数字中医药（英文）2022，Vol.5Issue(2)：189-198,10.DOI:10.1016/j.dcmed.2022.06.008
基于质量源于设计(QbD)理念的喘贴灵提取工艺研究
Extraction process in Chuantieling (CTL) based on the quality by design (QbD) concept
摘要
Abstract
Objective This study aimed to design and optimize the water extraction process for Chuantieling (喘贴灵, CTL) based on the concept of quality by design (QbD). Methods The single-factor experiments were used to select the best experimental points of CTL water extraction. On this basis, the transfer rate of ephedrine hydrochloride and sin-apine thiocyanate, and the yield of the extract were evaluated as the evaluation indicators. The liquid-solid ratio, extraction time, and pH value were selected as the main factors to carry out the Box-Behnken design (BBD). A mathematical model of the critical process parameters (CPPs) and critical quality attributes (CQAs) was established, the interaction between CQAs and CPPs was examined, and the CTL extraction process design space was established and optimized, which guaranteed the stability of the process. The high performance liquid chro-matography (HPLC) was used to analyze the main active compounds in the CTL extract. Results Through single-factor experiments, the best experimental parameters were found to be a liquid-solid ratio of 8:1, extraction time of 90 min, pH value of 4, and extraction times of three. The experimental variance analysis results of the BBD showed that the P value of the re-gression model was less than 0.05, and the lack-of-fit value was greater than 0.01, indicating that the constructed model had good predictive ability. The operating space of the CPPs of the CTL water extraction process was combined with the actual production situation. In the pro-duction situation, the best extraction process was nine times of water addition, 72 min of ex-traction time, and 4.5 of pH value. The HPLC results showed that the peak areas of ephedrine hydrochloride, sinapine thiocyanate, tetrahydropalmatine, methyl eugenol, cinnamaldehyde, and 6-gingerol in the CTL extract accounted for 0.94％, 14.32％, 0.78％, 31.23％, 0.34％, and 0.44％ of the total peak area, respectively. Conclusion The water extraction process design space of CTL based on QbD was conducive to actual production operations, ensuring the stability of the process.关键词
喘贴灵/质量源于设计/Box-Behnken设计/关键质量属性/关键工艺参数/麻黄/芥子/盐酸麻黄碱/芥子硫氰酸盐Key words
Chuantieling (CTL)/Quality by design (QbD)/Box-Behnken design (BBD)/Critical quality attributes (CQAs)/Critical process parameters (CPPs)/Mahuang (Ephedrae Herba)/Jiezi (Sinapis Semen)/Ephedrine hydrochloride/Sinapine thiocyanate引用本文复制引用
李雅,李姿锐,郭志华..基于质量源于设计(QbD)理念的喘贴灵提取工艺研究[J].数字中医药（英文）,2022,5(2):189-198,10.基金项目
Hunan University of Traditional Chinese Medicine Graduate Training Quality Engineering Project(2019CX57),and the First-class Discipline Project on Chinese Pharmacology of Hunan University of Chinese Medicine(201803). （2019CX57）
