Solubility and Solution Thermodynamics of Baricitinib in Six Different Pharmaceutically Used Solvents at Different Temperatures

The preset study was undertaken to determine solubility and solution thermodynamics of a novel anticancer drug baricitinib in some pharmaceutically used mono/pure solvents including "water, ethanol, polyethylene glycol-400 (PEG-400), ethyl acetate (EA), dichloromethane (DCM) and dimethyl sulfoxide (DMSO)" at "T = 298.2 K to 323.2 K" and "p = 0.1 MPa". The solubility of baricitinib after equilibrium (saturation state) was analyzed spectrophotometrically by applying an isothermal technique. Characterization of solid phases of initial and equilibrated baricitinib was confirmed with the help of differential scanning calorimetry (DSC). Measured solubilities of baricitinib were regressed using "van't Hoff and Apelblat models". DSC spectra of baricitinib showed no change in physical state of baricitinib after equilibrium. Solubilities of baricitinib (as mole fraction) were estimated highest in DMSO (1.65 × 10^-1) followed by PEG-400 (1.42 × 10^-1), DCM (1.29 × 10^-3), ethanol (7.41 × 10^-4), EA (4.74 × 10^-4) and water (1.76 × 10^-4) at "T = 323.2 K" and same tendencies were also noted at other temperatures studied. With the help of theoretical solubilities of baricitinib, activity coefficients were estimated. The estimated data of activity coefficients indicated higher molecular interactions in baricitinib-DMSO and baricitinib-PEG-400 as compared with baricitinib-water, baricitinib-EA, baricitinib-DCM and baricitinib-ethanol. Thermodynamic treatment of solubility values of baricitinib showed "endothermic and entropy-driven dissolution" of baricitinib in all pharmaceutically used solvents evaluated.