Enhanced Solubility of Famotidine through Salification

Famotidine (FMT) is an active pharmaceutical ingredient that exhibits poor aqueous solubility and poor permeability. Molecular electrostatic potential and pK _a calculations were used to guide a salification strategy for FMT and afforded five salts featuring carboxylic acid-containing coformers. All solids feature charge-assisted hydrogen bonds between the guanidinium group of FMT and carboxylate of the coformer. All salts exhibited good thermal and benchtop stability, and a six- to 20-fold increase in aqueous solubility was achieved, depending on the coformer used. The best performing salts include coformers on the FDA's generally recognized as safe list, making the solids promising for pharmaceutical applications.