Experimental and Computational Investigation of Benperidol and Droperidol Solid Solutions in Different Crystal Structures

Abstract

We present an experimental and computational study of solid solution formation between structurally highly similar active pharmaceutical ingredients droperidol and benperidol in nonsolvates, dihydrates, and several solvates formed by these compounds. We demonstrate that the formation of solid solutions strongly depends on the crystal structure of the phase. In some of the structures, almost complete replacement of benperidol with droperidol can be achieved, whereas in other structures, the replacement is possible only up to a limited molar ratio. However, only limited replacement of droperidol with benperidol can be achieved and only in some of the structures. The solid solution formation is primarily determined by the change in intermolecular interaction energy resulting from the molecule replacement. Only structures where molecule replacement allows the formation of efficient intermolecular interactions can be obtained experimentally. The results indicate that the energy requirements of intermolecular interaction changes to obtain solid solutions in the nonsolvated phase are less strict than those for solvates.