目的 研究二氧化硅固化感冒清热颗粒（Ganmao Qingre Granules，GQG）中挥发油成分的球磨法制备工艺，优化工艺参数。方法 建立二氧化硅固化GQG挥发油中薄荷酮、L-薄荷醇、胡薄荷酮的气相色谱（gas chromatography，GC）含量测定方法；以制成物的外观性状和薄荷酮、L-薄荷醇、胡薄荷酮的含量变化为评价指标，优选球磨罐材质；以薄荷酮、L-薄荷醇、胡薄荷酮的混合均匀度（relative standard deviatio，RSD）、吸附率及挥发率为评价指标，采用熵权法优选二氧化硅型号；采用Box-Behnken设计（Box-Behnken design，BBD）-响应面法（response surface methodology，RSM）结合熵权法优化制备工艺，确定球磨罐填充率、球磨机转速、油料比以及球磨时间等4个关键工艺参数（critical process parameters，CPPs），建立工艺设计空间并进行工艺验证。结果 建立的GC定测方法在线性、精密度、重复性、稳定性和加样回收等试验均符合检测要求；球磨罐材质可选用玛瑙或氧化锆；普通型二氧化硅吸附效果较好；4个关键工艺参数的设计空间为球磨罐填充率为64%～67%，球磨机转速为质反应因素，固定为400 r/min，油料比为1：1.1～1：1.2，球磨时间为54～60 min。结论 所建立的薄荷酮、L-薄荷醇、胡薄荷酮3种成分的GC测定方法能够满足检测要求，研究确定的二氧化硅固化GQG挥发油制备工艺可行。

Objective To study the ball milling process for preparing volatile oil components in silica solidified Ganmao Qingre Granules (感冒清热颗粒, GQG) and optimize process parameters. Methods A gas chromatography (GC) method for the determination of menthone, L-menthol and pulegone in the complex of silica solidified GQG volatile oil was established; Based on the appearance characteristics of the products and the changes in the content of menthone, L-menthol and pulegone, the ball milling tank material was selected; Using the relative standard deviatio (RSD), adsorption rate and volatilization rate of menthone, L-menthol and pulegone as evaluation indicators, the entropy weight method was used to select the optimal type of silica; Box-Behnken design (BBD)-response surface methodology (RSM) combined with entropy weight method were used to optimize the preparation process, four critical process parameters (CPPs) were determined, including ball milling tank filling rate, ball mill speed, oil material ratio and ball milling time. A process design space was established and process validation was conducted. Results The established GC assay method met the detection requirements in terms of linearity, precision, repeatability, stability and sample recovery; The material of the ball milling tank can be agate or zirconia; The adsorption effect of ordinary silica was better; The design space for the four critical process parameters was as follow:The filling rate of the ball milling tank was 64%-67%, the ball milling speed was a quality reaction factor, fixed at 400 r/min, the oil material ratio was 1:1.1-1:1.2, and the ball milling time was 54-60 min. Conclusion The established GC determination method for the three components of menthone, L-menthol and pulegone can meet the detection requirements, and the preparation process of silica solidified GQG volatile oil is feasible.

R283.6