Polymorphic Cocrystals of Nutraceutical Compound p‑Coumaric Acid with Nicotinamide: Characterization, Relative Solid-State Stability, and Conversion to Alternate Stoichiometries

Nutraceutical compound p-coumaric acid, a phytochemical that possesses antioxidant and anti-inflammatory properties, was cocrystallized with nicotinamide, a member of the vitamin B complex, resulting in the discovery of three polymorphic 1:1 cocrystals. Slurries of two forms of the 1:1 cocrystal in water induced conversion to a 2:1 (p-coumaric acid-nicotinamide) cocrystal. In situ monitoring of this conversion at limited conditions by dispersive Raman spectroscopy illustrates rapid incomplete transformation. Additionally, a variety of conditions were evaluated to reach complete conversion. All four cocrystals were characterized by X-ray powder diffraction, thermal analyses, and spectroscopic techniques. In addition, single crystal structures for two of the 1:1 polymorphic cocrystals are presented. Further, competitive slurries, isothermal solution calorimetry, and differential scanning calorimetry analyses at a variety of heating rates were employed to explore the thermodynamic relationships among the three polymorphs.