Frédéric Charton

Complete design of a simulated moving bed

Abstract The operating conditions of a simulated moving bed working under conditions of non-linear chromatography are difficult to find experimentally. A design procedure based on the modelling of multi-component chromatography is described. This rigorous and general procedure can be applied provided that basic data characterizing the experimental system are available. Even if the main parameters to be set are the flow-rates (one internal flow-rate and three out of four inlet/outlet flow-rates), it is explained how other free working parameters can be chosen. Special attention is paid to the column length, mobile phase velocity and particle size. It is shown how strongly they can influence the performance of a simulated moving bed.

Determination of binary competitive equilibrium isotherms from the individual chromatographic band profiles

A numerical solution of the inverse problem of nonlinear chromatography is described and validated. This method allows the determination of best numerical estimates of the coefficients of an isotherm model from the individual elution profiles of the two components of a binary mixture. The sample size must be large enough for the two bands to interfere strongly and for their maximum concentrations to exceed the range within which the isotherm equation is needed. In two cases, excellent agreement was observed between the equilibrium isotherm equations obtained by this new method and those determined by the classical combination of elution by characteristic points and binary frontal analysis. In the first case, the adsorption of the ketoprofen enantiomers on a cellulose-based chiral phase is accounted for by a competitive Bilangmuir isotherm. In the second case, the adsorption of benzyl alcohol and 2-phenylethanol on C18 silica is accounted for by a competitive Langmuir model. The importance of using the proper boundary conditions (i.e., a realistic injection profile) is stressed. The new method seems especially well suited for the rapid determination of the isotherms of enantiomers needed for the computer-assisted optimization of the separation of mixtures of these compounds, e.g., in simulated moving-bed applications.

Recycling in preparative liquid chromatography

Abstract A comparison is made between the performance achieved in preparative chromatography when using elution, the most usual operating mode of this technique, and the different implementations of recycling. This work is based on the experimental results obtained in the separation of the enantiomers of ketoprofen on a cellulose-based stationary phase, using the various Chromatographic modes. It uses also the modeling of non-linear chromatography to compare the different operating modes considered. Theoretical and experimental results are presented and compared. In some cases, it is possible to achieve simultaneously both an increase in the production rate and a decrease in the amount of eluent needed.

Comparison of the specific productivity of different chiral stationary phases used for simulated moving-bed chromatography

Abstract The use of preparative chromatography for the separation of enantiomers is now a well established technique. With the technical setup of simulated moving bed-chromatography significant improvements can be achieved regarding throughput and eluent consumption. To find the optimum separation system, the determination of some parameters with analytical chromatographic methods is sufficient. This article gives a procedure to optimize the separation conditions for a precursor of the novel Ca-sensitizing drug (EMD 53998) on four different chiral stationary phases. This analytical procedure led to a maximum specific productivity for the desired enantiomer of 430 g enantiomer/d·kg chiral stationary phase.

Modeling of the adsorption behavior and the chromatographic band profiles of enantiomers: Behavior of methyl mandelate on immobilized cellulose

Abstract The adsorption isotherms of (−)- and (+)-methyl mandelate from a hexane-isopropanol (90:10) solution were measured on a chromatographic column packed with 4-methylcellulose tribenzoate coated on silica. These isotherms are accounted for by a bi-Langmuir isotherm model, the two Langmuir terms having widely different initial slopes and saturation capacities, but each term having the same saturation capacity for the two enantiomers. The competitive isotherms were also measured. They are in excellent agreement with the prediction of a competitive bi-Langmuir model based on the single-component isotherms. The individual band profiles are in agreement with the profiles calculated from these isotherms. Thus, a simplified competitive isotherm can be used to model a separation on a chiral stationary phase the recognition mechanism of which is not well identified and the adsorption behavior of which is certainly not ideal.