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The paper deals with chiral separation by simulated moving bed (SMB) chromatography. The separation of chiral epoxide enantiomers in microcrystalline cellulose triacetate using methanol as eluent is considered as illustrative example. The use of microcrystalline cellulose triacetate for the chromatographic separation of enantiomers is first reviewed and a methodology for obtaining basic data (adsorption equilibrium isotherms, axial dispersion and mass transfer coefficient) is discussed. A model for the prediction of the cyclic steady-state performance of the SMB, based on the analogy with the true moving bed, is developed assuming multicomponent adsorption equilibria, axial dispersion flow and linear driving force approximation to describe the intraparticle mass transfer rate. The simulation package is used to predict the effect of operating variables on the process performance and to define the regions for enantiomer separation. A simple optimization procedure is proposed for choosing the best SMB operating conditions. This procedure is extensively tested for the separation of chiral epoxide enantiomers. The experimental operation of a SMB pilot unit was carried out for this system. Purities and recoveries higher than 90% were obtained for both extract and raffinate, using a 420 ml inventory of stationary phase. The SMB pilot allows the continuous resolution of 52 g of racemic mixture per day and per liter of bed, with a solvent consumption of 0.4 l of mobile phase per gram of racemic mixture processed. The simulation package is also used to predict the steady-state internal concentration profiles for the SMB operation with reasonable agreement with experimental results.

Abstract--The chromatographic separation of 1,1'-bi-2-naphthol enantiomers with 3,5-dinitrobenzoyl phenylglycine bonded to silica gel stationary phases is studied. Continuous chromatography in simulated moving bed (SMB) is analyzed by modeling, simulation and operation of a SMB pilot unit Licosep 12-26 from Separex (France).A model for the prediction of the cyclic steady-state performance of the SMB is developed based on the analogy with the true moving bed (TMB). The model assumes axial dispersion flow for the liquid phase, linear driving force (LDF) approximation for intraparticle mass transfer rate and takes into account multicomponent adsorption equilibria.The SMB package allows the simulation of the pilot unit. The effect of operating variables (switching time, extract and feed flow rates, section length) and number of mass transfer units on the SMB performance is analyzed. The SMB performance is characterized by purity, recovery, solvent consumption and adsorbent productivity. The package also allows the simulation of the dynamic evolution of internal profiles for the transient operation of a TMB. The operation of the SMB pilot unit was carried out for the separation of racemic mixtures of bi-naphthol enantiomers. Using a 8-column configuration purities as high as 94.5% of the more retained species in the extract and 98.9% of the less retained species in the raffinate were obtained.

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Simulated moving bed (SMB) chromatography has received significant attention in the last decade, particularly as regards the production of very valuable products, such as enantiomerically pure pharmaceutical compounds. Recent applications in the pharmaceutical industry use SMB systems containing a low total number chromatographic columns, usually four to eight. This paper deals with the modeling and simulation of SMB systems with only four, five and six columns. In particular, two modeling strategies, the equivalent true moving bed and the real SMB models, are compared for these units in terms of separation regions and system productivity. Also, the recently proposed Varicol process is analyzed and compared with the classical SMB operation, and the advantages of this new operation mode are shown for systems using a low number of columns. 