Study on the metastable zone width of ketoprofen

Abstract

With increasing awareness for the need of pure enantiomer drugs, strong emphasis has been focused on the research of chiral drug separation. Compared with other separation methods, crystallization is a simple and economical method, and the metastable zone width (MSZW) is a very important factor for the entire crystallization process. In this paper, the effects of the metastable zones of (R,S)- and (S)-ketoprofen and a 0.94 mole fraction of (S)-ketoprofen in order to enhance the MSZW were studied. Four main factors were studied, namely, temperature, cooling rate, stirring rate, and volume ratio of mixed solvent (water/ethanol). Through the L9 fractional experiment design, it was observed that all samples' MSZWs would increase with an increase in cooling rate and decrease with an increase in the ethanol volume ratio and temperature. The ethanol ratio may have the strongest effect on the process and can greatly enhance the metastable zone, and the other three factors influence the MSZW only slightly. In conclusion, the these four factors for enhancing MSZW have been optimized: water-to-ethanol volume ratio, 1:0.6; temperature, 20 degrees C; stirring rate, 700 rpm; and cooling rate, 12.0 degrees C/h. All of these results will be helpful for the following chiral separation of ketoprofen by crystallization.