Continuous chromatography,moving

Pais L. S., Loureiro J. M., Rodrigues A. E. (1997b) Modeling, Simulation and Operation of a Simulated Moving Bed for Continuous Chromatographie Separation of l,l -bi-2-naphthol Enantiomers, J. Chromatogr. A 169 25-35. 

The concept of using continuous chromatography for the separation of stereoisomers or optical isomers is very old and was probably proposed for the first time by Martin and Kuhn in 1941 [28]. The suggested implementation was different from today s SMB technology, though the basic concept is the same. The chromatographic media is moved continuously in a conveyor belt, the feed is injected continuously at a fixed point, and the pure enantiomers are recovered at fixed points. In the idea of Martin and Kuhn, benefits were taken from the possibility of modulating the adsorption of the products at different temperatures. 

One to two spotted TLC plates are positioned in a TLC rack, and then placed in a unique developing chamber containing a very small amount of solvent. The solvent wicks up the TLC plate, over and past the spotted propellant samples and standards. Chemical components from each spotted sample and standard begin to separate (i.e., chromatography) moving up the plate, and continue to different heights on the TLC plate. 

At present, the purification by chromatographic processes is the most powerful high-resolution bioseparation technique for many different products from the laboratory to the industrial scale. In this context, continuous simulated moving bed (SMB) systems are of increasing interest for the purification of pharmaceuticals or specialty chemicals (racemic mixtures, proteins, organic acids, etc.).This is particularly due to the typical advantages of SMB-systems, such as reduction of solvent consumption, increase in productivity and purity obtained as well as in investment costs in comparison to conventional batch elution chromatography [1]. 

As the solvent begins to soak up the chromatography plate, it first dissolves the compounds in the spot that has been placed on the base line. The compounds present will then be carried up the chromatography plate as the solvent continues to move upwards. How fast the components of a mixture are carried up the plate is determined by (1) how soluble the component is in the solvent and (2) how much the component adheres to the stationary phase. An equilibrium is established in which the components partition themselves between the stationary phase and the mobile phase in a fixed ratio. 

One way to achieve this is to replace the column by a loop of three to six smaller columns, as shown in Figure 12.10c. This is the principle of multi-column continuous chromatography (MCC). Since only pure fractions are collected, leaving mixed fractions to re-circulate through the columns, there is no need to achieve a complete separahon. Inlet (eluent, feed) and outlet (extract-most retained component, raffinate-least retained component) streams are moved periodically by one column according to the direction of the liquid flow and following the concentration profile inside the column. 

Continuous processes are more efficient than batch processes, as the use of stationary phase is optimized and the amount of eluent needed for the purification is significantly reduced. The concentration of feed mixture inside the column can be much higher than it is in the case of a batch process. As a consequence, productivity is multiplied by a factor of two to five, less manpower is required, usage of stationary phase is optimized, and the amount of solvent used is reduced by a factor of two to ten. Two multicolumn continuous chromatography processes have been commercially implemented at commercial scale for pharmaceutical chiral separahons, these being the simulated moving bed (SMB) process and the Varicol process [15-17]. 

Szirmay, L. "Design Aspects of MAB (Moving Adsorbent Bed) Units for Continuous Chromatography-Like Sharp Separation," presented at the A.I.Ch.E. National Meeting, Orlando, FL, February 29, 1982. 

Continuous simulated moving-bed (SMB) chromatography technique (reviewed by Francotte [423]) may be the method of choice for production scale. 

Strube,J. Haumreisser, S. Schmidt-Traub, H. Schulte, M. Ditz, R., Comparison of Batch Elution and Continuous Simulated Moving Bed Chromatography. Org. Process Res. Dev. 1998,2,305. 

Pais, L., Loureiro, J., Rodrigues, A. Separation of l,l-bi-2-naphthol enantiomers by continuous chromatography in simulated moving bed, Chem. Eng. Sci., 1997a, 52, 245-257. 

In continuous chromatography the conventional stationary phase is moved countercurrent in a "moving bed" against the mobile phase. By adjusting the flow-rate of the bed and the mobile phase, one can enrich and separate a component or even a group of components in one direction or the other. 

Concerning its performance, steady-state recycling chromatography can be seen as an intermediate between simple batchwise or CLRC operation and continuous simulated moving bed (SMB) processes (Section 5.2). It combines lower complexity and equipment requirements than an SMB system with higher productivities and lower eluent consumption than obtained in batch chromatography. 

The Moving Bed Continuous Chromatography System Courtesy of Butterworths Scientific Publications Ltd. 

An interesting realization of continuous chromatography is simulated moving-bed (SMB) chromatography. Here, a serial connection of several chromatographic columns leads to a continuous simulated countercurrent process. In order to further explain the attribute simulated , first the idea of the true moving bed (TMB) is shown. 

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