Establishment of extraction design space for ursolic acid from Paulowniae Flos based on the concept of quality by design.

ABSTRACT

INTRODUCTION: The application of quality by design (QbD) concept needs to be strengthened in the field of traditional Chinese medicine research. The extraction process has an important influence on the effectiveness of the drug, and the combination of QbD and the extraction process of the active ingredient helps to improve the effectiveness of the drug. OBJECTIVE: To establish the extraction design space for ursolic acid (UA) from Paulowniae Flos based on the concept of QbD. METHODS: The extraction yield of the target component UA was taken as critical quality attributes (CQAs), extraction time, extraction temperature, ethanol concentration and liquid-solid ratio, as critical process parameters (CPPs). Box-Behnken design (BBD) was applied to optimise the design space and the chromatographic conditions were performed on a Shimadzu C18 reversed-phase column with 0.1% (v/v) acetic acid aqueous water-acetonitrile (713, v/v) as the mobile phase at a 1 mL/min flow rate, using UA standard as a control and detection at 210 nm. RESULTS: The single factor investigation and BBD experiment were used to construct the design space, while verification experiments and methodological validation were used to demonstrate that the space was robust and analytical methods were appropriate. The operating space of ethanol concentration 93-98%, liquid-solid ratio 28-37 mL/g and extraction temperature 70-78.3°C was recommended. CONCLUSION: The proposed methodology can help to promote the quality control of the Chinese medicine extraction process and facilitate the production operation of the enterprise easier.