Simulated Moving Bed Chromatography Offers Real Attractions

A continuous purification technique, simulated moving bed chromatography combines high yields and purities with easy scale up and reasonable throughputs.

By Kathleen Mihlbachler, Eli Lilly and Company, and Olivier Dapremont, Aerojet Fine Chemicals

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SMB also can handle more complex separation such as purification of proteins. However, some modifications to the standard unit design are necessary to allow for packing regeneration [7].
As SMB technology becomes more widespread, a larger variety of applications undoubtedly will be developed and publicized.

Real potential
The pharmaceutical industry is investigating SMB as a production tool, attracted by its fast method development and easy scale up. A few roadblocks still exist but they are fading away as more and more units find their way into both industry and universities. Contract manufacturing companies now use SMB units at different scale and major pharmaceutical companies are installing their own production units. As the technology evolves, such systems will become more of a routine unit operation rather than the “niche technology” of a few experts.


Dr. Kathleen Mihlbachler is research scientist in MS&T for Eli Lilly and Company, Indianapolis, Ind. E-mail her at mihlbachlerka@lilly.com.

Dr. Olivier Dapremont is director, chromatographic separations, for Aerojet Fine Chemicals, Rancho Cordova, Calif. E-mail him at
Olivier.Dapremont@aerojet.com.

REFERENCES
1.  Miller, L., C. Orihuela, R. Fronek, D. Honda and O. Dapremont, “Chromatographic resolution of the enantiomers of a pharmaceutical intermediate from the milligram to the kilogram scale,” J. of Chromatogr. A, 849, Issue 2, p. 309 (1999).
2. Seidel-Morgenstern, A., “Experimental determination of single solute and competitive adsorption isotherms,” J. of Chromatogr. A, 1,037, Issues 1-2, p. 255 (2004).
3. Ruthven, D.M. and C.B. Ching, “Counter-current and simulated moving bed adsorption separation processes,” Chem. Eng. Sci., 44, p. 1,011 (1989).
4. Storti, G., M. Mazotti, M. Morbidelli and S. Carra, “Robust design of binary countercurrent adsorption separation processes,” A.I.Ch.E. J., 39, p. 471 (1993).
5. Mihlbachler, K., A. Jupke, A. Seidel-Morgenstern, H. Schmidt-Traub and G. Guiochon, “Effect of the homogeneity of the column set on the performance of a simulated moving bed unit. Part II: experimental study,” J. of Chromatogr. A, 944, p. 3 (2002).
6. Metz, P. and O. Dapremont, “SMB takes on Paclitaxel,” Pharma. Mfg., 3, Issue 9, p. 27 (Nov/Dec 2004).
7. Xie, Y., S. Mun, J.-H. Kim and N.-H.L. Wang, “Standing wave design and experimental validation of a tandem simulated moving bed process for insulin purification,” Biotech. Prog., 18, p. 1,332 (2002).
8. Mihlbachler, K., “Enantioseparation via SMB chromatography: a study of Tr<umlaut>öger’s base unique adsorption behavior and the influence of heterogeneity of the column set on the performance of the SMB process,” Logos-Verlag, Berlin (2002).

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