Multicomponent Salts of the Antidiabetic Agent Saxagliptin: Hydration-Assisted Assembly and Lipophilic Aggregation with Carboxylic Acids

We report the formation of five new salts of saxagliptin (SAX, trade name: Onglyza), an active pharmaceutical ingredient (API) approved by the FDA for the treatment of type II diabetes mellitus. Salt formation is achieved by exploiting the ability of SAX to accept a proton from five pharmacologically acceptable carboxylic acids, isonicotinic, adipic, succinic, salicylic, and 5-sulfosalicylic acids, resulting in charge-assisted hydrogen bonds between the protonated amine of SAX and the carboxylate or sulfonate anion. Hydration is prevalent in four of the five multicomponent solids, contributing to the stabilization of distinct supramolecular architectures. The crystal structures determined by single-crystal X-ray diffraction are further supported by thermal analysis, Fourier transform infrared spectroscopy, and molecular modeling. This work provides design elements for developing multicomponent salts of SAX and related lipophilic, adamantane-bearing APIs.