Enantioseparation of ibuprofen by supercritical fluid extraction

In this work influencing factors of enantioseparation of racemic ibuprofen via partial diastereomeric salt formation with R-(+)-phenylethylamine and subsequent supercritical fluid extraction (SFE) of the unreacted enantiomers were studied. It was demonstrated that conditions for diastereomeric salt formation and sample preparation (amount of resolution agent and achiral support, quality of solvent) have deep effects on SFE and on achievable resolution efficiency (F). Optimal value of the resolution agent/racemic ibuprofen molar ratio is 0.5. Addition of achiral support improves significantly the quality of the extraction bed and reduces the extraction time, but it has negligible effect on F. Solvent effects were studied using different organic solvents (acetone, dichloromethane, ethyl alcohol, ethyl acetate, methyl alcohol, methyl ethyl ketone and tetrachloromethane) and were compared to resolution in melt and suspension. It was demonstrated that solvents have important effect on F as well as on initial dissolution rates. Among SFE control parameters only pressure has significant effect on F precluding the possibility of pure density dependence.