The separation of enantiomers by chromatography is a field expanding significantly due to the increasing interest for pure enantiomers in the pharmaceutical industry.
Technological advances regarding the chromatographic systems and the availability of bulk chiral stationary phases (CSPs) with excellent batch-to-batch reproducibility account for the growing number of industrial applications in this area.
When the scale-up of a separation is envisaged, the choice of the suitable CSP, together with the appropriate mobile phase and operating conditions become the critical points. The CSP should show a suitable enantioselectivity for the target compound to be resolved, as well as a high loading capacity, to make the separation feasible at large scale.
However, these are not the only requirements which have to be fulfilled: robustness, chemical inertness and thermal stability of the CSP and the enantiomers under the separation conditions are also crucial issues.
Concerning costs, the investments needed and productivity become essential questions. The important achievements reported in the field of enantiomer separations with Daicelpolysaccharide-derived CSPs in continuous chromatographic systems, such as simulated moving bed (SMB), account for the high potential of chromatographic techniques.
Chromatographic screening on the commercially available Chiralcel and Chiralpak columns is currently performed by Chiral Technologies as a practical tool to identify the best separation for a given compound. Most recently, this screening has been broaden to an extensive polysaccharide-derived aCSP library' (more than 50 different CSPs), for industrial scale projects.
As a crucial part of the customer support, the main goal of the CSP library approach is the identification of the optimal combination aCSP plus chromatographic conditions' leading to the highest productivity rates(kg enantiomer/kg CSP/day) for a specific compound. A higher productivity might have an impact on the size of the chromatographic system to be used, the labour, energy and solvent needed. Therefore, it would have direct consequences in the reduction of production time and costs.
This broader choice of CSPs might not only introduce new selectivity profiles but also the use of different solvent mixtures as mobile phases, which may improve the solubility of the racemic compounds to be separated. Enhancements in productivity over 4.5-fold have been achieved using the CSP library for certain compounds in single-column chromatography.
Furthermore, the results of this extensive screening have been applied to multi-column systems, such as SMB.The substitution of a commercially available CSP by a support from theCSP library was increasing productivity 2 or even 3 times for some pharmaceutical compounds of interest by SMB(see Fig. 1).
These successful results demonstrate that the CSP library is a promising concept to enhance productivity in the industrial separation of enantiomers.
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Chiral Technologies Europe is based in Illkirch Cedex, France. www.chiral.fr
