RESUMO
INTRODUCTION: Hydrates are often used as pharmaceutical active pharmaceutical ingredients (API), especially when anhydrates may not be feasible likely due to physicochemical properties concerns. Pharmaceutical hydrates, whereas water is present as crystal adduct, are feasible for drug products as they do not pose any safety concern. Hydrates can impart many different advantages; therefore, they are quite common and preferred solid forms for numerous pharmaceutical materials on market. However, hydrates may involve various phase transitions, which may impact the stability and processability of drug substance. METHODS: Phase transitions, which include temperature-induced dehydration and moisture-facilitated rehydration are investigated by different solid-state analytical techniques such as powder x-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, polarized light microscopy, and single-crystal x-ray diffraction. RESULTS: This research investigation focuses on the different phase transition behaviors of a newly discovered pharmaceutical compound with three channel hydrates, two of which confirmed by single-crystal analysis. The retention or rearrangement of crystal structures over the transitions are studied. Hydrate 3 exhibits a characteristic feature of channel hydrate that involves symmetric lattice relaxation. Unlike hydrate 3, hydrate 2 results in a potentially new unit cell upon dehydration due to asymmetric lattice relaxation, which converted back to Hydrate 2 in presence of water, a very unique behavior for a channel hydrate, rarely observed, which entails novelty of this research work. CONCLUSION: The relationship among crystal forms of different hydrates of this new compound is thus established. The current investigation is a vital part of drug product risk assessment for hydrates to avoid any challenges during manufacturing operations and/or stability studies. This investigation was successfully applied in the present study and can be expanded to other newly discovered APIs in future.