Solubility Profile and Intermolecular Force Analysis of Nimesulide (Form I) in Mono- and Mixed Solvents at Several Temperatures

Abstract

The solubility data of nimesulide (form I) in different mono- and mixed solvents over the temperature range from 273.15 to 318.15 K are determined. In this work, it is further studied to improve the solubility data of nimesulide (form I) and analyze the intermolecular force. The solubility profiles in mono- and mixed solvents are correlated by some thermodynamic models. The results of statistical analysis show that all selected models could provide a good correlation of the dissolution profile for nimesulide in selected solvents at all investigated temperatures. At 318.15 K, the largest solubility in mole fraction is obtained in acetone (7.812 × 10–2), followed by 2-butanone (6.334 × 10–2), cyclohexanone (4.977 × 10–2), ethyl acetate (3.803 × 10–2), tetrahydrofuran (3.651 × 10–2), acetonitrile (2.975 × 10–2), ethanol (2.169 × 10–3), toluene (1.788 × 10–3), isobutanol (1.348 × 10–3), isopropanol (1.201 × 10–3), and propylene glycol (PG, 6.764 × 10–4). However, in mixtures of (ethyl acetate + isopropanol), the solubility data increase with the increase of the mass fraction of ethyl acetate at a given temperature. The effect of solute–solvent interactions on the solid–liquid phase equilibrium of the solute is discussed with the solvent properties. The calculation of preferential solvation parameters shows that solute molecules are preferentially solvated by isopropanol in isopropanol-rich regions and as the mass fraction of ethyl acetate increases, nimesulide is preferentially solvated by ethyl acetate. Studying the dissolution process of nimesulide is of great practical significance for its purification.