Modification of a commercial chiral stationary phase - Influences on enantiomer separations using simulated moving bed chromatography

Chromatographic enantiomer separations using high-performance chromatograph y and the simulated moving bed (SMB) principle have become a practically us eful method for obtaining optical isomers. The carbamate derivatives of amy lose coated onto silica particles are very effective chiral stationary phas es (CSPs). Several lots of Chiralpak(R) AS(TM), and its successor, Chiralpa k(R) AS-V(TM), were compared by laser diffraction, microscopic imaging and pulse injections with increasing amounts of various racemates in order to d etermine the loading capacity and the competitive adsorption isotherms. Sof tware simulations allowed to assess the possible effects due to the observe d variations between the CSPs on the performance of a pilot SMB unit. The o btained results were verified by two multi-kilogram separations performed u nder current good manufacturing principles (cGMP) guidelines employing the two CSPs. The results of the two production runs are discussed in the tight of the recently introduced "triangle theory" which allows to account for t he overload conditions prevailing under preparative chromatographic conditi ons and to predict optimal operating conditions. Under optimized conditions the enantiomer separation of 1.4 kg racemate/kg stationary phase per day w ith purities >99.6% for the target enantiomer have been achieved. (C) 2001 Elsevier Science B.V. All rights reserved.