Pharmaceutical Research

, Volume 30, Issue 1, pp 280–289 | Cite as

Exploring the Solid-Form Landscape of Pharmaceutical Hydrates: Transformation Pathways of the Sodium Naproxen Anhydrate-Hydrate System

  • Dhara Raijada
  • Andrew D. Bond
  • Flemming H. Larsen
  • Claus Cornett
  • Haiyan Qu
  • Jukka RantanenEmail author
Research Paper



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.


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 13C CP/MAS spectroscopy.


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.


The properties of the polymorphic dihydrate control the transformation pathways of sodium naproxen.


dynamic vapour sorption hydrates sodium naproxen solid-state NMR spectroscopy 



We thank the Danish Natural Sciences Research Council for provision of the X-ray equipment at University of Southern Denmark, Odense. The Lundbeck Foundation (grant numbers 479/06 and R31-A2630) and Department of Pharmacy, University of Copenhagen are also acknowledged for financial support. Support from the Danish Council for Independent Research (Technology and Production Sciences, Project number: 09–066411) is also acknowledged. AstraZeneca (Lund, Sweden) is acknowledged for donation of the DVS instrument.

Supplementary material

11095_2012_872_MOESM1_ESM.doc (1.7 mb)
Esm 1 (DOC 1.66 mb)


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Dhara Raijada
    • 1
  • Andrew D. Bond
    • 2
  • Flemming H. Larsen
    • 3
  • Claus Cornett
    • 1
  • Haiyan Qu
    • 4
  • Jukka Rantanen
    • 1
    Email author
  1. 1.Department of Pharmacy, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
  2. 2.Department of Physics, Chemistry and PharmacyUniversity of Southern DenmarkOdenseDenmark
  3. 3.Department of Food Science, Faculty of Life SciencesUniversity of CopenhagenFrederiksberg CDenmark
  4. 4.Institute of Chemical Engineering, Biotechnology and Environmental TechnologyUniversity of Southern DenmarkOdenseDenmark

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