(48e) Optimization Of Steady-State Recycling Chromatography Under Reduced Purity Constraints

Simulated moving-bed chromatography (SMB) has become an industry standard for binary chromatographic separations. As has been demonstrated in multiple difficult separations, the SMB method usually offers lower solvent consumption and often higher productivity than batch elution chromatography. On the other hand, recently interesting alternatives have been proposed based on single-column schemes with recycling (for example, one-column SMB anologs and steady state recycling). Due to their technological simplicity, such processes allow for lower high investment costs and higher versatility than SMB units.

Steady-state recycling chromatography (SSR) is a discontinuous single-column process that combines the aforementioned benefits: simple process configuration and hardware, high specific productivity, and low eluent consumption. The SSR concept has recently been commercialized by Novasep, France, (CycloJetTM) and licensed for example by CYBA Technologies Inc. (SteadyCycleTM) for pharmaceutical applications.

In the SSR process, overloaded injections are applied to the column. Two product fractions are obtained from the leading and tailing parts of the outlet profile, whereas the unresolved part is recycled. Several recycling schemes have been proposed. In closed-loop recycle, the recycled fraction from the column outlet is fed directly into the column inlet, followed or preceded by an injection of the fresh feed. In a mixed recycle mode, the recycled fraction is first mixed with the fresh feed prior to feeding into the column.

While some design procedures for SSR processes have been developed, a systematic methodology for arbitrary purity requirements is missing. In this work, the optimal design of SSR chromatography for the general case is investigated. The limiting case of infinite column efficiency is analyzed in the framework of equilibrium theory. Furthermore, a rapid optimization method, based on integration of the governing equations in the hodograph plane, is presented.

The influence of column efficiency is elucidated by means of numerical simulations. It is shown that the equilibrium theory based optimization can be used as an initial guess for optimization of SSR chromatography with reduced column efficiencies. Calculation results will be supported by experimental investigations of a model system.

Finally, a comparison of the performance of separations by SMB and SSR chromatography will be presented.