Applying Mass Balances to Evaluate the Potential of Hybrid Separation Processes

Within the pharmaceutical industry and in biotechnology there is an increasing need for selective and efficient separation technologies to isolate value added products with a high purity. An important area is for instance the production of enantiomers out of mixtures as they frequently result from synthesis. Often only chromatographic methods yield the desired purity requirements. Unfortunately these methods are rather expensive and their productivity decreased with increasing purity demands1. In contrast, separations based on crystallization are usually less expensive, but often need a certain enrichment to be applicable. The combination of both processes within the design stage gives rise to considerable optimization potential. First general results were already demonstrated, e.g. for the separation of enantiomers2. A possible flowsheet of such a hybrid separation process is shown below. Depending on the concrete separation problem units may be added or subtracted from this scheme. Each of the units involved possess its specific dynamics and limitations. To quantify completely such coupled processes requires large experimental and modelling efforts. Finally it might turn out that the hybrid process (chromatography and crystallization) does not even have the potential to be superior over the single chromatographic separation. In this presentation a general approach based on analytical solutions of mass balance equations will be proposed using several examples for illustration. The advantage of the approach suggested is an a priori evaluation of the potential of a hybrid process for a specific separation problem in the early design stage. The analysis does not need detailed knowledge related to kinetic parameters and other processes involved (e.g. solvent treatment). For the description of coupling chromatography and crystallization no additional tools are required besides a valid model of the chromatographic process and limiting composition necessary for fractional crystallization. With this concept in the early design stage a decision can be drawn whether the coupled process can be more advantageous then chromatography alone. 1. Kaspereit et al., Journal of Chromatography A, 944 (2002), 249-262 2. Lorenz et al., Journal of Chromatography A, 908 (2001), 201-21