Economics of chromatographic separations

Chromatographic separations are necessarily intermittent with alternate injections and elutions, although a measure of continuity can be achieved with an assembly of several units, or with suitably sized surge tanks. A process flowsketch appears in Figure 15.22(b). Information on production scale chromatography is provided by Conder (1973). Only separations difficult to achieve by other means are economical with chromatography. 

Such novel APIs are to be characterized with respect to, e.g. biotransformation, distribution, PK behaviour and other pharmacological properties. Elaboration of these data will require sensitive, selective and robust analytical methods most presumably based on LC-MS techniques. With respect to optimized economic feasibility procedures should be preferred that allow both (a) reduced consumption of organic solvents for sample preparation and chromatographic separation and (b) short run-time analysis. 

The advantages of egg yolk antibodies with respect to the welfare of animals and to scientific and economic considerations are described in a recent review.50 Although antibodies issued from this source are mostly used in laboratories and for diagnostics, they must be extracted and purified from very complex mixtures. The presence of massive amount of insoluble material and lipids is the most important problem. The collected egg yolk must first be clarified and the lipid removed for a consistent chromatographic separation. Table 3 summarizes the most important characteristics of expression systems for antibody preparation with regards to the chromatographic separation. 

In the chemical industry, chromatographic separation process is an emerging technology for the separation of pharmaceutical products, food and fine chemicals. To improve the economic viability, a continuous countercurrent operation is often desirable but the actual movement of the solid leads to a serious operating problem. Therefore, the simulated moving bed (SMB) process is an interesting alternative option. 

Chromatographic separations of the isotopic isomers of molecules are of interest first because they afford a convenient technique for analysis of mixtures, secondly because scale up in the future might afford economically feasible separations of macroscopic amounts of material, and finally because the values of the separation factors and their temperature coefficients are of intrinsic theoretical interest. This last follows because such data are straightforwardly related to the understanding of isotope effects on solution and adsorption processes and of the intermolecular forces which give rise to these effects. We have approached the general problem... 

The process described in the preceding subchapter may be considered obsolete as since the advent of industrial chromatographic separation, xylose can be obtained much more economically from sulfite waste liquor, which is an ideal starting material for the following... 

In production-scale processes economic pressure comes to the fore. Next to economic pressure it is very often not possible to separate the huge amounts involved with non-effective chromatographic separations. Although the time pressure is still present, an optimization of the chromatographic system with extensive studies is required. The investment in an optimized system will be repaid though by the reduced operation costs of a subsequent production process. 

The stability of all components of the chromatographic system must be assured for the complete operation time. The solvent must be chemically inert to all kinds of reaction. Neither an instable solvent, which for example tends to form peroxides, nor a solvent that reacts with the sample or the adsorbent is suitable for an economically successful solution of the separation problem. Of course, corrosion of the HPLC unit must be prevented, too. 

Whenever possible the development of a chromatographic separation should start with an isocratic elution mode. Its economic feasibility has to be checked afterwards. 

The time and money invested in model parameter determination has to be in balance with the aim of a certain chromatographic separation. Very often, only sample products are needed for further studies with the pure substances and, to evaluate a separation process, only a few milligrams of the feed mixture are available. Additionally, time is an important factor and quick and dirty /short-cut methods will be applied to find conservative operating parameter values for a safe separation. A quite different situation is the design of commercial large-scale production plants. Here process economics come to the fore. Therefore, precise parameters are necessary for process optimization. As some parameters may change during operation, repeated determination may be necessary to reestablish optimal production. 

Different authors have previously discussed the economics of preparative chromatographic separations [12-14], The main difficulty of the exercise is in the separation of the technical and the economic parameters. The influences of the various technical parameters of the process on the characteristics of the production performance are easy to figme out. They can be discussed in detail relatively independently of the specific details of a given separation problem. By contrast, the economic parameters are usually very specific to a product and even to the company that runs the separation and they are never constant over the long term. 

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