Effect of membrane fouling on chiral separation

Abstract Chiral purity is becoming increasingly critical particularly for the pharmaceutical industry. Compared to the conventional techniques, membrane-based separation is promising as an easily scalable, efficient, continuous operation. Past studies have proven the efficacy of membranes for such separations, but the knowledge available on such processes remain limited. Since membrane fouling is well acknowledged to be one of the key impediments to more widespread implementation of membrane-filtration processes, this study was targeted at addressing the question of whether a relationship exists between the extents of membrane fouling and chiral purification. Another goal was to provide a more comprehensive understanding of the effect of various operating parameters (namely, chiral concentration, ratio of chiral selector to chiral concentrations, pH, feed medium and cross-flow velocity (CFV)) on the extent of chiral separation. The membrane was a non-chiral-selective polyethersulfone ultrafiltration membrane, the chiral selector was bovine serum albumin (BSA), while the chiral species was D,L-phenylalanine (Phe). Higher Phe concentrations decreased the separation factor and increased flux decline, while the highest separation factor was at an intermediate ratio of BSA to Phe concentration and an intermediate flux decline. Also, an intermediate pH of 9 gave the highest separation factor but extensive flux decline, and phosphate buffered saline (PBS) gave better separation and lesser flux decline than water as the feed medium. Regarding cross-flow velocity, the separation factor increased with CFV and decreased with flux decline. With respect to the relationship between the extents of chiral purification and flux decline, a poor correlation between the two existed, which suggests that improving membrane-based chiral separation requires means to improve the binding between the chiral selector and chiral species, rather than the conventional strategies to mitigate membrane fouling.