Analysis of agomelatine (Form Ⅱ) dissolution behavior in different mono-solvents: Solubility, solvation thermodynamics as well as inter-molecular interactions

Form II of Agomelatine (AG) is a stable crystal which can be applied to industrial production, and it is mainly used for the treatment of depression. In this paper, the solubility of AG in ten single solvents was determined by the laser dynamic method, and the solubility data were fitted and analyzed using the activity coefficient model and empirical equations (NRTL,λh, Apelblat and Van't Hoff). Besides, the thermodynamic properties of the mixing and dissolution processes were estimated. The compatibility between Agomelatine and selected solvents was analyzed based on HSP, the Hansen Solubility Parameter. On the basis of the Hirshfeld partition (IGMH), the study applied the independent gradient model and the molecular surface to qualitatively elaborate the electrostatic characteristics of the acidity and basicity of Agomelatine. The results show that compared with the other ester solvents, the = O, and > NH groups in the Agomelatine molecule have priority over forming hydrogen bonds with the alcohol solvents. The molecular dynamics simulation of Agomelatine in different solvent systems was conducted by using the Materials studio software, the interaction force between the solute–solvent molecules in the solution was calculated, and the reasons for the solubility difference of Agomelatine in various solvents were analyzed.