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

## TL;DR

This study examines how the length of carbon chains in coformers affects the properties of haloperidol drug forms to improve solubility and stability.

## Contribution

The study introduces a rational strategy for coformer selection in haloperidol salts to enhance drug performance.

## Key findings

- X-ray diffraction and DFT calculations reveal how coformer carbon-chain length affects crystal structures.
- Longer carbon chains improve solubility and stability of haloperidol multicomponent materials.
- Mechanochemical synthesis and thermal analysis confirm the impact of coformer structure on drug properties.

## Abstract

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.

This study explores the impact of carbon-chain length in
dicarboxylic acid coformers on the structure and properties of haloperidol
salts and ionic cocrystals. Evidence from X-ray diffraction, DFT calculations,
and thermal analysis supports a rational coformer selection strategy
to enhance solubility and stability in haloperidol multicomponent
materials.