Optimization of lime milk-sulfuric acid process of Salviae Miltiorrhizae Radix et Rhizoma aqueous concentrate based on quality by design concept
10.7501/j.issn.0253-2670.2019.10.008
- Author:
Wen-Zhu LI
1
Author Information
1. Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University
- Publication Type:Journal Article
- Keywords:
Central composite design;
Critical process parameters;
Critical quality attribute;
Danshen Chuanxiongqin Injection;
Design space;
Fishbone diagram;
Lime milk-sulfuric acid purifying process;
Plackett-Burman design;
Quality by design;
Quality consistency;
Risk assessment;
Salviae Miltiorrhizae Radix et Rhizoma;
Salviae Miltiorrhizae Radix et Rhizoma aqueous concentrate
- From:
Chinese Traditional and Herbal Drugs
2019;50(10):2302-2311
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To optimize the lime milk-sulfuric acid process of Salviae Miltiorrhizae Radix et Rhizoma (SMRR) aqueous concentrate in the pretreatment of the manufacture of Danshen Chuanxiongqin Injection (DCI) based on the quality by design (QbD) concept. Methods Fishbone diagram method was applied to conduct preliminary risk assessment of various process parameters in lime milk-sulfuric acid process of SMRR aqueous extracts. Nine potential critical process parameters (CPP), including mass fraction of lime milk, flow rate of the lime milk addition, stirring speed, stirring time after lime milk addition, mass fraction of sulfuric acid, flow rate of the acid addition, stirring time after acid addition, standing time, and standing temperature, were identified. Plackett-Burman (PB) experiment design method was used to further screen the nine potential CPPs. As the result, the mass fraction of lime milk, stirring time after lime milk addition, stirring time after acid addition, and the standing time were filtered as CPPs of the lime milk-sulfuric acid process. A partial least squares regression models of critical process parameters and critical quality attributes were established using the central composite design and the design space methodology. Results: The recommended operation space of the lime milk-sulfuric acid process in the pretreatment of the manufacture of DCI was as follow: mass fraction of lime milk of 12.0%-13.0%, stirring time after lime milk addition of 40-50 min, stirring time after acid addition of 30-35 min, and standing time of 16-20 h. Conclusion: Operation in the design space is helpful to improve the consistency of lime milk-sulfuric acid process. This study is of valuable reference to actual industrial production.
