Comparison and Rationalization of Droperidol Isostructural Solvate Stability: An Experimental and Computational Study

In order to find a tool for comparison of solvate stability and to rationalize their relative stability, droperidol nonstoichiometric isostructural solvates were characterized experimentally and computationally. For the experimental evaluation of stability, three comparison tools were considered: thermal stability characterized by the desolvation rate, desolvation activation energy, and solvent sorption-desorption isotherms. It was found that the desolvation process was limited by diffusion, and the same activation energy values were obtained for all of the characterized solvates, while the solvent content in the sorption isotherm was determined by the steric factors. Therefore, the only criterion characterizing the solvate stability in this particular system was the thermal stability. It was found that computationally obtained solvent droperidol and solvent solvent interaction energies could be used for the rationalization of the isostructural solvate stability in this system and that the solvent solvent interaction energy has a crucial role in determining the stability of solvates.