Determination Of Adsorption Isotherm Of4-chlorobenzhydrol Enantiomers On Chiralpak AD Column And Its Simulation Study On Separation On Simulated Moving Bed Chromatography

4-chlorobenzhydrol is an important pharmaceutical intermediate for thesynthesis of two piperazine anti-allergic drugs. In practice, racemic4-chlorobenzhydrol is normally used to synthesis racemic products, which isthen separated to enentiomer medicals. This route, however, is notenvironmentally friendly due to the high consumption of raw materials andpollutions. In addition, S-4-chlorobenzhydrol is a necessary raw materialmedicine of Cloperastine Hydrochloride prescribed in Central antitussive.Production of single enantiomer of4-chlorobenzhydrol is, therefore, of greatenvironmental and commercial value.Due to the high separation efficiency, relatively low cost and reducedpollutions, the separation of chiral drugs on liquid chromatography has drawnmore and more attentions. More specifically, simulated moving bed （SMB）chromatography is a promising technique for chiral separation due to itscontinuous operation, stable product quality, low solvent consumption andability to achieve complete separation even for mixtures with low selectivity.The competitive adsorption isotherms of4-chlorobenzhydrol enantiomerson an amylose-based chiral stationary phase (Chiralpak AD) at25oC weredetermined in this study by the use of inverse method (IM). The equilibriumdispersive （ED）model was used to described the component mass balance inthe column. The fitting procedure adopts the non-dominated sorting geneticalgorithm (NSGA-II) and Levenberg-Marquardt algorithm (LMA). The fits toexperimentally measured overloaded band profiles of four typical isothermmodels were compared. The effects of column efficiencies and different samplesizes on fitting were investigated. It was found that using the Bi-Langmuirmodel with5parameters and simultaneously fitting three injection samples with different sizes gave the best prediction to independently measured band profiles.Triangle theory was used to find the completely separation regions for twodifferent racemic feed concentrations using the five-parameter Bi-Langmuirmodel and the obtained parameters. Effects of some key operating parameters,such as switching time and flowrates in different zones, on the SMBperformance in terms of purity and recovery were systematically investigatedby numerical simulations. Calculated temporal and spatial concentrationprofiles were provided to elucidate the separation mechanisms and effects ofoperating conditions.