Research on solubility modelling of actarit in different solvents: Solvent effect, Hansen solubility parameter, molecular interactions and solution thermodynamics

Abstract

The solubility as an important property should be known in terms of design and development of dosage form, screening of crystal forms along with purification and production for pharmaceuticals. The phase equilibrium solubility of actarit in different solvents (methanol, ethanol, acetone, water, 1-propanol, 2-propanol, 2-butanone, 1-butanol, acetonitrile, cyclohexane, ethyl acetate and toluene) within the scope of 278.15 K to 318.15 K at 5 K intervals was measured by making use of isothermal saturation method. The solubility of actarit presented a positive relationship to temperature, and increased with temperature rise. The outcomes demonstrated that the tendency of solubility was methanol > ethanol > 1-propanol > 2-butanone > 1-butanol > acetone > 2-propanol > acetonitrile > ethyl acetate > water > toluene > cyclohexane. The topological index (H) was established to investigate the influence of solvents’ physical properties on solubility of actarit. The Hansen solubility parameter (HSP) was applied to evaluate the dissolving capacity of solvents to actarit. Solvent effect was discussed, and solute–solvent interactions had more contribution to solubility of actarit. In addition, the activity coefficients which reflected the interactions were calculated and used to evaluate the solubility more deeply by molecular interactions at molecular level. Moreover, four thermodynamics models (Apelblat model, λh model, Wilson model and NRTL model) were used to correlate the experimental solubility data of actarit in different solvents. The relative average deviation (RAD) and root-mean-square deviation (RMSD) values were no>1.98% and 4.18 × 10-4, respectively. Then Akaike Information Criterion (AIC) was used to assess suitability of these four models, and Apelblat model was the best model among four models because of the lowest AIC value occurred in Apelblat model. Finally, the thermodynamic properties were computed van't Hoff analysis, and the values were all positive which demonstrated that this process was an entropy driven and endothermic process.