Solubility and Thermodynamic Data of Febuxostat in Various Mono Solvents at Different Temperatures

This study examines the solubility and thermodynamics of febuxostat (FBX) in a variety of mono solvents, including “water, methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO)” at 298.2–318.2 K and 101.1 kPa. The solubility of FBX was determined using a shake flask method and correlated with “van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models”. The overall error values for van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models was recorded to be 1.60, 2.86, and 1.14%, respectively. The maximum mole fraction solubility of FBX was 3.06 × 10(−2) in PEG-400 at 318.2 K, however the least one was 1.97 × 10(−7) in water at 298.2 K. The FBX solubility increased with temperature and the order followed in different mono solvents was PEG-400 (3.06 × 10(−2)) > THP (1.70 × 10(−2)) > 2-BuOH (1.38 × 10(−2)) > 1-BuOH (1.37 × 10(−2)) > IPA (1.10 × 10(−2)) > EtOH (8.37 × 10(−3)) > EA (8.31 × 10(−3)) > DMSO (7.35 × 10(−3)) > MeOH (3.26 × 10(−3)) > PG (1.88 × 10(−3)) > EG (1.31 × 10(−3)) > water (1.14 × 10(−6)) at 318.2 K. Compared to the other combinations of FBX and mono solvents, FBX-PEG-400 had the strongest solute-solvent interactions. The apparent thermodynamic analysis revealed that FBX dissolution was “endothermic and entropy-driven” in all mono solvents investigated. Based on these findings, PEG-400 appears to be the optimal co-solvent for FBX solubility.