目的 基于质量源于设计（quality by design，QbD）理念和层级分析法（analytical hierarchy process，AHP）-熵权法优化经典名方地黄饮子挥发油的提取与β-环糊精（β-cyclodextrin，β-CD）包合工艺。方法 运用失效模式与效应分析对挥发油提取过程进行风险辨识，确定加热时间、料液比及浸泡时间为关键工艺参数（critical process parameters，CPPs），以桂皮醛含量、β-细辛醚含量及挥发油提取率为关键质量属性（critical quality attributes，CQAs）。在单因素试验基础上，采用Box-Behnken设计-响应面法（Box-Behnken design-response surface methodology，BBD-RSM）进行工艺优化，结合AHP-熵权法计算各CQAs的综合评分，建立优化设计空间并完成验证。采用饱和水溶液法研究挥发油包合工艺，通过正交法结合AHP-熵权法对包合条件进行多指标综合优化，最终确定最佳包合工艺参数并进行验证。结果 优化所得挥发油的最佳提取工艺为浸泡30～45 min，加水量为9～10倍，提取3.0～3.5 h。挥发油的最佳包合工艺为包合时间2.0 h、β-CD与挥发油比例10∶1、包合温度30 ℃。结论 基于QbD理念与AHP-熵权法优化的挥发油提取与包合工艺，可稳定保障挥发油提取率及关键有效成分含量，且所获包合物质量优良，为相关中药制剂的工业化生产与研发提供了可靠的数据支撑与工艺基础，同时为经典名方的现代制剂开发提供了可行路径。

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.

R283.6

国家自然科学基金项目（82274388）；国家自然科学基金项目（82574905）；国家中医药管理局科技项目（GZY-KJS-2025-110）