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Updated: May 18, 2026

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Published on: August 9, 2022
Exploring the solid-form landscape of pharmaceutical hydrates: transformation pathways of the sodium naproxen
Dhara Raijada1, Andrew D Bond, Flemming H Larsen
1Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark.
Purpose:
To understand the transformation pathways amongst anhydrate/hydrate solid forms of sodium naproxen and to highlight the importance of a polymorphic dihydrate within this context.
Methods:
Multi-temperature dynamic vapour sorption (DVS) analysis combined with variable-humidity X-ray powder diffraction (XRPD) to establish the transformation pathways as a function of temperature and humidity. XRPD and thermogravimetric analysis (TGA) to characterise bulk samples. Monitoring of in-situ dehydration using solid-state (13)C CP/MAS spectroscopy.
Results:
At 25 °C, anhydrous sodium naproxen (AH) transforms directly to one dihydrate polymorph (DH-II). At 50 °C, AH transforms stepwise to a monohydrate (MH) then to the other dihydrate polymorph (DH-I). DH-II transforms to a tetrahydrate (TH) more readily than DH-I transforms to TH. Both dihydrate polymorphs transform to the same MH.
Conclusions:
The properties of the polymorphic dihydrate control the transformation pathways of sodium naproxen.
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