PD Dr. M. Johannsen

The increasing demand on purity of pharmaceutical substances takes up the application of effective separation techniques for production of high value products. Hereby preparative chromatography is of increasing importance as a high selective thermal separation process. Under certain conditions conventional organic solvents, as used in most industrial chromatographic separations, can be replaced by environmentally friendly supercritical fluids (e.g. carbon dioxide). One essential advantage of using supercritical fluids is the easy product recovery by depressurizing the supercritical fluid without any additional rectification step.

Supercritical fluid chromatography (SFC) is an attractive alternative to High pressure liquid chromatography (HPLC) with polar or chiral stationary phases and nonpolar organic solvents. Besides chromatography in elution mode on a single column (batch chromatography) continuous processes like the Simulated Moving Bed (SMB) process are of increasing interest. The SMB with supercritical fluids (SMB-SFC) combines the advantages of preparative SFC with the ones of the SMB technique that means it is a continuous process with a high specific productivity, especially for binary separations.

The Institute of Thermal and Separation Processes is the worldwide largest academic centre for high pressure technology. A large number of excellent equipment for high pressure and high temperature applications at different scales for reaction and separation processes as well as for the determination of fundamental thermodynamic data (e.g. phase equilibria) is available. For chromatographic separations a preparative supercritical fluid chromatography (SFC) for elution mode (column: 30 mm ID, 450 mm max. length) and a Simulated Moving Bed (SMB)-SFC (8 columns: each 30 mm ID, 190 mm max. length) have been built and put into operation. With both instruments the separation of up to 1 kg feed per day is possible.

Abb. 1: Preparative SFC


Fig. 2: SMB-SFC

In previous works a systematic procedure for the development of preparative chromatographic processes and models for the adsorption chromatography with supercritical fluids were developed. A comprehensive program package was obtained which allows the optimization of chromatographic separations. Separations of polyunsaturated fatty acids (PUFAs), phytol isomers, ibuprofen enantiomers, and tocopherol homologues were experimentally realized successfully and further investigated by simulations.

In ongoing investigations on process development and optimization of SFC for separation of high value products, fundamental data (e.g.adsorption equilibria) are determined first. After that, a simulation of the process is necessary for process optimization. Finally the results from simulations are compared with the results from experimental separations, achieved by the preparative SFCs at the institute.