title: Design space development for the extraction process of Danhong injection using a Monte Carlo simulation method.
abstract: A design space approach was applied to optimize the extraction process of Danhong injection. Dry matter yield and the yields of five active ingredients were selected as process critical quality attributes (CQAs). Extraction number, extraction time, and the mass ratio of water and material (W/M ratio) were selected as critical process parameters (CPPs). Quadratic models between CPPs and CQAs were developed with determination coefficients higher than 0.94. Active ingredient yields and dry matter yield increased as the extraction number increased. Monte-Carlo simulation with models established using a stepwise regression method was applied to calculate the probability-based design space. Step length showed little effect on the calculation results. Higher simulation number led to results with lower dispersion. Data generated in a Monte Carlo simulation following a normal distribution led to a design space with a smaller size. An optimized calculation condition was obtained with 10,000 simulation times, 0.01 calculation step length, a significance level value of 0.35 for adding or removing terms in a stepwise regression, and a normal distribution for data generation. The design space with a probability higher than 0.95 to attain the CQA criteria was calculated and verified successfully. Normal operating ranges of 8.2-10 g/g of W/M ratio, 1.25-1.63 h of extraction time, and two extractions were recommended. The optimized calculation conditions can conveniently be used in design space development for other pharmaceutical processes.
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xingchu
authors.initials: X
authors.lastname: Gong
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Huali
authors.initials: H
authors.lastname: Chen
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Haibin
authors.initials: H
authors.lastname: Qu
mesh_terms: D002316:Cardiotonic Agents / Q000302:isolation & purification*; D031187:Carthamus tinctorius / Q000737:chemistry; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000302:isolation & purification*; D005163:Factor Analysis, Statistical; D006801:Humans; D009010:Monte Carlo Method; D012044:Regression Analysis; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D052616:Solid Phase Extraction / Q000379:methods*; D014867:Water / Q000737:chemistry
chemical_list: D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; C540581:danhong; D014867:Water; C079426:Honghua extract, Carthamus tinctorius