In this work we report a class of simple SMB schemes, using only two and three columns, to achieve both binary and ternary separations. These schemes have the advantage of employing fewer columns, and requiring only two or three pumps, which renders the system more economic; the set-up is also simpler to build.

However, these compact SMB schemes expand the degrees of freedom for operating the cycle, which renders them more sensitive to disturbances, namely flow-rate stability and parameter uncertainty. Therefore, a robust design of the system is needed.

A robust design of the proposed two- and three-column processes has been developed for protection from flow-rate, dead-volume, and isotherm uncertainties. The optimal cycle parameters are chosen only among candidate solutions that are robust feasible. This gives rise to a robust approach to optimal design in which the nominal problem is replaced by a worst case problem. The nominal optimization problem and its robust counterpart are formulated using a full-discretization approach for steady periodic dynamics. The resulting nonlinear programming problems are solved by an efficient interior-point solver.

The procedure is successfully employed to find robust operating conditions for the linear separation of nucleosides mixtures by reversed-phase and quiral resolution of a racemic antidepressive NRI drug. The robust schemes are validated experimentally. Emphasis is given to the pros and cons of running the processes under nominal and robust operating conditions.