[Multivariate regulation study on critical spray-drying process of Gegen Qinlian Granules by coupling mixture design with Box-Behnken response surface methodology].

The spray-drying process of Gegen Qinlian Decoction(GQD) concentrate was optimized by coupling the mixture design with Box-Behnken response surface methodology. The aim is to quantify the contents of key active components such as puerarin and baicalin, significantly alleviate the formulation bottlenecks such as strong hygroscopicity and poor flowability of the spray-dried powder, and provide scientific theoretical support for the process in efficient preparation and quality improvement of granules of this classic prescription. The powder yield, hygroscopicity, and angle of repose of the GQD dried powder were used as core evaluation indicators to carry out the research on excipient screening. The mixture design method was employed to complete the optimization and screening of the optimal excipient ratio. Based on the above optimization results, a single-factor experiment was conducted, where the relative density of the feed solution, feed rate, and inlet air temperature were selected as key influencing factors, and the contents of puerarin, baicalin, berberine, and liquiritin, along with the spray-dried powder yield, were used as comprehensive evaluation indicators for overall scoring system construction. Finally, the Box-Behnken response surface methodology was used to further optimize and predict the spray drying process. The screening excipients were dextrin, maltodextrin, and lactose in a ratio of 0.225∶0.225∶0.05. The optimal spray drying process for GQD was determined to be a relative density of feed solution of 1.05(50 ℃), a feed rate of 15 r·min~(-1), and an inlet air temperature of 155 ℃. Under these conditions, the spray-dried powder yield was 78.93%, with an overall score of 84.19 points. The optimized excipients and their ratio could significantly improve the spray-drying yield. Under this process condition, the dried powder with low hygroscopicity and excellent flowability was obtained. The established spray-drying process is stable, feasible, and highly reproducible, providing solid theoretical evidence and technical support for research on the formation mechanism and large-scale industrial production of GQD granules.