mail
LI Xiang College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
JING Yaoyao College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
LI Sheng College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
LI Chao College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
ZHANG Jie College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
DING Hui College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
YU Heshui 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 
 
SONG Xinbo 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 
songxinbo@tjutcm.edu.cn 
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 
 
Abstract
    [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.

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