(134e) Separation of Fine Chemical Species by Means of Continuous Chromatography: The Simulated Moving Bed Technology

The use of continuous chromatographic counter current operation maximizes the mass transfer driving force, providing a better utilization of the adsorbent, which may have a rather low selectivity. In addition, some typical advantages of continuous configurations include reduction of solvent consumption, increase productivity and purity and less diluted product streams, when compared to conventional batch chromatography. By means of moving bed operating mode it is possible to achieve high purity even if the resolution of the two peaks is not excellent. This is contrary to batch chromatography where high resolution is vital in order to achieve high purity. The actual circulation of the solid phase inside the column and the consequent recycle presents some technical problems, namely: equipment abrasion, mechanical erosion of adsorbent, difficulties in maintaining plug flow for the solid. This clearly limits the implementation of such technologies. In order to avoid this issue, a sequence of fixed bed columns was conceived (Broughton and Gerhold [1]) in which the solid phase doesn't move in relation to a fixed referential, but the relative movement between both fluid and solid streams is created by switching all the inlet and outlet fluid streams from time to time in the direction of the fluid flow. In the simplest operating mode, the period that a certain operating configuration prevails is called the switching time. Since the solid flow is simulated by the ports shift as described above, this technology is called Simulated Moving Bed (SMB). In the last years some “non-conventional” SMB operating modes, such as asynchronous port movement and variable inlet or outlet flow rates, were proposed providing more flexibility in the design and more efficient units.

Industrially, SMB applications can be regarded as “Old” and “New” applications associated with petrochemical and pharmaceutical/fine chemistry fields, respectively, as reviewed by Sá Gomes et al, 2006 [2]. Among the first applications of this technology (back to 1960s) is the Parex® unit (UOP) for separation of para-xylene from mixtures with the C8-isomers. In the last decade, particularly in the area of drug development, the advent of SMB has provided a high throughput, high yield, solvent efficient, safe and cost effective process option. Although it had long been established as a viable, practical, and cost-effective liquid-phase adsorptive separation technique, the pharmaceutical and biomolecule separations community did not show considerable interest in SMB technology until the mid-1990s. In 1992, Daicel Chemical Industries, Ltd. first published the resolution of optical isomers through SMB. Since that time, a considerable number of articles, patents and books on the application of SMB to pharmaceutically important compounds have been published, and already approved by FDA for some API production.

The objective of this work is to present an updated review of all SMB applications to the pharmaceutical industry, with particular emphasis on the work developed in LSRE concerning the SMB application to pharmaceutical and fine chemical separations, since the early 90's to 2007 with the design and construction of a flexible SMB unit (FlexSMB-LSRE®).

1.Broughton, D.B., C.G. Gerhold, (1961) Continuous Sorption Process Employing Fixed Bed of Sorbent and Moving Inlets and Outlets. US patent no 2 985 589

2.Sá Gomes, P.; Minceva, M.; Rodrigues A. E.; (2006) Simulated Moving Bed: Old and New, Adsorption, 12:375-392.