Multi-index optimization of alcohol extraction and water precipitation processes of Shenmai Injection based on quality by design concept / 中草药

ABSTRACT

Objective: The alcohol extraction and water precipitation processes of Shenmai Injection were optimized based on quality by design (QbD) concept and satisfaction algorithm. Methods: Hazard and operational analysis method was applied to conduct risk assessment of various process parameters in alcohol extraction and water precipitation processes of Shenmai Injection. Ethanol concentration, extraction time and alcohol-material ratio were selected as the critical process parameters of alcohol extraction, and the material pH, temperature and time were selected as the critical process parameters of water precipitation. A multiple linear regression model of critical process parameters and critical quality attributes were established by using Box-Behnken design. A design space was delineated according to the level of each index. Finally, the optimum operating condition was determined by the multi-index optimization algorithm. Results: Within the scope of the design space, when the alcohol concentration was 89.0%, the extraction time was 110 min, the alcohol-material ratio was 2.99, the desirability function of alcohol extraction of 0.722 was the best. When the material pH was about 4, the time was 40 h, the temperature was 2.0 ℃, the desirability function of water precipitation of 0.995 was the best. When the material pH was about 5, the time was 35 h, the temperature was 2.0 ℃, the desirability function of water precipitation of 0.999 was the best. Conclusion: The optimal conditions were determined based on QbD and satisfaction algorithm were conducive to ensuring the product quality and reducing the cost of production. This study has reference value for the guidance of pharmaceutical process research and actual industrial production.