Nanofiltration studies of larger organic microsolutes in methanol solutions

Multistep organic solvent-based pharmaceutical syntheses of larger organic microsolutes having molecular weights (MW) in the range of 300–1000 generally require athermal separation processes because the active molecules and the intermediates are thermally labile. To that end, nanofiltration (NF) of methanol solutions of three selected solutes, safranin O (MW 351), brilliant blue R (MW 826) and vitamin B12 (MW 1355) has been studied in a batch stirred cell for a dilute solution of each individual solute at 3034 kPa (440 psig). The solvent-resistant membranes investigated and their manufacturer-specified molecular weight cut-offs (MWCO) are MPF-44 (250), MPF-50 (700) and MPF-60 (400). During an initial transient period, the solvent flux decreased with time and the solute rejection increased with time for every membrane reaching a steady state after about 12 h. This behavior resulting from membrane compaction and pore size reduction was partially reversible. Additional studies using higher feed solute concentrations (1 and 3 wt.%) show considerable reduction in solvent flux and increase in solute rejection; the effect appears to be far more than that due to an increase in osmotic pressure and possible reasons for such a behavior have been suggested. The observed solute rejection values are generally significantly lower than the manufacturer-specified MWCO values. Additional studies varying the feed solution pressure through the membrane MPF-60 indicate that the variation of the percent rejection of solutes safranin O and brilliant blue R with the solvent flux tends to follow the relation suggested by the Finely Porous Model.