40 years later: completion of the structural characterization of the anxiolytic drug buspirone HCl and solid-form landscape expansion.

Buspirone (Bus) is an anxiolytic drug and was commercialized forty years ago as an HCl salt. The HCl salt of Bus is also polymorphic, and here, using electron diffraction, we reveal the structure of Bus·HCl Form 2 for the first time. We also prepared the first multicomponent solids of Bus, and describe 15 solids, including cocrystals, an ionic cocrystal, and salts. Significant differences in the solid-state conformation of Bus are described, as well as impacts to the thermal properties upon incorporation into multicomponent solids. Bus, like many drug molecules, does not include a classic ionizable group, which could hamper solid-state development. Bus does include a piperazine ring, one of the five most frequently used nitrogen-based heterocycles in US FDA approved drugs, and is a key site for forming intermolecular hydrogen bonds in each solid. The strategies here could be applied to modify properties in other piperazine-containing drugs.