Understanding Crystal Structures to Guide Form Selection of Active Pharmaceutical Ingredients: A Case Study of AZD9567

AZD9567 is a novel oral selective glucocorticoid receptor modulator drug candidate in AstraZeneca’s pipeline. Three distinctive solid forms of AZD9567 were identified during early development where Form A was found to be a hydrate, and both Forms B and C are anhydrous. In this study, we present the significance of applying crystal structure assessments along with typical solid-state experimental characterizations in early stage drug development to guide solid form selection. The Form A hydrate, which is usually regarded as the preferred form in liquid formulation, is found not stable, narrowing the form selection toward Forms B and C. Anhydrous Form C has disorder depending on the temperature and is more stable than anhydrous Form B, and this is supported by a higher melting point and experimental density as well as a series of density functional theory calculations. This eventually results in the recommendation of selecting anhydrous AZD9567 Form C as the solid form to move forward for further development.