IBUPROFEN RACEMATE AND ENANTIOMERS - PHASE-DIAGRAM, SOLUBILITY AND THERMODYNAMIC STUDIES

A binary phase diagram constructed from DSC curves of ibuprofen (IB) using R-IB, S-IB and ibuprofen USP (rac-IB) was typical of a eutectic system with addition compound formation. The USP material is therefore a racemic compound which melts at 71-degrees-C compared with 46-degrees-C for the enantiomers and 37-degrees-C for the eutectic compositions of 0.18 and 0.82 mole fractions of S-IB. The phase diagram was verified by calculation of the liquidus curve in the dystectic region using a rearrangement of the Prigogine-Defay equation. Powder X-ray diffraction analysis confirmed that rac-IB was a racemic compound, capable of existing as a separate phase independent of its constituent enantiomers, and not a racemic mixture. Solubilities in aqueous HCl-KCl solution, pH 1.5, were in the order eutectic-IB > R-IB or S-IB > rac-IB with eutectic-IB having twice the solubility of rac-IB. The solubility-temperature data were non-linear and could not be fitted to either van't Hoff or Hildebrand plots. A multiple regression analysis was used. The enthalpy, entropy and free energy of formation of rac-IB from R-IB and S-IB were calculated from DSC observations.