Wei Zhang, Jiacheng Li, Chao Yu, Zijie Zhang, Guoqiang Zhou, ZHANG Yue, Jiaqi Li, Yufei Zhang, Funeng Xu, Hualin Fu, Juchun Lin, Bo Jing, Gang Shu
• Focuses on oxibendazole (OXIB) solubility, guiding pharmaceutical formulation. • Measures OXIB solubility in 14 mono-solvents and 2 binary solvents (283.15–328.15 K). • Identifies optimal models (Apelblat, GSM) fo OXIB for solubility correlation. • Analyzes Hansen solubility parameters and activity coefficients to elucidate solvent-solute interactions. • Reveals OXIB dissolution is endothermic and entropy-driven. • Provides data for optimizing OXIB solvent selection and formulations. Oxibendazole (OXIB) is a benzimidazole anthelmintic for human and veterinary use, but its low water solubility limits bioavailability, and limited systematic solubility data hinder its purification and high-bioavailability formulation development. This study measured the mole fraction solubility of OXIB in 14 mono-solvents and 2 binary mixtures by the equilibrium method at 283.15–328.15 K (101.3 kPa). OXIB was characterized by DSC and PXRD to confirm no phase transition during dissolution. Solubility data were correlated with models including Apelblat, van’t Hoff, Jouyban, GSM, and Jouyban-Acree model, with accuracy assessed by RMSD. Simultaneously, Hansen solubility parameter analysis, ideal solubility analysis, and solubility thermodynamic parameter analysis were conducted. Results showed OXIB solubility rose markedly with temperature in all solvents. Among mono-solvents, solubility was highest in DMA followed by DMF, affected by hydrogen bonding, steric hindrance, and intermolecular interactions. In mixtures, solubility increased monotonically with DMF/DMA content, and was higher in DMA/isopropanol than DMF/isopropanol at the same ratio. The Apelblat model performed best for mono-solvents, and GSM for mixtures (all ORMSD < 0.02%). Thermodynamic analysis revealed non-spontaneous (ΔG ⁰ sol > 0), endothermic (ΔH ⁰ sol > 0), entropy-driven (ΔS ⁰ sol > 0) dissolution, with enthalpy contributing >70.6% to Gibbs free energy change. This work provides key data for OXIB purification, crystallization optimization, and formulation development. This study presents the first comprehensive dataset for OXIB solubility in 14 mono-solvents and 2 binary mixtures within 283.15–328.15 K, together with HSP analysis and thermodynamic characterization. These results are of great importance for the solvent screening and crystallization design optimization of benzimidazole compounds.