Mechanism of Dehydration–Hydration Processes of Lisinopril Dihydrate Investigated by ab Initio Powder X‑ray Diffraction Analysis

Lisinopril is extensively used as an ethical anti-hypertensive
drug in its dihydrate crystalline phase, where this phase undergoes
dehydration to the metastable monohydrate and anhydrous phases upon
being heated. The mechanistic aspects of this two-step dehydration
process are successfully established from their crystal structures,
determined for the first time by ab initio powder X-ray diffraction
(PXRD) analysis. Furthermore, the hydration process of the anhydrous
phase was investigated by humidity-controlled PXRD and dynamic vapor
sorption. Although the dehydration process of the dihydrate phase
proceeded in two steps via the metastable monohydrate phase, the hydration
process from the anhydrous phase to the dihydrate phase proceeded
in a single step. The mechanisms of these different pathways for the
dehydration and hydration processes were also established from the
crystal structures.