基于质量源于设计理念的金银花水提液石灰乳沉淀工艺优化研究

Optimization of lime milk precipitation process of Lonicera Japonica aqueous extract based on quality by design concept

该研究采用设计空间法优化金银花水提液的石灰乳沉淀工艺。该工艺的评价指标为6种有机酸总纯度和单位质量药材提取出的6种有机酸量。通过加权标准偏回归系数法筛选出碱液滴加速度、调碱pH、静置时间和静置温度为4个关键工艺参数。采用逐步回归法建立工艺评价指标与关键工艺参数的定量模型。通过Monte Carlo算法计算出基于概率的设计空间并进行验证。结果表明,在设计空间内操作能够保证石灰乳沉淀工艺品质稳定。该研究推荐石灰乳沉淀工艺操作空间为:碱液滴加速度1.00~1.25 mL·min^(-1),调碱pH 11.5~11.7,静置时间1.0~1.1 h,静置温度10.0~20.0℃。

Design space approach was applied in this study to optimize the lime milk precipitation process of Lonieera Japonica （Jinyinhua） aqueous extract. The evaluation indices for this process were total organic acid purity and amounts of 6 organic acids obtained from per unit mass of medicinal materials. Four critical process parameters （CPPs） including drop speed of lime milk, pH value after adding lime milk, settling time and settling temperature were identified by using the weighted standardized partial regression coefficient method. Quantitative models between process evaluation indices and CPPs were established by a stepwise regression analysis. A design space was calculated by a Monte-Carlo simulation method, and then verified. The verification test results showed that the operation within the design space can guarantee the stability of the lime milk precipitation process. The recommended normal operation space is as follows ： drop speed of lime milk of 1.00-1.25 mL · min^- 1 , pH value of 11.5-I 1.7, settling time of 1.0-1.2 h, and settling tem- perature of 10-20℃.