Assessing Structures and Solution Behaviors of Molecular and Ionic Cocrystals with a Common Bioactive Molecule: 2,4-Pyridinedicarboxylic Acid with Tranexamic Acid and Nicotinamide.

Cocrystals of 2,4-pyridinedicarboxylic acid () with either nicotinamide () or tranexamic acid () as ( and , respectively, are reported, with the former being a molecular cocrystal and the latter being an ionic cocrystal. Single-crystal structure analyses showed that and its coformers are sustained by neutral and ionic hydrogen bonds. Suspensions of resulted in complete conversion to monohydrate after 48 h, while was thermodynamically stable at a lower pH and showed a 2-fold increase in the concentration, relative to pure monohydrate under similar conditions. Thermal characterization of displayed a lower melting point and a lower heat of fusion, relative to the pure components. Powder dissolution studies were evaluated for , , and and the corresponding physical mixtures. The percent of dissolved rapidly reached near 100% for most cases; however, for , complete dissolution was not achieved, and the amount of dissolved decreased to 85% after 3 h. Instability of was likely a result of a high solution pH during dissolution, and our results confirm that the solution pH plays a key role in determining the solution behavior and phase stability of the cocrystals.