Nanofiltration-Enabled In†Situ Solvent and Reagent Recycle for Sustainable Continuous-Flow Synthesis.

Solvent usage in the pharmaceutical sector accounts for as much as 90 % of the overall mass during manufacturing processes. Consequently, solvent consumption poses significant costs and environmental burdens. Continuous processing, in particular continuous-flow reactors, have great potential for the sustainable production of pharmaceuticals but subsequent downstream processing remains challenging. Separation processes for concentrating and purifying chemicals can account for as much as 80 % of the total manufacturing costs. In this work, a nanofiltration unit was coupled to a continuous-flow rector for in situ solvent and reagent recycling. The nanofiltration unit is straightforward to implement and simple to control during continuous operation. The hybrid process operated continuously over six weeks, recycling about 90 % of the solvent and reagent. Consequently, the E-factor and the carbon footprint were reduced by 91 % and 19 %, respectively. Moreover, the nanofiltration unit led to a solution of the product eleven times more concentrated than the reaction mixture and increased the purity from 52.4 % to 91.5 %. The boundaries for process conditions were investigated to facilitate implementation of the methodology by the pharmaceutical sector.

Exploring and Exploiting the Effect of Solvent Treatment in Membrane Separations.

It is well-known that solvent treatment and preconditioning play an important role in rejection and flux performance of membranes due to solvent-induced swelling and solvent adsorption. Investigations into the effect of solvent treatment are scarce and application specific, and were limited to a few solvents only. This study reveals the trend in solvent treatment based on solvent polarity in a systematic investigation with the aim to harness such effect for intensification of membrane processes. Nine solvents with polarity indices ranging from 0.1 to 5.8 (hexane to acetonitrile) were used as treatment and process solvents on commercial Borsig GMT-oNF-2, Evonik Duramem 300, and emerging tailor-made polybenzimidazole membranes. TGA-GCMS, HS-GC-FID, and NMR techniques were employed to better understand the effect of solvent treatment on the polymer matrix of membranes. In this work, apart from the solvent treatment's direct effect on the membrane performance, a subsequent indirect effect on the ultimate separation process was observed. Consequently, a pharmaceutical case study employing chlorhexidine disinfectant and antiseptic was used to demonstrate the effect of solvent treatment on the nanofiltration-based purification. It is shown that treatment of polybenzimidazole membranes with acetone resulted in a 25% increase in product recovery at 99% impurity removal. The cost of the process intensification is negligible in terms of solvent consumption, mass intensity, and processing time.