Design and optimization of chromatographic processes in production scale

The production of chirality with maximum economy is one of the most challenging tasks of today's pharmaceutical industry. Apart from the use of inherent chirality (starting material from the chiral pool, e.g. amino acid derivatives, carbohydrates) the creation of chiral centers via biocatalysis or asymmetric synthesis are methods commonly used. A third way to obtain pure enantiomers is the separation of racemates via kinetic resolution through preferred crystallization or preparative chromatography on chiral stationary phases (CSP). This article will emphasize this last method and explain the possibilities of this technique especially in its application form as Simulated Moving Bed (SMB) chromatography and show its benefits and limitations. Therefore, comparisons to classical batch elution chromatographic processes as well as other unit operations (such as crystallization, etc.) have to take cost calculations into account. The performance of each separation process is quantified by three characteristic objective functions: productivity, dilution and solvent requirement. Lastly, the specific separation costs or the total costs of separation are calculated as an objective function to lay emphasis on the economy of the separation, including product recovery and solvent recycling. The comparison of these objective functions, which are determined for batch and SMB processes, leads finally to certain rules of consideration to decide what kind of process (either batch elution or SMB) is preferable as a function of the physical properties of the given binary mixture and the separation task.