Effect of Solvent Composition and Temperature on the Solubility of Ibuprofen in Aqueous Ethanol

The solubilities of ibuprofen [(R,S)-2-(4-(2-methylpropyl)phenyl)propanoic acid] in absolute ethanol and in water–ethanol mixtures were measured at temperatures from 10 °C to 40 °C, the expected range relevant to its industrial crystallization. The solubility studies were carried out by dissolution of ibuprofen crystals in stirred Schott bottles kept in a constant temperature bath. The ibuprofen concentration in the clear supernatant at equilibrium was determined by vacuum drying. An allowance was made for the small amount of sublimation from dried ibuprofen. In absolute ethanol, the experimental results showed that the solubility increased as a square law with temperature, from 0.59 g of ibuprofen/g ethanol at 10.0 °C to 2.15 g/g at 40.0 °C. The results are considered to be accurate to within ±1% (as 95% confidence). In water–ethanol mixtures, the solubility of ibuprofen (expressed as w/w ibuprofen/solvent) generally decreased with increasing water addition. At 40 °C and possibly at 25 °C, the solubility initially increased slightly to a maximum level as a small amount of water was added before then decreasing. At 40 °C, phase separation into two immiscible liquid layers was observed for solvent concentrations from 34 to 64% ethanol on an ibuprofen-free basis.