Continuous solute fractionation with membrane cascades – A high productivity alternative to diafiltration

Abstract Two new solute fractionating membrane cascade configurations have been proposed, with the aim of introducing a flexible solute fractionation system that can be modified rapidly. Solute fractionation, using a cascade where the more permeable solute is stripped, has been simulated. It was shown that the separation performance was driven by the relative permeability of solutes through the membrane. This cascade can reduce solvent usage significantly and increase separation yield with minimal stages added. Furthermore, the cascade is more productive and effective in solute fractionation than constant volume diafiltration. The development of a fractionation strategy for the separation of a developmental active pharmaceutical ingredient (API) from an excess reagent is described and was demonstrated using a 3-stage permeable stripping cascade. A binary feed solution, containing the API and the excess reagent, was stripped of the reagent to produce a product stream enriched in the API. This product stream could be further polished using a single crystallisation step, which was otherwise impossible with the original feed solution. The proposed process model was shown to be in general agreement with experimental data.