APPLICATIONS OF SIMULATED MOVING-BED CHROMATOGRAPHY TO THE SEPARATION OF THE ENANTIOMERS OF CHIRAL DRUGS

摘要

Although most preparative chiral separations have been performed in the conventional batch-mode process, interest in simulated moving-bed (SMB) chromatography is growing, because it permits large amounts of mobile phase to be saved and productivity increased, thus reducing production costs. Based on the examples of three different drugs, the usefulness of this technique for the separation of enantiomers on a preparative scale has been demonstrated. Compared to the batch elution chromatography, a reduction of the mobile phase consumption of respectively 81% and 84% has been achieved for the separation of the enantiomers of the antiasthmatic agent formoterol and of the antitussive agent guaifenesin. Furthermore, a higher throughput could be reached under SMB conditions. The influence of feed rate and extract on the separation has also been investigated. The results show that these two factors considerably affect purity and productivity, and constitute important parameters for finely adjusting the chromatographic conditions depending on the requirements. For all racemates, both enantiomers could be obtained with a purity ranging between 99 and 99.9%.