Optimization of Panax notoginseng extraction process using a design space approach

Health foods containing Panax notoginseng extract are developed in recent years. In this work, reflux extraction process was optimized using a design space approach to improve batch-to-batch consistency of P. notoginseng extract. Saponin yields and dry matter yield were identified as the process critical quality attributes (CQAs) of the extraction process. A risk assessment was applied to determine critical process parameters (CPPs), which were ethanol content (EC), amount of ethanol added (AEA), extraction time (ET) and extraction frequency (EF). Box-Behnken designed experiments were carried out to develop models between CPPs and process CQAs. Determination coefficients were higher than 0.90 for all the models. Higher ET, EF, and AEA all result in higher saponin yields and dry matter yield. Dry matter yield decrease as EC increases. Design space was calculated using a Monte-Carlo simulation method with the acceptable probability of 0.85. Normal operation ranges to attain process CQA criteria with a probability more than 94% are recommended as follows: EC of 84.0-86.0%, AEA of 5.0-7.0 mL/g, ET of 7.0-8.0 h, and EF of 2. Verification experiment results showed that operating EC, AEA, EF and ET within design space can attain CQA criteria. Most of the verification experiment results agreed well with prediction results, which means that the developed models are accurate and applicable in a larger scale extraction process.