Chromatography, preparative scale

Preparative chromatography has been used for chiral separations for years, but examples of multi-kg separations (and hence larger ones) were rare until recently. The development of SMB techniques (both hardware and simulation software) has made major breakthroughs in this field. The ability of SMB as a development tool has allowed the pharmaceutical manufacturer to obtain kilo grams quantities of enantiopure drug substances as well benefit from the economics of large-scale production. 

These ideas and methods of preparative selective up-scale chromatography suggest that the use of new types of biosorbents and, in particular cellosorbents, and the application of theoretically based conditions for stepwise desorption of the components is an important new approach to preparative chromatography. 

Column chromatography (CC) can be used at laboratory, pilot-plant, and commercial-plant scales. Preparative chromatography has been utilized for the purification of many fine and even bulk chemicals. 

In preparative chromatography, selectivity and efficiency no longer have the same importance they do in analytical chromatography. A certain selectivity is required in preparative chromatography as everywhere else in order to achieve the separation, but other parameters are at least as important if not more so. These include the loading capacity of the stationary phase and the maximum speed (throughput) of the process. The three main economic criteria for a large scale separation process are... 

A second field of rapid development in the l.c. of carbohydrates is in practical, preparative chromatography. Early preparative systems used large, expensive columns with low resolving power, and hence, were not extensively applied in carbohydrate research. New research is showing that various carbohydrates can be separated on the gram scale, using normal l.c. equipment and large columns home-packed with relatively... 

The nonlinear nature of preparative chromatography complicates the separation process so much that the derivation of general conclusions regarding either the scaling up or the optimization is a rather difficult task. The optimization of preparative chromatography is further complicated by the fact that the choice of the objective functions in preparative chromatography is not as simple as in... 

In preparative chromatography, the information provided by the isotherms and by the proper model of chromatography will help the scale-up and optimization of batch and continuous purifications with minimum use of solvents and sample. Although it is rather difficult to give straightforward instructions how to optimize a preparative separation, some general guidelines are provided in this chapter. 

A. Felinger, in Scale-Up and Optimization in Preparative Chromatography, A.S. Rathore, A. Velayudhan (Eds.), Chapter 3, Marcel Dekker, New York, 2002. 

Preparative chromatography, which is used on a large scale for the separation and purification of components of a mixture, has progressed into a stand-alone analytical technique with impressive performance, and is now used for microseparation. 

Scale-Up and Optimization in Preparative Chromatography Principles and Biopharmaceutical Applications, edited by Anurag S. Rathore and Ajoy Velayudhan... 

Analytical methods can be transferred easily to the preparative scale in polysaccharide-based CSPs, and these compounds have been used in preparative chromatography. Cellulose triacetate, which has good loading capacity, has been used for preparative separation at the industrial scale [70,85]. Moreover, the low cost of cellulose triacetate synthesis makes CTA ideal for preparative chromatography. 

In addition to requiring significant bulk material, the timeframe to complete the isolation is considerable. If the maximum analytical load for a 4.6 mm x 150 mm column has been determined to be 5 mg, assuming the isolation will be performed using semi-preparative chromatography (20 mm x 300 mm column), approximately 190 mg of sample can be loaded onto the preparative column. For a 0.1% level unknown, this translates to 190 pg of unknown injected onto the preparative column. Therefore, a total of 27 injections are required. If the assay time were estimated to be 1 hr, it would take at least 27 hr to perform the injections needed to obtain 5 mg (once again assuming 100% recovery). This timeframe does not include the time needed for method scale-up development, concentration and... 

Since preparative chromatography is the single most widely used unit operation for process-scale purification of biologicals, the development of... 

Preparative chromatography has achieved a unique position in the purification of biotechnology products on an industrial scale. As an increasing number of biotechnology products are approved by the Food and Drug Administration (FDA) and with the rapid increases in the scales at which these products are produced, there is a growing need for the design of downstream processes with fewer, more efficient steps. While elution chro-... 

---