Chiral Separation of Ketoprofen Enantiomers by Preparative and Simulated Moving Bed Chromatography

Abstract

Abstract The pharmaceutical industry is now directed to the market of more safety and efficient drugs, based on single enantiomers. Ketoprofen, still used as a racemic pharmaceutical drug, belongs to the profens class, one of the most representative of the non-steroidal anti-inflammatory drugs. This work presents the chiral separation of ketoprofen enantiomers by simulated moving bed technology, using a laboratory scale unit (the FlexSMB-LSRE®) with six columns, packed with the Chiralpak AD® stationary phase (20 μm). A comparative study between a mobile phase composed of a traditional high hydrocarbon content (10%ethanol/90%n-hexane/0.01%TFA) and a strong polar organic composition (100%ethanol/0.01%TFA) is presented. The study includes the measurement of the adsorption isotherms, elution, and frontal chromatography experiments, carried out on a SMB column for both compositions. The results obtained allowed the prediction and optimization of the SMB operation. Using pure ethanol as solvent and a racemic feed concentration of 40 g/L, purities above 98.6% on both outlet streams were obtained, with a productivity of 3.84 gfeed/(Lbed.hr) and a solvent consumption of 0.78 Lsolvent/gfeed. The results obtained in the experimental separation of ketoprofen enantiomers by SMB chromatography indicates that pure ethanol presents better performances than the classic high hydrocarbon content composition. Keywords: ketoprofenpreparative chiral separationsimulated moving bed chromatographysolvent composition ACKNOWLEDGEMENTS Financial support by the Portuguese R&D foundation FCT (Fundação para a Ciência e a Tecnologia) and European Community through FEDER (project POCI/EQU/59738/2004), is gratefully acknowledged. The authors wish thank to Rufino Amaro (Polytechnic Institute of Bragança) for his support in the deployment of simulations in the High Performance Computing cluster of the Laboratory of Informatics. Notes M is the number of experimental points; N is the number of parameters; m 1, m 2, Q, b 1, and b 2 are the estimated parameters for each isotherm model: LG3-Langmuir; LLG4-linear + Langmuir (m 1 = m 2); LLG5-modified linear + Langmuir (m 1≠m 2); SQ is the sum of squares of the residues and SD is the standard deviation.