张东阁 王凤霞 杨宇杰 王春民 陈宝鑫 吴鑫宇

中圖分类号 R944.2;R284.2 文献标志码 A 文章编号 1001-0408（2021）14-1734-07

DOI 10.6039/j.issn.1001-0408.2021.14.12

摘 要 目的： 优化感冒清热颗粒挥发油包合工艺。方法：以“质量源于设计”理念为指导，以挥发油包合率、包合物收得率为关键质量属性，两者加权后的综合评分为响应值，包合温度、包合时间、β-环糊精（β-CD）与挥发油比例为关键工艺参数，采用Box-Burman响应曲面设计建立关键工艺参数与关键质量属性的设计空间，通过95%置信区间优化设计空间并进行验证;同时初步考察了包合物的稳定性。结果：所得最优设计空间即最优工艺参数范围为包合温度35～40 ℃，包合时间1.8～2.0 h，β-CD与挥发油比例 9.5 ∶ 1～10 ∶ 1（g/mL）。3次验证实验结果显示，挥发油包合率均大于62%，包合物收得率均大于75%，综合得分均大于80分。初步稳定性结果显示，挥发油包合率、包合物收得率以及综合评分均未发生明显变化，7 d之内各项指标差异均在5%以内。结论：所得最优包合工艺可行，所得包合物稳定性良好。

关键词 质量源于设计理念;感冒清热颗粒;挥发油;包合工艺;Box-Burman响应曲面法;设计空间;稳定性

Optimization of Inclusion Technology of Volatile Oil from Ganmao Qingre Granules

ZHANG Dongge1，2，WANG Fengxia2，YANG Yujie1，WANG Chunmin2，CHEN Baoxin2，WU Xinyu2（1. Institute of TCM， Chengde Medical College， Hebei Chengde 067000， China; 2. Hebei Technology Innovation Center of TCM New Excipient Engineering， Jingfukang Pharmaceutical Group Co.， Ltd.， Hebei Chengde 067000， China）

ABSTRACT   OBJECTIVE： To optimize the inclusion technology of volatile oil from Ganmao qingre granules. METHODS： Guided by the concept of “quality by design”， taking volatile oil inclusion rate and inclusion complex yield as key quality attribute， comprehensive score of above two indexes after weighting as response value， inclusion temperature， inclusion time， the ratio of β-CD to volatile oil as key technology parameters， Box-Burman response surface design was adopted to establish the design space of key technology parameters and key quality attributes. The design space was optimized and verified by 95% confidence interval. The stability of inclusion complex was investigated preliminarily. RESULTS： The optimal design space， i. e. the optimal technology parameters rang， included inclusion temperature 35-40 ℃， inclusion time 1.8-2.0 h， the ratio of β-CD to volatile oil 9.5 ∶ 1- 10 ∶ 1 （g/mL）. The results of 3 validation tests showed that the volatile oil inclusion rates were all over 62%， the yields of inclusion complex were all over 75%， and the comprehensive scores were all over 80 point. The results of preliminary stability showed that the inclusion rate of volatile oil， the yield of inclusion complex and the comprehensive score did not change significantly. The difference in evaluation indicators within 7 days was within 5%. CONCLUSIONS： The optimized inclusion technology is feasible， and the obtained inclusion complex is stable.

KEYWORDS   Quality by design; Ganmao qingre granules; Volatile oil; Inclusion technology; Box-Burman response surface methodology; Design space; Stability

感冒清热颗粒是国家基本药物，具有疏风散寒、解表清热之功效[1-2]。该药由荆芥穗、薄荷、防风、柴胡、紫苏叶、葛根、苦杏仁、桔梗、白芷、苦地丁、芦根等11味药材组成，主治风寒感冒、头痛发热、咳嗽咽干等症[3]。感冒清热颗粒的化学成分复杂且种类较多，主要包括挥发油、苷元及水溶性成分[4]。其中，挥发油成分来源于荆芥穗、薄荷、紫苏叶等3味药材，相关研究结果表明，挥发油是感冒清热颗粒的主要药效部位，如荆芥穗挥发油可抑制或直接杀灭病毒，薄荷挥发油具有抗炎、镇痛、解热等药理活性，紫苏叶挥发油具有抑菌、提高免疫力等作用[5-8]。……