(577a) A Scale-Down and Feedback-Control Based Methodology to Optimize Multi-Step Extraction for Botanical Preparation on the Commercial Scale

A systematical methodology from a commercial scale extraction apparatus to laboratory scale based on scale-down and feedback-control strategy was established to optimize the water-extraction process in the manufacturing of a botanical preparation, named as Xutong injection in China, on a commercial scale. The raw material of this preparation is Salvia Miltiorrhiza. Firstly, quality by design principle was used to achieve process characterization and process optimization of the water-extraction process in a scale-down of 2 L extractor. Several main quality markers of Salvia Miltiorrhiza were evaluated to determine the optimal formulation, including the extraction rate of phenolic acids as the effective components and the extraction rate of polysaccharides as the impurities. Secondly, the operation space of process parameters was optimized using a central composite design with response surface methodology as follows: Salvia Miltiorrhiza root length was11 cm, the ratio of solvent to raw material was 10 mL / g and each extraction time was 70-90 min for twice. Then, the optimized parameters were applied to make reproducibility test in a commercial scale of 4,000L extractor. In this phase, through in-line data collection, a feedback control strategy was implemented in the pilot production to achieve process real-time determination and control. Finally, the extracting solution manufactured in the commercial-scale process was compared with pre-existing extracting solution collected in the prior batches, which was verified of higher quality and process efficiency. More than 22% active ingredients were extracted than ever. The proposed methodology in this work, once applied to a commercial botanical preparation, is of significant value for continuous improvement in the aspect of reducing time and cost, decreasing batch-to-batch variability and realizing real time release.