Varicol process

Continuous processes are more efficient than batch processes, as the use of stationary phase is optimized and the amount of eluent needed for the purification is significantly reduced. The concentration of feed mixture inside the column can be much higher than it is in the case of a batch process. As a consequence, productivity is multiplied by a factor of two to five, less manpower is required, usage of stationary phase is optimized, and the amount of solvent used is reduced by a factor of two to ten. Two multicolumn continuous chromatography processes have been commercially implemented at commercial scale for pharmaceutical chiral separahons, these being the simulated moving bed (SMB) process and the Varicol process [15-17]. 

In both the SMB and the Varicol processes, the columns are distributed between four zones, as shown in Figure 12.11 ... 

In the Varicol process, hnes are shifted asynchronously. In this case, the column distribution between zones does not stay the same during the period, because lines are shifted at different times, so that the allocation changes accordingly. Since the number of columns in one zone is not constant over a period of time, the configuration of columns contains non-integral numbers. For example, a configuration of O.5/1.5/1.5/O.5 in a 4 column system is possible. A Varicol process is more adaptable than an SMB one as more flexible options are available for the repartition of columns. It is commonly observed that Varicol is 15-25% more productive than SMB (typically 5 or 6 columns are used in Varicol , whereas 6 to 8 columns are used in SMB) [11, 18]. 

Z. Zhang, M. Mazzotti, M. Morbidelli, Multiobjective optimization of simulated moving bed and Varicol processes using a genetic algorithm. 

Table 1. Optimization results of SMB and Varicol processes for various values of Ned...

Figure 2. Optimal solutions for the SMB and Varicol processes with 90%, 95% and 99% purity requirements.

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%)... 

Zhang Z., Hidajat K., Ray A.K. and Morbidelli M., Multiobjective optimization of simulated moving bed system and Varicol process for chiral separation, AIChE J. (2002) in press. 

Ludemann-Hombourger O., Nicoud R.M. and Bailly M., The Varicol process a new multicolumn continuous chromatographic process, Sep. Sci. Technol. 35 (2000) pp. 1829-1862. 

Another objective function for process optimization is the eluent consumption, which is not considered here because of the fixed flow rates in the regeneration sections. A further promising alternative for process optimization is the VariCol process proposed by Ludemann-Hombourger et al. (2000b) (Chapter 5.3.5.1). This process is based on an asynchronous movement of the in- and outlet valves and offers, therefore, the opportunity to apparently decrease the number of columns, with constant purity and the same amount of product. This concept can be applied for all of the processes considered here. 

Ludemann-Hombourger, O., Pigorini, G., Nicoud, R.M., Ross, D., Terfloth G. Application of the VARICOL process to the separation of the isomers of the SB-553261 racemate,... 

Toumi, A., Engell, S., Ludemann-Hombourger, O., Nicoud, R. M., Bailly, M. Optimization of simulated moving bed and VARICOL processes, J. Chromatogr. A, 2003, 1006, 15-31. 

The principle of the Varicol process consists in a non-synchronous shift of the inlet and outlet ports of a multi-column system on a recycle loop [70]. The Varicol process is characterized by a even more efficient use of the stationary phase than the one achieved in the SMB process. 

Both TMB and SMB include four zones that are unchanged during operation. Both the SMB and the Varicol processes consist in a series of columns that are connected in series, with inlet/outlet lines connected between the columns. In the conventional SMB process all these inlet/outlet lines are shifted periodically and simultaneously. This switching insures that all the inlet (feed and desorbent) and outlet (extract and raffinate) ports are all switched in the same time in the direction of the liquid flow. Accordingly, the number of coliunns in each zone stays the same at each moment. 

In the Varicol process, there are also four column zones, but the inlet and outlet lines are no longer shifted simultaneously. In other words, the column distribution between the four zones varies during a cycle. Like the conventional SMB process, the Varicol process is periodic. It returns to the same status at the end... 

In the Varicol process, the two outlet lines between each column must be connected to the recycling line before the eluent and the feed Hnes are shifted in the direction of the fluid stream. This modification to the conventional design prevents the feed flux from polluting the extract or the raffinate streams when the number of columns in zone II or III, respectively, falls temporarily to zero. This also prevents the eluent flux from diluting the extract or the raffinate flux when the number of columns becomes equal to zero in zones I or IV. 

These results show that both the Powerfeed and the Varicol processes provide a performance that is significantly improved compared to that of the conventional SMB process, and that the extent of the improvement achieved is larger for more difficult separations. A rigorous comparison between the Varicol and the Power-feed processes in general terms is not possible, but it seems fair to say that they are equivalent in terms of potential performance, although the implementation of the Varicol process may be simpler than that of the Powerfeed process. 

Multiobjective optimization of the SMB and Varicol processes by a non-dominated sorting genetic algorithm (NSGA) which does not require any initial guess of the optimum solution was carried out by Zhang et al. [80] who used in that process an objective function that maximizes the feed flow rate (maximum throughput). 

For the 4-subinterval 5-column Varicol process, the optimum is foimd along line FGLM. The multiobjective optimization effectively shows the variability of the decision variables and operation conditions of the continuous chromatographic separation. The 5-column Varicol process offers higher purities than the equivalent 5-column conventional SMB, using the same amount of stationary phase. 

The Varicol process was found to be superior to the corresponding SMB when 40 pm or 30 pm particles were used. For the same production rate, Varicol can give a higher extract purity. In the case of 20 pm particles, however, the Varicol could not outperform the SMB process. The performance difference of the two processes diminishes as the particle size decreases and it disappears at 20 pm in that particular instance [81]. 

Simulated moving bed (SMB) and Varicol processes Simultaneous maximization of the purity of the extract and productivity of the unit. Genetic algorithm SMB and Varicol processes for a model chiral separation were optimized for multiple objectives and their comparative performance was discussed. Zhang et al. (2003)... 

Glucose-Fructose separation using SMB and Varicol Processes Two cases (a) maximization of both purity and productivity of fructose, and (b) maximization of productivity of both glucose and fructose. NSGA Both operation and design optimization were studied. This is one of the three applications presented in Yu et ol. (2004). Subramani et d. (2003a) Yu et d. (2004)... 

Recovery of p-xylene from a mixtnre of Cg aromatics using SMB-based Parex process Several cases of (a) maximization of recovery of p-xylene and minimization of desorbent consnmption, and (b) maximization of both pnrity and recovery of p-xylene. NSGA-n-JG Varicol process was also optimized and compared with the Parex process. Knmp et al. (2005b)... 

Enantioseparation of SB-553261 racemate using SMB technology Three cases (a) maximizing the purity and productivity of raffirrate stream, (b) maximization of purity and productivity of extract stream, and (c) maximization of feed flow rate and minimization of desorbent flow rate. NSGA-n-JG Both SMB and Varicol processes were optimized, and the study found that the latter has superior performance. Wongsoc/fll. (2004)... 

Subramani, H. J., Hidajat, K. and Ray, A. K. (2003a). Optimization of simulated moving bed Varicol processes for glucose-fructose separation, Trans IChemE., 81, pp. 549-567. 

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