Studies On The Ethanol Extraction Process And The Water Precipitation Process For The Manufacturing Of Panax Notoginseng Preparations

Quality by design (QbD) is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management. Development of design space is one of the key components of the implementation of QbD concept. The main contents and achievements of this thesis are summarized as follows:1. Design space of extraction process was established. According to the results of fishbone chart and Failure Mode and Effects Analysis (FMEA), ethanol content (EC), amount of ethanol added (AEA), extraction time (ET) and number of extraction (NE) are identified as the critical process parameters (CPPs) of the ethanol extraction process. Box-Behnken design were carried out to develop models between CPPs and critical quality attributes (CQAs). Design space was calculated using a Monte Carlo simulation method. Normal operation ranges to attain process CQA criteria with a probability more than 94% are recommended as follows:NE of 2, EC of 84.0-86.0%, AEA of 5.0-7.0 mL/g and ET of 7.0-8.0 h.2. Design space of water precipitation process was established. An Ishikawa diagram and experiments of fractional factorial design were applied to determine CPPs. Dry matter content of concentrated extract (DMCC), amount of water added (AWA), and stirring speed (SS) were identified as CPPs. Box-Behnken design were carried out to develop models between CPPs and CQAs. Design space was calculated using a Monte Carlo simulation method. Normal operation region are located in DMCC of 0.38-0.41 g/g, AWA of 3.7-4.9 g/g, and SS of 280-350 r/min, with a probability more than 91.94% to satisfy CQAs criteria. The incomplete collection of supernatant is the main reason for the loss of saponins.3. Adjusted method of CPPs for water precipitation process considering the critical material attributes (CMAs) of process materials was studyed. Stepwise regression were carried out to develop models among CMAs, CPPs and CQAs. Saponin contents, including notoginsenside Ri, ginsenoside Rgi, ginsenoside Re, ginsenoside Rbi and ginsenoside Rd, in the dry matter of concentrate was found to be CMAs. After that, design sapce can be calculated according to the variations of the materials. Finally, a CPPs control strategy to ensure the efficiency of water precipitation process and quality consistency of supernatant was put forward.