Supplementary file Pharmaceutical Research
Exploring the solid-form landscape of pharmaceutical hydrates: Transformation pathways of the sodium naproxen anhydrate-hydrate system
Dhara Raijada,1 Andrew D. Bond,2 Flemming H. Larsen,3 Claus Cornett,1 Haiyan Qu,4 Jukka Rantanen1,5
1 Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
2 Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5230 Odense, Denmark
3 Department of Food Science, Faculty of Life Sciences, University of Copenhagen, 1958 Frederiksberg C, Denmark
4 Institute of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, 5230 Odense, Denmark
5 To whom correspondence should be addressed (University of Copenhagen, Faculty of Health and Medical Sciences, Department of Pharmacy, Universitetsparken 2, 2100 Copenhagen, Denmark, Tel: +4535336585, Fax: +4535336030, Email: )
Supplementary Information
Supplementary Section A. Dynamic vapour sorption analysis at various temperatures
Supplementary Fig. 1.DVS traces at (a) 30°C,(b) 35°C, (c) 40°C, and, (d) 45°C.
Supplementary Section B. XRPD patterns under static RH conditions
Supplementary Fig. 2. (a). XRPD patterns from an AH sample under static conditions at25 °C/50 % RH. The sample shows no change; (b). XRPD patterns from an AH sample under static conditions at25 °C/55 % RH. The sample transforms directly to DH-II, with no indication of intermediate MH.
Supplementary Section C. Scanning electron microscopy (SEM)
The morphology of sodium naproxen anhydrate-hydrate forms was examined using a JSM-5200 Scanning Electron Microscopy (SEM; JEOL Ltd, Tokyo, Japan). For the same, samples were transferred onto carbon sticky tape and mounted in metal stubs. Sputter coating was performed with a thin layer of gold-palladium for 120 seconds using E5200 Auto Sputter Coater (BIO-RAD, Polaron Equipment Ltd, Watford, England) under Argon gas purge (Air Liquide, Taastrup, Denmark). The samples were then imaged at accelerating voltage of 25kV energy at magnifications of 150X and 1500X.
Supplementary Fig. 3 depicts scanning electron microphotographs for AH, MH, DH-I, DH-II and TH forms. AH and MH shows flat plate-like crystals of somewhat rectangular shape with agglomeration of small plates over big ones. DH-II showed growth of small needles over big plate-like crystals. DH-I and TH showed agglomerated rectangular shaped plate crystals with relatively smooth surface.
Supplementary Fig.3. Scanning electron micro-photographs for NS solid forms
Supplementary Section D: XRPD patterns of dihydrate forms exposed under various conditions
Supplementary Fig. 4. Comparison of dihydrate forms: (a) DH-I, generated by exposure of AH form at 50 °C/80 %RH for 7d and kept at 25 °C/55 % RH for 2 months (stable); (b) DH-II, generated by exposure of AH form at 25 °C/55 % RH for 7d and kept at 50 °C/80 %RH for 7d (transforms to DH-I with broader peak features than the actual DH-I generated by exposure of AH at 50 °C/80 %RH); (c) DH-II, generated by exposure of AH form at 25 °C/55 % RH for 7d and kept at 50 °C/80 %RH for 2m (transforms to mixture of DH+TH); (d) dehydrated DH (mixture of DH-I and DH-II) generated by dehydration of TH under ambient conditions
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