Uncovering the Solution Thermodynamic Properties of Esmolol Hydrochloride: Experiments and Molecular Simulations

Esmolol hydrochloride (EH) is a highly selective β-adrenergic antagonist commonly employed in the management of atrial fibrillation and nodal tachycardia. In this work, the solubility of EH Form A in 12 organic solvents were measured and correlated with five thermodynamic models, and the fitting results were all satisfactory. Additionally, molecular simulations were employed to explore the mechanisms underlying the varying solubilities of EH, and Hirshfeld surface analysis (HS) was used to determine the internal interactions between the molecules. Besides, molecular electrostatic potential surface, radial distribution function, and solvation free energy were also performed. The findings demonstrate that the solubility is strongly influenced by the solute–solvent interaction strength. Finally, the dissolution thermodynamic properties of EH were calculated, which indicates that the dissolution process is endothermic, entropy-driven, and spontaneous.