基于确定性筛选设计优化榆皇生肌乳膏的制备工艺  

Optimization of the preparation process of Yuhuang Shengji Cream based on definitive screening design

作　　者：钱喜龙 王可为[4] 刘政 周柳 马瑜璐 房方[1,2] 章阳 王业皇[4] 江滨[4] 刘圣金[1,2,3] QIAN Xi-long;WANG Ke-wei;LIU Zheng;ZHOU Liu;MA Yu-lu;FANG Fang;ZHANG Yang;WANG Ye-huang;JIANG Bin;LIU Sheng-jin(State National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture,Jiangsu Kanion Pharmaceutical Co.,Ltd.&Nanjing University of Chinese Medicine,Nanjing 210000,China;School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,Nanjing 210023,China;Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,Nanjing 210022,China)

机构地区：[1]中药制药过程控制与智能制造技术全国重点实验室/江苏康缘药业股份有限公司/南京中医药大学,南京210000 [2]南京中医药大学药学院,南京210023 [3]江苏省中药资源产业化过程协同创新中心,南京210023 [4]南京中医药大学附属南京中医院,南京210022

出　　处：《中国新药杂志》2024年第23期2518-2528,共11页Chinese Journal of New Drugs

基　　金：江苏省高等学校基础科学(自然科学)研究重大项目(24KJA36006);国家中医药管理局高水平中医药重点学科建设项目-中药资源化学(zyyzdxk-2023083);教育部科技委员会矿物中药现代化战略研究项目(2021);江苏省中医药科技发展计划项目(MS2023051);第二批江苏省名老中医药专家传承工作室建设项目(20201001);南京市中医药青年人才培养计划(ZYQ20042)。

摘　　要：目的:在确定性筛选设计的帮助下,系统地研究关键工艺参数,优化榆皇生肌乳膏的制备工艺。方法:依据确定性筛选设计来设计一系列实验,并使用旋转流变仪测试乳膏的流变特性,以获得关键的流变数据。通过对实验数据进行逐步回归拟合分析,探索因子与响应之间的复杂关系。基于这些实验数据进行模拟实验,并利用决策树来确定最合适的因子取值范围,以提高制备工艺的稳定性。应用高斯过程优化方法,在预设范围内寻找最优的参数配置,进一步优化榆皇生肌乳膏的制备工艺。结果:经过优化得到的工艺范围:乳化温度(85±5.5)℃、混合转速(432±51)×g、药物比例(20±2)%、硬脂醇(14.1±1)g、白凡士林(30±2)g、十二烷基硫酸钠(1±0.16)g,在小范围内的波动不会对乳膏产生较大影响。最佳工艺为药物比例20%、乳化温度85℃、混合转速432×g、硬脂醇14 g、白凡士林30 g、十二烷基硫酸钠1 g。在此条件下乳膏生产发生缺陷的概率为0.04329。结论:确定性筛选设计方法可以有效地优化榆皇生肌乳膏的制备工艺,同时该方法为其他中药复方的乳膏制备工艺优化提供了参考。Objective:With the help of definitive screening design,the key process parameters were systematically optimized for the preparation process of Yuhuang Shengji Cream.Methods:A series of experiments were designed according to the definitive screening design,and the rheological properties of the cream were tested with a rotary rheometer to obtain the key rheological data.The complex relationship between factors and responses was explored by stepwise regression analysis of experimental data,based on which the simulation experiment was carried out,and the decision tree was used to determine the most appropriate range of factors to improve the stability of the preparation process.The Gauss process optimization method was applied to find the optimal parameter configuration in the preset range to further optimize the preparation process of Yuhuang Shengji cream.Results:The optimal process range obtained by optimization is as follows:emulsification temperature at(85±5.5)℃,mixing speed at(432±51)×g,drug proportion of(20±2)%,stearyl alcohol(14.1±1)g,white vaseline(30±2)g,and sodium dodecyl sulfate(1±0.16)g.The fluctuation in a small range did not have a great impact on the cream.The optimal process was as follows:drug proportion of 20%,emulsification temperature at 85℃,mixing speed at 432×g,stearyl alcohol 14 g,white vaseline 30 g,and sodium dodecyl sulfate 1 g.Under this condition,the probability of defect in cream production is 0.04329.Conclusion:The preparation process of Yuhuang Shengji cream was effectively optimized using the definitive screening design method.This method provides a reference for the preparation process optimization of other traditional Chinese medicine compound creams.

关 键 词：临床经验方 含矿物药中药复方 乳膏 制备工艺 确定性筛选设计 流变学 机器学习 

分 类 号：R943[医药卫生—药剂学]