Raffinate purities

The cyclic steady state SMB performance is characterized by four parameters purity, recovery, solvent consumption, and adsorbent productivity. Extract (raffinate) purity is the ratio between the concentration of the more retained component (less retained) and the total concentration of the two species in the extract (raffinate). The recovery is the amount of the target species obtained in the desired product stream per total amount of the same species fed into the system. Solvent consumption is the total amount of solvent used (in eluent and feed) per unit of racemic amount treated. Productivity is the amount of racemic mixture treated per volume of adsorbent bed and per unit of time. 

The equivalent TMB operating conditions and model parameters for the reference case were given in Table 9-1 and Fig. 9-9 presents the corresponding steady state internal concentration profdes obtained with the simulation package. The extract and raffinate purities were 97.6 % and 99.3 %, respectively the recoveries were 99.3 % and 97.6 % for the extract and raffinate streams. The solvent consumption was 1.19 L g and the productivity was 68.2 g/day - L of bed. 

A run was carried out with an extract flow rate of = 8.64 niL min (and a raffinate flow rate of = 4.72 niL min ). Raffinate purity close to 100 % (PUR = 99.6 %) was obtained, but the extract purity was lower (PUX = 97.5 %). The internal concentration profiles were evaluated at cyclic steady state (after 20 full cycles of continuous operation). Also evaluated were the average concentrations of both species in both extract and raffinate during a full cycle. 

A more serious limit to this implementation is due to the volume of the recycling pump and associated equipment such as flowmeters and pressure sensors. As the pump moves with respect to the zones, its volume leads to a dead volume dissymmetry, which can lead to a decrease extract and raffinate purities. This decrease can be significant for SMB with short columns and/or compounds with low retention. However, it can be easily overcome by using a shorter column or asynchronous shift of the inlets/outlets [54, 55]. This last solution is extremely efficient and does not induce extra costs because it is a purely software solution. 

In order to illustrate the critical process parameters of SMB process validation, we will consider the separation of the racemic drug as described in Process design. The study represents the effect of the influence of feed concentration, number of plates and retention factor on the second eluting enantiomer. The simulation of the process for different values of feed concentration is performed and the variations of the extract and raffinate purities are shown in Fig. 10.10. 

Figure 10.10 Influence of the feed concentration on extract and raffinate purity.

A second simulation study was performed to measure the effect on both extract and raffinate purities of a loss of chromatographic efficiency (Fig. 10.11). 

Figure 10.12. Influence of retention factor of the more retained compound on extract and raffinate purity. Solid line without adjustment of the operating flow rates dotted lines with adjustment of the operating flow rates.

This type of approach has been described by Lorenz [23], who demonstrated the potential for improving MCC throughput by coupling crystallization to the MCC separation. In the case of radafaxine it was established that there is a eutectic at 0.85 (see Figure 10.5) and mixtures > than this value result in crystallization of pure (S,S)-enantiomer. For example, if an initially lower raffinate purity (-95%) is obtained from the MCC and this is followed by crystallization during isolation it is possible to obtain material that is 99.5% pure. 

The steady state of a TMB is calculated for different numbers of theoretical plates, where an identical number of plates in each zone is assumed. The extract and raffinate purities are derived from each numerical simulation. 

TABLE 7 Influence of the Equivalent Number of the TMB on the Extract and Raffinate Purities... 

This set of flow rates is then used in a model solving the set of Eq. (19) to get the internal profiles and thus the extract and raffinate purities. 

Another test was performed on the pilot plant after increasing the recycling flow rate from 7.76 to 8.35 liters/h. The results presented in Fig. 15 show now well positioned profiles, the extract and raffinate purities are respectively 96.3 and 95.5%. 

The step responses of the extract and raffinate purities, resp. yj and (Fig. 2) are obtained for 0.05% steps of respective eluent, recycle, extract and solid flow rates,resp. M , 2, U and U4, used as manipulated inputs. The steps are performed after the process reaches a steady state purity of 95% for both products. Most of the responses are close to first order step responses and present similar time constants, which is suitable for further control. Only the step response of the extract purity with respect to the eluent... 

Figure 2 Step response coefficients of the extract and raffinate purities with respect to the flow rates (from top to bottom eluent, recycle, extract and solid ).

Figure 4 Flow rate control in case of raffinate purity tracking. Left controlled outputs. Right manipulated inputs.

When a higher C4 raffinate purity is required it is possible to perform a more efficient removal of oxygenates (mainly DEE) by including an additional distillation tower or an oxygen removal unit (ORU) based on molecular sieves. 

With more than one contact, an operating point Q is located outside the ternary diagram, as shown in Fig. 10. With a specified solvent/feed ratio and a desired raffinate purity,, with the given feed, Xp the composition of the final extract, Y , is fixed by material balance. Point Q is formed by the intersection of the line drawn from Y through Xp, with the line drawn from the fresh solvent 5 through. ... 

Even when the two limitations of immiscibility and constant distribution coefficient do not quite hold. Fig. 11 does allow a quick estimate of the trade-offs between solvent/feed ratio and number of stages required to obtain a desired degree of extraction (raffinate purity). 

If, for instance, as in our example, the purity of the extract stream is too low while the adsorption front of component A is still far from stopping point 3, the operating point has to be varied along one isofeed line. In this case, ntn and mm and, therefore, also the flow rates in sections II and III are increased by the same amount. This can be done by decreasing the extract flow rate and increasing the raffinate flow rate while the feed rate is held constant. When both the extract and the raffinate purity are higher than required, or the concentration profile can still be... 

Columns/zone Extract purity (%) Raffinate purity (%) Increase in productivity (%) Decrease in eluent (%)... 

The simplest case may be formulated for systems with linear adsorption isotherms using the equilibrium theory. The region of complete separation (100% extract and raffinate purity) predicted by the equilibrium theory is a triangle shown... 

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