Page 281 - Chiral Separation Techniques

260 10 The Use of SMB for the Manufacture of Enantiopure Drug Substances: From …

Figure 10.2. Principle of the simulated moving bed (SMB), left: inlet and outlet lines are shifted
discontinuously; right: inlet and outlet lines are shifted simultaneously.

fixed with respect to the columns moves with respect to the zones and is alternatively
located in Zone IV, III, II and I. As the flowrates in the different zones are different,
the pump flowrate varies from cycle to cycle. It should be pointed out that this con-
straint is perfectly mastered and that this design is relatively simple and is used with
small differences on all the large-scale units.
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 dissym-
metry, 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 a different implementation (Fig. 10.3b), the recycling pump is fixed with
respect to the zones. It is always located between zones IV and I where no solutes
are present. In order to implement this idea, additional valves are needed, which
makes the system more complex than the previous one. Its main interest is found
when physical modulation is used, as in the supercritical fluid SMB, for which it can
be shown that a great interest could be taken from a higher pressure in zone I [56].
The only way to obtain this result is to maintain the recycling pump immediately
before zone I.
As illustrated in Fig. 10.3c, a final solution is to use the eluent pump instead of
the recycling pump. This implementation may enable the setup to be simplified, but
more valves are required than option a), and a drawback is that one outlet must be
recycled to the eluent tank.
Whichever, the retained design (type a, b, or c), there are always different options
to control the outlet flowrates. A pump, analog valve, and flowmeter or pressure