title: Exploring the solid-form landscape of pharmaceutical hydrates: transformation pathways of the sodium naproxen anhydrate-hydrate system.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark.
authors.forename: Dhara
authors.initials: D
authors.lastname: Raijada
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Bond
authors.forename: Flemming H
authors.initials: FH
authors.lastname: Larsen
authors.forename: Claus
authors.initials: C
authors.lastname: Cornett
authors.forename: Haiyan
authors.initials: H
authors.lastname: Qu
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D003460:Crystallization; D006813:Humidity; D009288:Naproxen / Q000737:chemistry*; D033362:Powder Diffraction; D012964:Sodium / Q000737:chemistry; D013696:Temperature; D013818:Thermogravimetry; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014867:Water; D009288:Naproxen; D012964:Sodium