(293b) Membrane Cascade with Solvent Recovery – Process Innovation for the Purification of Molecules

Authors: 
Chen, W., Imperial College London
Kim, J. F., Hanyang University
Szekely, G., The University of Manchester
Peeva, L., Imperial College London
Sereewatthanawut, I., Membrane Extraction Technology Ltd.
Sharifzadeh, M., Imperial College London
Shah, N., Imperial College London
Livingston, A., Imperial College London

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.