Molecular separation with an organic solvent nanofiltration cascade – augmenting membrane selectivity with process engineering

While it is known that organic solvent nanofiltration (OSN) can be used to recycle solvents, most commercial membranes do not retain active pharmaceutical ingredients (API) sufficiently to enable solvent recovery in a single stage membrane process. A multistage membrane cascade might be used to augment the overall rejection. However there have been no examples shown, to date, of this approach to concurrent API enrichment and organic solvent recovery. In this work, the development of a membrane cascade design is described. The use of this automated multistage cascade, for the concentration of a dilute API product solution and concurrent solvent recovery downstream of a chromatographic process, was demonstrated. The 3-stage cascade was able to achieve an effective rejection of 80% compared to a single pass rejection of 55%. Control of the cascade was simple and its operation was stable. Furthermore, the low permeation selectivity of one solvent over another across the membrane meant that solvent composition did not change significantly in the cascade. As a result no additional heat needs to be applied to keep the solutes in solution if such a system were to be used for solvent recovery. This is especially advantageous for processing of thermally sensitive API. ▸ Developed an automated cascade utilising organic solvent nanofiltration membranes. ▸ Concurrently concentrated an API and recovered organic solvents with the cascade. ▸ Validated the process model, which is intuitive and simple to use. ▸ Process saves energy compared to flash-condensation. ▸ Process becomes economical with moderate improvements to membrane performance.