Objective To optimize the extraction and β-cyclodextrin (β-CD) inclusion process for the volatile oil from the classical formula Dihuang Yinzi (地黄饮子) based on the quality by design (QbD) concept and the analytic hierarchy process-entropy weight (AHP-entropy) method. Methods Failure mode and effects analysis (FMEA) was employed for risk identification in the volatile oil extraction process. Heating time, material-to-liquid ratio, and soaking time were determined as the critical process parameters (CPPs), while cinnamaldehyde content, β-asarone content, and volatile oil extraction yield were defined as the critical quality attributes (CQAs). On the basis of single-factor tests, the Box-Behnken design-response surface methodology (BBD-RSM) was used for process optimization. The AHP-entropy weight method was applied to calculate a comprehensive score for the CQAs, which was then used to establish and validate an optimized design space. The inclusion process of volatile oil was investigated using the saturated aqueous solution method. The inclusion conditions were comprehensively optimized through orthogonal experimental design combined with the AHP-entropy weight method for multi-index evaluation. Finally, the optimal inclusion process parameters were determined and validated. Results The optimized volatile oil extraction process was as follows: soaking for 30 to 45 min, adding 9- to 10-fold volume of water, and extracting for 3.0 to 3.5 h. The optimal inclusion process parameters were: inclusion time of 2.0 h, β-cyclodextrin to volatile oil ratio of 10:1, and inclusion temperature of 30 ℃. Conclusion The volatile oil extraction and inclusion processes optimized based on the QbD concept and the AHP-entropy weight method can reliably ensure a stable extraction yield and consistent content of key active components. The resulting inclusion complex exhibits excellent quality. This study provides reliable data support and a solid process foundation for the industrial production and development of related Chinese medicinal preparations, while also offering a feasible pathway for the modern dosage form development of classical formulas.

quality by design (QbD)  /  AHP-entropy weight method  /  Dihuang Yinzi  /  volatile oil  /  inclusion  /  cinnamaldehyde  /  β-asarone