Membrane Cascade with Solvent Recovery – Process Innovation for the Purification of Molecules

For the purification of a target compound from impurities, an ideal membrane should completely retain the former while allowing the latter to permeate through or vice versa. In real life, the purification process is often a trade-off between the yield and purity of the target compound due to the non-ideality of the membranes used. For example, the separation of of polyethylene glycol (PEG) 400 from PEG 2000 by constant volume diafiltration (CVD) in a single-stage membrane system resulted in a 41% yield loss of PEG 2000 in order to achieve 98% purity, although the rejection of PEG 2000 was substantially higher than that of PEG 400 (96% and 51% respectively)¹. By installing a second-stage membrane to recover the PEG 2000 that permeated through the first-stage membrane, the yield loss was greatly reduced to only 6% with the same final purity. Similarly, the modelling of the Membrane Enhanced Peptide Synthesis (MEPS) in a two-stage membrane cascade shows that a significantly higher yield of final peptide (98 % versus 71 % in a single-stage process) can be achieved with a similar purity (93%). These examples suggest that the use of membrane cascades can overcome the problem of non-absolute rejection of the desired product and maintain high yields for a similar purity of the target compound at the expense of a larger consumption of fresh solvent than a single-stage process. To reduce this solvent consumption and the associated material cost and environmental impact, solvent recovery can be performed downstream. In a case study of the separation of an active pharmaceutical ingredient (API) (roxithromycin macrolide antibiotic (Roxi)) from genotoxic impurities (GTIs) (4-dimethylaminopyridine (DMAP) and ethyl tosylate (EtTS)), adsorptive solvent recovery by activated carbon exhibited lower energy consumption and a smaller carbon footprint than distillation (96% and 70% lower respectively)². Alternatively, solvent recovery through a tight membrane is also technically feasible as demonstrated in two case studies where the requirement of fresh solvent (tetrahydrofuran (THF)) was reduced by 90% in the first case³ and where membrane-based solvent recovery outperformed adsorptive- and distillation-based solvent recovery in terms of operability and carbon footprint in the second case⁴. In short, diafiltration in membrane cascade coupled with downstream solvent recovery is a promising process for the purification of compounds in the chemical industry. 

Reference:

1.  Kim, J. F., da Silva, A. M. F., Valtcheva, I. B., & Livingston, A. G. (2013). When the membrane is not enough: A simplified membrane cascade using Organic Solvent Nanofiltration (OSN). Separation and Purification Technology, 116, 277-286.

2.  Kim, J. F., Székely, G., Valtcheva, I. B., & Livingston, A. G. (2014). Increasing the sustainability of membrane processes through cascade approach and solvent recovery—pharmaceutical purification case study. Green Chemistry, 16(1), 133-145.

3.   Sereewatthanawut, I., Lim, F. W., Bhole, Y. S., Ormerod, D., Horvath, A., Boam, A. T., & Livingston, A. G. (2010). Demonstration of molecular purification in polar aprotic solvents by organic solvent nanofiltration. Organic Process Research & Development, 14(3), 600-611.

4.     Kim, J. F., Szekely, G., Schaepertoens, M., Valtcheva, I. B., Jimenez-Solomon, M. F., & Livingston, A. G. (2014). In Situ Solvent Recovery by Organic Solvent Nanofiltration. ACS Sustainable Chemistry & Engineering,2(10), 2371-2379.