SMB modifications for increased throughput.
SMB provides a significant advantage over batch chromatography when the selectivity of the separation is rather low. In
the case of high selectivity, batch chromatography may outperform SMB because of flow and operating pressure constraints.
In an SMB unit, the flow rate in the first zone of columns pushes out the most retained product. For a long retention time,
it takes a high flow rate to push everything out of the column before the column switch occurs. Because all the zones of the
SMB are connected, if one zone is operated at a very high flow rate, then the other zones must be operated at a lower flow
rate. This zone manipulation is necessary to manage operations below the maximum operating pressure of the system. As a result,
the production rate is reduced. AFC developed a simple modification to the process (see Figure 3) that alleviates the pressure
constraint by decoupling the first zone of the SMB from the other zones of the SMB unit (12). This additional zone allows
for a rapid wash of the column with the mobile phase at maximum operating pressure without affecting the pressure in the other
zone. As a result, the rest of the separation can be conducted at a higher flow rate and therefore at a higher throughput.
Figure 3: Comparison between traditional four-zone simulated moving-bed (SMB) and the modified SMB system for separations
with large selectivity or increasing retention time. (FIGURE IS COURTESY OF THE AUTHOR)
SMB for chiral separations and impurity removal.
Ideally, racemic feeds only contain the two enantiomers. Unfortunately, in most cases, a few impurities that are closely
related to the product also are present in the mixture. These impurities are usually either leftover starting material or
side products from previous reactions. In either case, they might be difficult to remove during downstream processing without
sacrificing yield. The chiral SMB separation can potentially be used to purify the product as the enantiomers are separated.
Many publications describe the SMB process, but they rarely address impurities (6, 7, 13). If an impurity is present in the
racemic product, it can potentially be doubled after the separation because approximately 50% of the mass of the feed is removed.
Therefore, it is important to know the fate of the impurity during the SMB separation.