A peculiar dehydration and solid–solid phase transition of the active pharmaceutical ingredient AZD9898 based on in situ single crystal-to-single crystal transformations

Abstract

AZD9898 has previously been used as a candidate for a potentially active pharmaceutical ingredient. AZD9898 form A hydrate was discovered during development and this form undergoes dehydration upon heating to give anhydrous form B. Further heating results in a solid–solid phase transition to a new anhydrous phase, form C. This study reports the crystal structures of form A, B, and C obtained by heating the single crystal of form A in situ on the diffractometer which establish the dehydration and solid–solid phase transition mechanisms. The dehydration from form A hydrate to form B anhydrous is an isostructural process while the solid–solid phase transition from form B to form C requires major structural changes. The relevant thermal profiles and vapour sorption behaviour of these forms are also reported in this study.