Simulated Moving Bed (SMB) Separation of Pharmaceutical Enantiomers and Crystallization

Abstract

A promising solution for the separation of pharmaceutical enantiomers is the method of SMB liquid chromatography (SMB-LC). An optimised coupling of SMB-LC and crystallization processes can improve the efficiency of enantioseparation. In the first process both enantiomers can be produced in enriched concentrations in extract and raffinate streams of simulated moving bed chromatograph suitable for crystallization. Chromatographic investigations include the experimental determination of adsorption isotherms, bed voidage, NTP, HETP etc. on a suitable chiral stationary phase as well as the simulation and optimization of a the appropriate SMB-LC process. Mathematical models and joined computer programmes were published in our earlier papers had been developed and applied for the calculation of SMB-LC. We assumed isotherm, isochor equilibrium adsorption (competitive multicomponent Langmuir-adsorption equilibrium) in the mathematical model neglecting the effects of axial dispersion. The mathematical model was solved by finite differences, numerical mathematical method using PC. The SMB-LC separations were carried out on a laboratory scale (I.D.=1 cm, L=25 cm) four-column open loop eluent system equipment at 1:1:1:1 column configuration. The process variables of the SMB-LC (product purity, yield, productivity, specific solvent consumption) are favourable. The efficiency of the enantiomer separation can be increased by coupled crystallization of the enriched extract and raffinate fractions resulting >99% (w/w) pure enantiomer crystals. „Mother liquids” recirculation from crystallization to the SMBLC process increases with great benefit the economical parameters of enantiomer separation.