The crystallization work at the institute is directed to the two general objective functions of crystallization processes:

• the product design and
• the separation of mixtures.

The product design in terms of getting a disperse phase of desired characteristics (e.g. a definite particle size distribution) is of special interest in case of gaining bulk crystallization products like inorganic salts and organic intermediates. In this frame the work carried out implies modelling, simulation and control of batch and continuous crystallization processes. Theoretical calculations are supported by experiments using the pilot scale crystallizer.

On the other hand crystallization methods are very powerful separation techniques. Their applicability and potential to produce pharmaceuticals, particularly pure enantiomers, is another field of interest at the Max-Planck-Institute. In relation to the project area Integrated processes, one focus is laid on designing a crystallization based hybrid approach for enantioseparation in order to significantly increase the productivity for the entire process. The problem is studied on a theoretical and experimental basis using pharmaceutical relevant systems, e.g. in cooperation with the Bayer Schering Pharma AG (Berlin). Further, fundamental physical and chemical data required for crystallization purposes are determined and measurement techniques for crystallization monitoring are tested and adapted.

Dependent on the system studied, various batchwise operated crystallization facilities from 50 ml up to 20 l reactor volume are available. A crystallization test rig in continuous mode that allows experiments with product classification and fines dissolution is under construction. The reactors may be equipped with various in-, on- and offline measurement techniques to analyze temperature, solution concentration (supersaturation), enantiomeric excess, particle size etc. Reactor operation and data acquisition are supported using a process control system.

Some of the topics we deal with are the following:

• Measurement techniques for monitoring and investigation of crystallization processes,
• Solid-liquid equilibria for design and optimization of crystallization processes,
• Crystallization kinetics particularly crystal growth,
• Crystallization based hybrid approaches for efficient enantioseparation,
• Advanced crystallization based enantioseparation concepts (e.g. innovative process strategies of preferential crystallization and extension of applicability, application of optically active solvents),
• Nonlinear dynamics of crystallization processes,
• Control of crystallization units.

These tasks are handled interdisciplinarily in teamwork of the different research groups and in cooperation with the companies and universities mentioned above.

Selected References

Lorenz, H., Seidel-Morgenstern, A.: A contribution to the mandelic acid phase diagram. Thermochimica Acta 415 (2004), pp.55–61

Elsner, M. P., D. Fernández Menéndez, E. Alonso Muslera and A. Seidel-Morgenstern: Experimental study and simplified mathematical descriptionof preferential crystallization. Chirality 17, S183-S195 (2005a)

Gedicke, K., W. Beckmann, A. Brandt, D. Sapoundjiev, H. Lorenz, U. Budde and A. Seidel-Morgenstern: Coupling Chromatography and Crystallization for Efficient Separations of Isomers, Adsorption 11, (2005), pp. 591-596

Lorenz, H., Beckmann, W., Budde, U., Sapoundjiev, D., Seidel-Morgenstern, A.: Partial miscibility in the solid state - experimental accessibility and independent corroboration: a case study on a diastereomeric intermediate. VDI-Berichte 1901 (2005), pp. 91–96

Önçül, A. A., K. Sundmacher, A. Seidel-Morgenstern and D. Thévenin: Numerical and analytical investigation of barium sulphate crystallization. Chemical Engineering Science, in print (2005a)

Perlberg, A., H. Lorenz and A. Seidel-Morgenstern: Crystal Growth Kinetics via Isothermal Seeded Batch Crystallization: Evaluation of Measurement Techniques and Application to Mandelic Acid in Water. Industrial and Engineering Chemistry Research 44, 1012-1020 (2005)

Perlberg, A., Lorenz, H., Seidel-Morgenstern, A.: Aspects of crystal growth in chiral systems on the example of mandelic acid in water. VDI-Berichte 1901 (2005), pp. 689–694

