Solubility Data and Computational Modeling of Baricitinib in Various (DMSO + Water) Mixtures

• Main Authors: Saad M. Alshahrani, Faiyaz Shakeel
• Format: Article
• Language: English
• Published: MDPI AG 2020-05-01
• Series: Molecules
• Subjects: activity coefficient; baricitinib; co-solvency models; solubility; thermodynamics
• Online Access: https://www.mdpi.com/1420-3049/25/9/2124

The solubility and thermodynamic analysis of baricitinib (BNB) in various dimethyl sulfoxide (DMSO) + water mixtures were performed. The “mole fraction solubilities (<i>x</i>_e)” of BNB in DMSO and water mixtures were determined at “<i>T</i> = 298.2–323.2 K” and “<i>p</i> = 0.1 MPa” using an isothermal saturation technique. “Hansen solubility parameters (HSPs)” of BNB, pure DMSO, pure water and “DMSO + water” mixtures free of BNB were also estimated. The <i>x</i>_e data of BNB was regressed well by five different thermodynamics-based co-solvency models, which included “Apelblat, Van’t Hoff, Yalkowsky-Roseman, Jouyban-Acree and Jouyban-Acree-Van’t Hoff models” with overall deviations of <5.0%. The highest and lowest <i>x</i>_e value of BNB was computed in pure DMSO (1.69 × 10⁻¹ at <i>T</i> = 323.2 K) and pure water (2.23 × 10⁻⁵ at <i>T</i> = 298.2 K), respectively. The HSP of BNB was found to be closer to that of pure DMSO. Based on activity coefficient data, maximum solute–solvent molecular interactions were observed in BNB-DMSO compared to BNB-water. The results of “apparent thermodynamic analysis” indicated endothermic and entropy-drive dissolution of BNB in all “DMSO + water” combinations including mono-solvents (water and DMSO). “Enthalpy-entropy compensation analysis” showed enthalpy-driven to be the main mechanism of solvation of BNB.