Novel perfluorinated nanofiltration membranes for isolation of pharmaceutical compounds

Polymeric membranes for separation of pharmaceutical intermediates/products by organic solvent nanofiltration (OSN) have to be highly resistant to many organic solvents including high-boiling polar aprotic ones, e.g., N-methyl-2-pyrollidone (NMP), dimethylsulfoxide (DMSO), dimethylformamide (DMF). Unless cross-linked, few polymers resist swelling or dissolution in such solvents; however particular perfluoropolymers are resistant to almost all solvents except perfluorosolvents. One such polymer, designated AHP1, a glassy amorphous hydrophobic perfluorinated polymer, has been studied here. Additional perfluoropolymers studied here are hydrophilically modified (HMP2 and HMP3) versions to enhance the flux of polar aprotic solvents. OSN performances of three types of membranes including the hydrophilically modified ones were studied via solvent flux and solute rejection at pressures up to 5000 kPa. The solutes were four active pharmaceutical ingredients (APIs) or pharmaceutical intermediates having molecular weights (MWs) between 432 and 809 Da and three dyes, Oil Blue N (378 Da), Sudan Black B (456 Da), Brilliant Blue R (826 Da). Solvents used were: ethyl acetate, toluene, n-heptane, iso-octane, DMSO, tetrahydrofuran (THF), DMF, acetone, NMP, methanol. Test cells included stirred cells and tangential flow cells. Pure solvent fluxes through three membrane types were characterized using a particular parameter employing various solvent properties. All three membranes achieved high solute rejections around 91–98% at ambient temperatures. HMP2 membrane achieved 95% solute rejection for an API (809 Da) in DMSO at a high temperature, 75 °C. A two-stage simulated nanofiltration process achieved 99%+ rejection of a pharmaceutical intermediate (MW, 432 Da) in 75v% NMP-25v% ethyl acetate solution.