基于设计空间法优化通便凝胶贴剂的提取工艺
投稿时间:2023-02-27     点此下载全文
引用本文:陈程,李小宁,李伟泽,赵宁,马远涛,李健,杨洁.基于设计空间法优化通便凝胶贴剂的提取工艺[J].中国现代中药,2023,25(12):2598-2605
DOI:10.13313/j.issn.1673-4890.20230227002
摘要点击次数: 81
全文下载次数: 0
                    
作者中文名作者英文名单位中文名单位英文名E-Mail
陈程* CHEN Cheng 西安医学院 药学院,陕西 西安 710021 School of Pharmacy, Xi'an Medical University, Xi'an 710021, China  
李小宁 LI Xiao-ning 陕西省药品和疫苗检查中心,陕西 西安 710065 Shaanxi Drug and Vaccine Inspection Center, Xi'an 710065, China  
李伟泽 LI Wei-ze 西安医学院 药学院,陕西 西安 710021
江苏微纳医药科技有限公司,江苏 扬中 212218
School of Pharmacy, Xi'an Medical University, Xi'an 710021, China
Jiangsu Weina Pharmaceutical Technology Co., Ltd., Yangzhong 212218, China
 
赵宁 ZHAO Ning 西安医学院 药学院,陕西 西安 710021 School of Pharmacy, Xi'an Medical University, Xi'an 710021, China  
马远涛 MA Yuan-tao 西安医学院 药学院,陕西 西安 710021 School of Pharmacy, Xi'an Medical University, Xi'an 710021, China  
李健 LI Jian 西安医学院 药学院,陕西 西安 710021 School of Pharmacy, Xi'an Medical University, Xi'an 710021, China  
杨洁 YANG Jie 西安医学院 药学院,陕西 西安 710021 School of Pharmacy, Xi'an Medical University, Xi'an 710021, China  
基金项目:2022年度陕西高校青年创新团队科研计划项目(22JP075);陕西省科技厅科技计划项目青年项目(2023-JC-QN-0822);陕西高校青年创新团队建设项目(陕教〔2019〕90号);西安医学院科技创新团队配套项目(2021TDPT04);西安医学院科技能力提升项目(2022NLTS066)
中文摘要:目的 采用设计空间法结合质量源于设计理念优化通便凝胶贴剂的提取工艺。方法 以白术内酯Ⅰ、藁本内酯、总黄酮质量分数和浸膏得率等指标为关键质量属性(CQA),采用单因素试验考察浸泡时间、加乙醇量、提取时间、提取次数、乙醇体积分数等因素,在此基础上利用Plackett-Burman试验设计确定关键性工艺参数(CPPs)为提取次数、加乙醇量、乙醇体积分数;采用Box-Behnken设计建立CQA与CPPs的数学模型,设定CQA的控制限度,通过Monte-Carlo仿真法计算获得设计空间并验证分析。结果 构建的数学模型二次项回归拟合模型P<0.05,失拟项>0.1,能较好地描述CQA与CPPs之间的关系,确定最佳提取工艺为浸泡时间45 min、加乙醇量12.0~12.4倍、提取时间60 min、提取数3次、乙醇体积分数52%~57%。结论 优化通便凝胶贴剂提取工艺所得到的理论值与预测值结果接近,表明该法稳定可靠,可为该制剂工业化生产提供参考。
中文关键词:通便凝胶贴剂  设计空间  提取工艺  关键工艺参数  关键质量属性
 
Optimization of Extraction Conditions for Preparation of Catharsis Gel Patch Based on Design Space Method
Abstract:Objective To optimize the extraction conditions of the decoction pieces for the preparation of Catharsis Gel Patch on the basis of the design space method and the conception of quality by design (QbD).Methods The content of atractylenolide Ⅰ, ligustilide, and total flavonoids and the extraction rate were used as critical quality attributes (CQA). The single factor experiments were carried out to investigate the trends of soaking time, ethanol addition amount, extraction time, extraction times, and ethanol concentration. Furthermore, Plackett-Burman design was employed to determine the critical process parameters (CPPs) as extraction times, ethanol addition amount, and ethanol concentration. Box-Behnken design was employed to establish the mathematical model of CQA and CPPs. The control limit of CQA was set, and then the design space was calculated by the Monte-Carlo simulation method and verified.Results The quadratic regression model established in this study showed P<0.05 and the lack-of-fit>0.1, well fitting the relationship between CQA and CPPs. The extraction process was optimized as follows: soaking time of 45 min, ethanol addition amount of 12.0-12.4 volumes that of decoction pieces, extraction time of 60 min, extraction for 3 times, and ethanol concentration of 52%-57%.Conclusion The theoretical value obtained under the extraction conditions optimized by the design space method is close to the predicted value, which shows that the method is stable and reliable and can provide a reference for the industrial production of the preparation.
keywords:Catharsis Gel Patch  design space  extraction process  critical process parameters (CPPs)  critical quality attributes (CQA)
查看全文   查看/发表评论  下载PDF阅读器