Journal
CRYSTAL GROWTH & DESIGN
Volume 12, Issue 12, Pages 6165-6172Publisher
AMER CHEMICAL SOC
DOI: 10.1021/cg3013377
Keywords
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Funding
- JST
- CREST
- Ministry of Education, Culture, Sports, Science and Technology of Japan
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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.
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