Eluent consumption

In opposition to the usual (elution) chromatography, SMB is a continuous process, and is thus much more adapted to large-scale production. Moreover, SMB is based on a countercurrent contact between the liquid and the adsorbent, which leads to lower eluent consumption. 

Optimum flowrates, resulting in high productivity and low eluent consumption, are estimated first for an ideal system , which means that kinetic and hydrodynamic dispersive effects are assumed to be negligible [46]. This procedure has recently been improved [57]. 

The optimum of the complete triangular separation region (maximizing productivity and minimizing eluent consumption) is the point w corresponding to ... 

Finally, simulation studies were performed to evaluate the influence of change in eluent consumption or variations due to different lots of CSPs on the retention of the second peak. The variation in retention of the second peak is another critical parameter on resulting purity of the extract and raffinate. 

The graph in Fig. 10.12 shows that the purity decreases very quickly below acceptable levels as retention factor of the more retained enantiomer decreases. Flowever, with minor adjustment of the SMB internal flow rates, a variation of more than 10 % of the retention factor of the more retained enantiomer still meets required purity, productivity, and eluent consumption. Control of critical parameters such as retention factors can be made without modification of the feed and eluent flowrates. 

Eluent consumption, since this determines the cost for mobile phase in terms of preparation and handling (tanks, water preparing systems, pumps)... 

The performance of HPLC separations can be increased not only by the application of two- or multidimensional techniques but also by the use of simulated moving bed (SMB) [100-102] or true moving bed (TMB) techniques [103,104], SMB is a multicolumn separation technique allowing the continuous separation of analyses with higher productivity and smaller eluent consumption than the traditional single-column procedures. TMB... 

An added benefit of the mixed IPA/acetonitrile solvent system is that the race-mate 2 was more soluble in this medium, with the overall result that the productivity doubled to a maximum of -4,6 kg racemate per kg of CSP per day with eluent consumption decreasing to 270 L/day. Furthermore, the findings described above of combining crystallization with the chromatography could also be applied to this eluent combination. 

For a preparahve applicahon, focus is on recovering the targeted products while ophmizing produchon costs. The object of the separation is to reach the purity and recovery yield required for one or more specific components of the feed mixture. To maximize produchon, injechons are made as often as possible. The amount of stahonary phase used is set in order to minimize the costs of the product, equipment, and eluent consumption. Figure 12.2 presents the preparahve chromatogram of the same compounds as in Figure 12.1, where the injected amount is maximized in order to ophmize the process [5]. 

Batch processing appears as one of the simplest ways to use chromatography. This process uses one column and operates in a succession of injections (at the inlet of the column) and collections (at the outlet of the column). The eluent consumption is the ratio of the volume of eluent used divided by the amount of product purified. Reduction of the eluent consumption can be achieved by, for example, increasing the injected amount or reducing the cycle time [12]. 

Reducing Cycle Time with Stacked Injections (Case of Isocratic Eluents) For chromatographic separations performed using isocratic eluents (i.e., whose composition does not change over time), once the injected amount has been increased to its ophmal value, eluent consumption can then be reduced by stacking... 

The first approach to reducing eluent consumption presented above was the optimization of chromatographic processes to reduce the amount of solvent used to... 

The final approach to the reduction of eluent consumption is the optimal recycling of solvents. Indeed, preparative and industrial chromatography can be designed as a unit operation that includes solvent recycling dry feed mixture is injected while dry separated compounds are recovered. Many techniques can be applied depending on the situation in isocratic (that is with a constant mobile phase composition) or gradient conditions, and with organic and/or supercritical eluents. 

The process daily throughput is linked to both the injected amount per run and the time between two successive injections. This time has to be minimized using stacked injections in order to optimize the process productivity and further decrease the eluent consumption. Minimum time between two successive injections corresponds to the time needed for eluting the two enantiomer peaks. Under the selected conditions, this time was equal to 100 s. 

Nevertheless, CEC is still an attractive technique, because of low eluent consumption and small sample size requirements. It offers the advantage over LC of greatly increased plate counts and therefore the possibility of resolving closely related analytes not separable by LC. It is the least mature of the CE modes, but there is much interest in future development of CEC. 

