Two Novel Pharmaceutical Cocrystals of a Development Compound – Screening, Scale-up, and Characterization

A streamlined methodology for cocrystal screening and scale-up has been developed. There are two parts to this procedure: (1) a high throughput screening approach for the rapid identification of potential cocrystal leads and (2) a new procedure for solvent selection, rapidly mapping the critical region in the ternary phase diagram, and determining a cocrystallization procedure for scale-up. Using this approach, we have discovered and scaled-up two new cocrystal forms of the pharmaceutically active compound 1 for the treatment of type II diabetes. This approach provided more than 2 g of cocrystal material suitable for biopharmaceutical evaluation. The physicochemical characterization and single crystal X-ray diffraction data of these cocrystals are also presented and discussed.