Nitazoxanide in aqueous co-solvent solutions of isopropanol/DMF/NMP: Solubility, solvation thermodynamics and intermolecular interactions

Abstract

At the microscopic level, quantitative surface analysis was utilized to highlight the electrostatic features of acidity and basicity, respectively. The groups of –NO2 and > NH are the principal sites of electrophilic and nucleophilic attack, respectively, on the nitazoxanide (NTZ) molecule. The weak interaction regions between NTZ and solvent were visually examined through the IGMH method. The solubility of NTZ in three co-solvent blends, namely isopropanol + water, DMF + water, and NMP + water, was determined over a temperature range of 278.15 to 323.15 K. The isothermal saturation method was used to obtain the results, which were carried out under a pressure of 101.2 kPa. No evidence of crystal transition or solvate production was observed in the experiments conducted. Under the same investigational conditions, such as the same temperature and composition of isopropanol (DMF or NMP), the NTZ solubility in mole fraction was significantly greater in aprotic DMF/NMP + water blends than in protic isopropanol + water blends. Five models were used to relate solubility data: the Jouyban–Acree model, the extended Hildebrand solubility model, the modified Jouyban–Acree-van't Hoff model, the NRTL model and the UNIQUAC model. Under the conditions of 298.15 K, an investigation into the preferential solvation of NTZ was carried out using a technique based on inverse Kirkwood–Buff integrals. With isopropanol/DMF/NMP-medium and -rich composition areas, the preferential solvation parameters of NTZ showed positive values, indicating that the co-solvents were preferentially solvating the drug.