Impact of the Coformer Carbon-Chain Length on the Properties of Haloperidol Pharmaceutical Salts.

Haloperidol (HAL) is a conventional antipsychotic drug with poor aqueous solubility, which is associated with a major risk of side effects. In this context, crystal engineering has provided an efficient approach for tuning the physicochemical properties of active pharmaceutical ingredients (APIs). However, there is a huge lack of knowledge about how coformer molecules impact the pharmaceutical properties of the multicomponent materials, with special attention to solubility and stability. To this purpose, five novel salts and three ionic cocrystals were synthesized using HAL and a series of closely related dicarboxylic acid counterions. Mechanochemical strategies were applied for synthesis, while thermal, spectroscopic, and X-ray diffraction techniques were used for a complete characterization of the materials. By understanding the relationships between the crystal structures and the final properties, this research seeks to inform the rational design of HAL multicomponent drugs, providing a framework for improving the performance of not only HAL but also other APIs with similar challenges.