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

Abstract

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.

Solubility and Thermodynamic Properties of Febuxostat in Various (PEG 400 + Water) Mixtures

“…To look into the potential conversion of FXT into polymorphs or solvates/hydrates, the solid phase characterization of FXT before solubility measurement (pure FXT) and after solubility measurement (equilibrated FXT recovered from H 2 O) was conducted. Our most recent work [ 32 ] reports the results of this characterization on pure and equilibrated FXT utilizing Fourier transforms infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses. In our most recent publication [ 32 ], it was discovered that the FTIR and XRD spectra of pure and equilibrated FXT were identical and shared similar peak characteristics.…”

“…Our most recent work [ 32 ] reports the results of this characterization on pure and equilibrated FXT utilizing Fourier transforms infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses. In our most recent publication [ 32 ], it was discovered that the FTIR and XRD spectra of pure and equilibrated FXT were identical and shared similar peak characteristics. Additionally, no other FTIR or XRD peaks were seen in the equilibrated FXT sample.…”

“…Three replicates of experiments were run. The resulting samples were saturated in the “WiseBath ® WSB Shaking Water Bath (Model WSB-18/30/-45, Daihan Scientific Co. Ltd., Seoul, Korea)” for 72 h in order to reach equilibrium [ 32 ]. After reaching equilibrium, the saturated samples were removed from the shaker and centrifuged at 5000rpm for 30 min.…”

“…After reaching equilibrium, the saturated samples were removed from the shaker and centrifuged at 5000rpm for 30 min. A previously described HPLC method at 354 nm was used to measure the FXT concentration after the supernatants were extracted and diluted (as necessary) [ 32 ]. FXT mole fraction solubilities ( x e ) were computed using Equations (1) and (2): where, m 1 = FXT mass, m 2 = PEG 400 mass, m 3 = H 2 O mass, M 1 = FXT molar mass, M 2 = PEG 400 molar mass, and M 3 = H 2 O molar mass.…”

“…The literature contains a good report on FXT solubility in four different neat solvents, including methanol, ethanol, acetone, and ethyl acetate, at several temperatures under atmospheric pressure [ 1 ]. The solubility of FXT in eleven different pure solvents, including H 2 O, methanol, ethanol, isopropanol, 1-butanol, 2-butanol, ethylene glycol, propylene glycol, PEG 400, Carbitol, and dimethyl sulfoxide, was recently reported by us [ 32 ]. FXT solubility in supercritical carbon dioxide at 308–338 K and 100–270 bar has also been documented recently [ 33 ].…”