Objective  Based on the quality of Folium stevia standard decoction, to establish a design space for the extraction process of Folium stevia formula granules.

Methods  15 batches of Folium stevia standard decoction were prepared, and the paste rate, the extraction amount of steviol glycoside, as well as the total extraction amount of neochlorogenic acid, chlorogenic acid and cryptochlorogenic acid were measured. The comprehensive score of standard decoction were calculated using the analytic hierarchy process-entropy weighting method to determine weight coefficients of each indicator. Using comprehensive evaluation as key quality attribute and soaking time, extraction time, water addition ratio as key process parameters, the Box-Behnken design was used to optimize the extraction process of Folium stevia formula granules and the design space was established. Meanwhile, the accuracy of the model, process stability, and process applicability were validated.

Results  The comprehensive score range for 15 batches of Folium Stevia standard decoction was 56.77-98.30, with an average value of 78.03. The extraction design space for the established Folium Stevia formula granules was as follows: the soaking time was 10-30 min, the water addition ratio was 11-12 times, and the extraction time was 45-55 min. The comprehensive scores of three validation points were 85.24, 85.19 and 88.25, and the repeatability of same validation point was good. The different batches of Folium stevia decoction pieces were extracted using process parameters within the designed space, and the comprehensive score was also significantly improved.

Conclusion  The established design space can ensure the stability of Folium stevia extraction process and provide reference ideas for preparing formula granules that were consistent with standard decoction.

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