Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Sci Rep. 2020 Nov 4;10(1):19010. doi: 10.1038/s41598-020-75900-1.
Ethanol precipitation is an important separation and purification process in the traditional Chinese medicines (TCMs) industry. In the present study, a membrane dispersion micromixer was applied to achieve good mixing for the ethanol precipitation process of Astragali radix concentrate. New experimental apparatus was set up to rapidly lower the temperature of ethanol solution before mixing with the concentrate. Ethanol precipitation process was optimized according to Quality by design concept. To identify critical material attributes (CMAs), ten batches of Astragali radix were used to prepare concentrates. Calycosin-7-O-β-D-glucoside content, the sucrose content, and the electrical conductivity were found to be CMAs after the correlation analysis and stepwise regression modelling. Definitive screening design was used to investigate the relationships among critical process parameters, CMAs, and process critical quality attributes (CQAs). Quadratic models were developed and design space was calculated according to the probability of attaining process CQA standards. A material quality control strategy was proposed. High quality and low quality Astragali radix concentrates can be discriminated by the inequalities. Low quality Astragali radix concentrates should not be released for ethanol precipitation process directly. Verification experiment results indicated accurate models and reliable design space. The temperature control method and control strategy are promising for ethanol precipitation process of other TCMs or foods.
乙醇沉淀是中药（TCM）行业中重要的分离纯化过程。本研究采用膜分散微混合器实现了黄芪浓缩液乙醇沉淀过程的良好混合。为了在与浓缩液混合之前快速降低乙醇溶液的温度，建立了新的实验装置。根据质量源于设计的概念，对乙醇沉淀工艺进行了优化。为了确定关键物料属性（CMAs），使用十批黄芪制备了浓缩液。通过相关分析和逐步回归建模，发现毛蕊异黄酮-7-O-β-D-葡萄糖苷含量、蔗糖含量和电导率是 CMAs。采用确定性筛选设计研究了关键工艺参数、CMAs 和工艺关键质量属性（CQAs）之间的关系。根据达到工艺 CQA 标准的概率，建立了二次模型并计算了设计空间。提出了一种物料质量控制策略。不等式可区分高质量和低质量的黄芪浓缩液。低质量的黄芪浓缩液不应直接放行用于乙醇沉淀过程。验证实验结果表明模型准确，设计空间可靠。该温度控制方法和控制策略有望应用于其他 TCM 或食品的乙醇沉淀过程。
