On the Formation of Droperidol Solvates: Characterization of Structure and Properties

A solvate screening and characterization
of the obtained solvates
was performed to rationalize and understand the solvate formation
of active pharamaceutical ingredient droperidol. The solvate screening
revealed that droperidol can form 11 different solvates. The analysis
of the crystal structures and molecular properties revealed that droperidol
solvate formation is mainly driven by the inability of droperidol
molecules to pack efficiently. The obtained droperidol solvates were
characterized by X-ray diffraction and thermal analysis. It was found
that droperidol forms seven nonstoichiometric isostructural solvates,
and the crystal structures were determined for five of these solvates.
To better understand the structure of these five solvates, their solvent
sorption–desorption isotherms were recorded, and lattice parameter
dependence on the solvent content was determined. This revealed a
different behavior of the nonstoichiometic hydrate, which was explained
by the simultaneous insertion of two hydrogen-bonded water molecules.
Isostructural solvates were formed with sufficiently small solvent
molecules providing effective intermolecular interactions, and solvate
formation was rationalized based on already presented solvent classification.
The lack of solvent specificity in isostructural solvates was explained
by the very effective interactions between droperidol molecules. Desolvation
of stoichiometric droperidol solvates produced one of the four droperidol
polymorphs, whereas that of nonstoichiometic solvates produced an
isostructural desolvate.