Assessment of coupling chromatography and crystallization for productivity enhancement
Special Symposium - EPIC-1: European Process Intensification Conference - 1
EPIC-1: Multifunctionality (MF-3)
Keywords: Crystallization, Chromatography, Enantioseparation, Process intensification
Among all enantioseparation methods the enantioselective preferential crystallization [1] is an attractive and inexpensive possibility for mixtures which reveals for a conglomerate typical phase diagram i.e., a physical mixture of enantiopure crystals. In solution such systems tend to reach an equilibrium state in which the liquid phase will have racemic composition and the solid phase will consist of a mixture of crystals of both enantiomers. However, before approaching this state, it is possible to preferentially produce just one of the enantiomers after seeding with homochiral crystals
Preferential crystallization processes are sometimes carried out with an initial concentration excess of the preferred enantiomer. To produce such an excess chromatographic process can be employed. It will be shown that by integrating preferential crystallization with batch chromatography higher process productivity can be achieved. Such a complex integrated process requites proper design to be successfully conducted on an industrial scale. The objective of this work was to analyze and optimize operating parameters of chromatography and simultaneous preferential crystallization [2].
The theoretical investigations of the crystallization process were based on a simplified mathematical model deriving under assumption of ideally mixed batch crystallizer, of size independent rate of the crystal growth and of negligible coalescence, attrition or agglomeration. The kinetic parameters of the model were determined experimentally for the threonine-water system [3].
In order to produce the initial enantiomeric excess the chromatographic process was properly designed. To generate the mobile phase composition adequate for enantio-separation as well as for the subsequent process of crystallization the gradient elution has been selected as the operating mode. For evaluation and optimization of the dynamics of chromatographic process the equilibrium-dispersive model [4] was applied. The model parameters such as isotherm coefficients and kinetic parameters were determined experimentally.
In this presentation the optimized process parameters for both the unit processes as well as for the integrated process will be given. Parallel to the theoretical analysis, an experimental validation of the process will be also presented.
[1] Elsner, M.P., Fernández Menéndez, D., Alonso Muslera, E., Seidel-Morgenstern, A. (2005): Experimental study and simplified mathematical description of preferential crystallization, Chirality 17 (S1), S183-S195
[2] Kaspereit, M. (2006): Separation of Enantiomers by a Process Combination of Chromatography and Crystallisation. PhD thesis, Otto von Guericke University, Magdeburg
[3] Elsner, M.P., Ziomek, G., Seidel-Morgenstern, A. (2007): Simultaneous preferential crystallization in a coupled, batch operation mode. Part I: Theoretical analysis and optimization. Submitted to Chemical Engineering Science.
[4] Ziomek, G., Antos D., Tobiska L., Seidel-Morgenstern A. (2006): Comparison of possible arrangements of five identical columns in preparative chromatograph. Journal of Chromatography A, 1116, 179-188
Presented Thursday 20, 14:40 to 15:00, in session EPIC-1: Multifunctionality (MF-3).