Presently, there is considerable interest in the preparative applications of liquid chromatography, even though it is often considered expensive. To make the chromatographic process more attractive, attention is focused on the choice of the operating mode in an effort to minimize eluent consumption and to maximize productivity, which is of key importance when expensive packings are used. Among the alternatives to the classical process (elution chromatography), much attention is paid to SMB. 

The simplest SMB system is made of three zones, for which zone number IV does not exist, and the flux exiting zone III is sent to concentration unit. The three-zone SMB process (Fig. 3) is an economical alternative to the four-zone system when the eluent consumption is not an important concern and/or when the raffinate is a zero- or low-value by-product. 

In conclusion, the four-zone SMB process scheme is generally the best choice and must be investigated first for binary separations. In several instances, however, alternative schemes offer a better technical solution. The three-zone SMB should be considered when the eluent consumption is not a limiting factor. The five-zone SMB is interesting for multicomponent separation or when an extreme purity of one of the two effluents is wished with a maximum unit throughput. 

The feed concentration has a strong influence on the SMB performance and must be well chosen. The productivity and the eluent consumption are two main economic criteria involved in chromatographic processes.30 Their variations versus the feed concentrations can be checked in order to choose an appropriate feed composition. This study can be quickly carried out for an ideal TMB, as mentioned in the previous section. It has been reported14 that the productivity increases and the eluent consumption decreases when the feed concentration increases The variations are usually rather steep in the low concentration range and very smooth in the high concentration range. As a consequence, low injection concentrations will have to be avoided. However, even if achievable, very high concentrations will not be suitable because... 

A comparison of the batch and the SMB modes proved to greatly favor SMB The productivity and the eluent consumption was improved by three at least times using SMB. 

Simulated moving beds have been successfully used during almost 30 years at a very large scale in petrochemistry. It appears clearly that this technology has a great potential for fine chemistry and the pharmaceutical industry. More and more applications are described for the biochemical field (leading sometimes to 10 times lower eluent consumption compared to the usual chromatography). Because small-scale units are already available, SMBs can... 

If elution and frontal chromatography are still the main implementations used in preparative processes because of the simplicity of their development, processes like true moving bed (TMB) or simulated moving bed (SMB) have been used for about 40 years in large scale separations in petroleum or sugar industries [1,2]. In these processes, a countercurrent between solid and fluid phase is realized (or simulated) in order to improve process productivities and to decrease the eluent consumption. These implementations are now developed for laboratory and small productions and find a lot of applications in pharmaceutical and fine chemistry industries [3,4],... 

It can be shown that the performances of simulated moving beds are equivalent to those of true moving beds [11]. Also, SMB process has a lot of advantages compared to classical elution chromatography. With a continuous process, purified products are recovered at 100% with a low dilution and a low eluent consumption. Moreover, SMB process are not very sensitive to column efficiency and we can obtain very good product purities with even low column efficiencies [11],... 

The purpose of zone 1 is to stabilize the concentration front of component B in order to prevent B to be sent in zone 4 in the solid phase direction. The use of a high pressure in this zone allow increase the elution strength of the eluent and to decrease the flowrate in zone 1 leading to reduce eluent consumption and to increase the concentration of the extract flowrate. 

In all cases, using 5 colinnns, the optimal column configurations are found to be 1/2/1/1 and 1/1/1/2—I/I/2/1-1/1/2/1—1/2/1/1 for the SMB and 4 subinterval Varicol unit, respectively. It can be observed that for fixed purity specifications, both the SMB and the Varicol processes require to increase the eluent consumption in order to increase the feed flow rate. Secondly, the Varicol process consumes less eluent, D than the SMB process for the same feed flow rate, F or equivalently for the same eluent consumption, D, the Varicol process can treat more feed, F. However, the extent of improvement depends on the purity specifications. The more stringent the purity requirement, the larger the improvement achieved by Varicol over SMB. For example, at D = 5.6 ml/min, the improvement in production rate, F of Varicol over SMB is 10%, 25% and 127% for a purity requirement both in the extract and in the raffinate streams of 90%, 95% and 99%, respectively. Finally, it is seen from Figure 3 (for the case of purity requirement of 95%)... 

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