Lorenz, H., A. Perlberg, D. Sapoundjiev, M. P. Elsner and A. Seidel-Morgenstern: Crystallization of enantiomers. Chemical Engineering and Processing, 45 (2006), pp. 863-873

Beckmann, W., Lorenz, H.: Partial miscibility of organic compounds in the solid state – the case of two epimers of a diastereomer. Chem. Eng. Technol. 29, (2006), pp. 226-232

Polenske, D., M. P. Elsner, H. Lorenz and A. Seidel-Morgenstern: Alternative Einsatzmöglichkeiten der „Bevorzugten Kristallisation“ zur Enantiomerentrennung. Chemie-Ingenieur-Technik, 78 (2006), pp. 1101-1110

Czapla F., Lorenz H., Elsner M. P., Seidel-Morgenstern A.: Einfluss der Prozessführungsstrategie auf Produktivität und Produkteigenschaften einer “Bevorzugten Kristallisation”. In Teipel, U. (Hrsg.): Produktgestaltung in der Partikeltechnologie, Band 3, Fraunhofer-IRB-Verlag, Stuttgart, 2006, S.219-235

Lorenz H., Polenske D., Seidel-Morgenstern A.: Application of Preferential Crystallization to Resolve Racemic Compounds in a Hybrid Process. Chirality, 18 (10), 2006, 828 – 840

Lorenz H., Czapla F., Polenske D., Elsner M. P., Seidel-Morgenstern A.: Crystallization based separation of enantiomers. Journal of the University of Chemical Technology and Matallurgy, 42 (1), 2007, 5-16

Lorenz, H., Elsner, M. P., Polenske, D., Czapla, F., Seidel-Morgenstern, A.: Gut kombiniert – Online-Monitoring kristallisationsbasierter Trennungen. PROCESS 7/8 (2007), S. 40–41

Gedicke, K., Kaspereit, M., Beckmann, W., Budde, U., Lorenz, H., Seidel-Morgenstern, A.: Conceptual design & feasibility study of combining continuous chromatography and crystallization for stereoisomer separations. Chem. Eng. Res. Des. 85 (2007), pp. 928–936

Tulashie, S., Lorenz, H., Hilfert, L., Edelmann, F. T., Seidel-Morgenstern, A.: Potential of chiral solvents for enantioselective crystallization. 1. Evaluation of thermodynamic effects. Crystal Growth & Design 8 (2008), pp. 3408–3414

Tulashie, S., Lorenz, H.,Seidel-Morgenstern, A.: Potential of chiral solvents for enantioselective crystallization. 1. Evaluation of kinetic effects. Cryst. Growth & Design accepted

Kaemmerer, H., Lorenz, H., Black, S., Seidel-Morgenstern, A.: Study of system thermodynamics and the feasibility of chiral resolution of the polymorphic system of malic acid enantiomers and its partial solid solutions. Crystal Growth & Design, accepted

Qamar, S.; Warnecke, G.; Elsner, M.P. (2008): Numerical simulation of population balances for combined particulate processes. Chem. Eng. Sci. (submitted)

Qamar, S.; Warnecke, G.; Elsner, M.P. (2009): On the solution of population balances for nucleation, aggregation and breakage processes. Chem. Eng. Sci. (in press)

Patents

Seidel-Morgenstern, A., Lorenz, H., Polenske, D.: Verfahren zur Trennung verbindungsbildender chiraler Systeme. Patent DE 10 2005 039 501 A1, Offenlegungstag: 22. 02. 2007

Seidel-Morgenstern, A., Lorenz, H., Polenske, D.: Method für separating compound-forming chiral systems. Internationales (PCT) Patent WO 2007/023129 A2, Veröffentlichung: 01. 03. 2007

Lorenz, H., Kaemmerer, H., Polenske, D., Seidel-Morgenstern, A.: Process for enantioseparation of chiral compound forming systems using two subsequent crystallization steps. Patent angemeldet: 05. 09. 2008