Optimization of membrane dispersion ethanol precipitation process with a set of temperature control improved equipment.

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.