(145a) Study on Crystallization Phase Diagrams and Kinetics Behaviors of Ketoprofen
AIChE Annual Meeting
Monday, November 13, 2006 - 3:20pm to 3:40pm
With increasing awareness for the need of pure enantiomer drugs, strong emphasis has been focused on the research of chiral drug separation. Compared to the simulated moving bed (SMB) chromatography, fractional crystallization is a simple and economical method for the enantioseparation. Therefore, the coupling of SMB chromatography and fractional crystallization is suggested for enantioseparation of racemic compounds. In this paper, a nonsteroidal anti-inflammatory drug, ketoprofen (Kp), was chosen to be studied. Kp was verified as racemic compound by FTIR, PXRD and some thermodynamic calculations. To derive the condition where pure (S)-Kp could be crystallized from a solution, which has been previously enantiomerically enriched, the binary melting phase diagram and the ternary solubility phase diagram in the mixed solvent of ethanol and water over the temperature range from 15oC to 30oC were obtained. From these phase diagrams, the eutectic point was determined as 91.6% mole percent (S)-Kp from the binary phase diagram and 91% from the ternary phase diagram. In addition, in designing operation conditions for a crystallizer to efficiently generate the required product crystals, crystallization kinetic date, such as linear growth rate G and nucleation rate B, are very important. According to the population balance equation under unsteady state, the linear growth rate G and nucleation rate B of (R, S)-Kp and (S)-Kp were determined by a moment analysis method. The parameter of crystallization kinetics equations were estimated by regression of experimental data. The results from this paper may provide valuable experiment data for the possibility of coupling of fractional crystallization with SMB for the Kp separation.