Membrane-assisted chiral resolution of pharmaceuticals: Ibuprofen separation by ultrafiltration using bovine serum albumin as chiral selector

The chiral separation of ibuprofen has been performed by ultrafiltration in solutions containing the protein bovine serum albumin (BSA) as a chiral selector. The effectiveness of optical resolution was characterized in terms of enantionteric enrichment and solute recovery in the permeate. Working conditions, including parameters of feed solution and hydrodynamic conditions, which can influence thermodynamic equilibrium and nonselective solute binding, have been investigated with regard to the separation effectiveness. Enantioselectivity is strongly pH-dependent and reaches a maximal value at pH 9.0-9.2. It was established that nonspecific interactions also played a significant role in total ibuprofen binding, decreasing both enantioselectivity and solute recovery in permeates. Nonspecific interactions are suppressed in the presence of organic solvents (acetonitrile, methanol) in the feed solution thereby increasing the solute recovery in the permeate. Increase in BSA content in the feed solution results in an increase of both enantioselectivity and solute binding. In ultrafiltration-based chiral separation, concentration polarization and gel formation worsen enantioselectivity and increase solute binding. A consequent enrichment of enantiomers was illustrated in a multi-stage chiral resolution. After six stages of separation, the permeate contains more than 95% of (S)-ibuprofen. Regeneration of both BSA and bound enantiomer may be fulfilled in the same ultrafiltration system by ultrafiltration of alkaline solutions.