Description of the processSMB has been presented in many different ways in the scientific literature. Using a merry-go-round of 5–8 columns and a set of valves per column, a simple batch separation process can be converted into a continuous operation. This is achieved by changing the relative velocities of each compound in the columns. By "moving" the columns at a constant speed against the eluent flow, the most-retained component appears to move with the columns while the less-retained component flows with the eluent. As a result, a gap between the two fractions is created and can be filled continuously. To avoid accumulation, outlet streams must be collected on either side of the point of entry of the feed. This is truly a counter-current process and the packing material is used more efficiently. The only limitations are that SMB separations are conducted in an isocratic mode and that only two product streams can be isolated. This makes SMB an excellent candidate for binary separations such as the separation of enantiomers.
Method development and chiral applications
The number of drugs entering the market that have one or more chiral centers has grown significantly in the past decade. Knowing that one enantiomer can potentially carry side effects has brought regulatory authorities such as the US Food and Drug Administration to favor the single enantiomer version of a drug whenever possible. Specific crystallization, enzymatic or chemical resolution, or chromatography can be added as a unit operation to the existing synthesis route to obtain the single enantiomer. Or a completely new asymmetric route can be designed to obtain the desired single enantiomer. As a result, pharmaceutical companies have invested substantial resources in trying to find the right chiral catalyst or the right enzyme that will provide the single enantiomer at a satisfactory enantiomeric purity.
The development of a chromatographic chiral separation is a straightforward process that requires a few steps, described as follows.
Find a separation. There are a handful of chiral stationary phases (CSP) that provide greater than 80% probabilities of finding a good separation. If these phases are not working, there are a few more that may be suitable. The selection of solvents for the separation traditionally has been limited to acetonitrile, alcohols, and mixtures of alcohols with heptane. However, with the development of more robust CSPs that can handle solvents such as acetone, MTBE, toluene, and ethers, more possibilities exist. These solvents allow for high solubility and low viscosities, which are key elements to achieve high throughput. The screening process typically takes 1–2 weeks. From this study a handful of conditions can be identified as potential candidates.