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 Rantanen
Research Paper

ABSTRACT

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 13C 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.

KEY WORDS

dynamic vapour sorption hydrates sodium naproxen solid-state NMR spectroscopy 

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

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)

REFERENCES

  1. 1.
    Debnath S, Suryanarayanan R. Influence of processing-induced phase transformations on the dissolution of theophylline tablets. AAPS PharmSciTech. 2004;5(1):E8. Epub 2004/06/17.Google Scholar
  2. 2.
    Khankari RK, Grant DJW. Pharmaceutical hydrates. Thermochim Acta. 1995;248:61–79.CrossRefGoogle Scholar
  3. 3.
    Malaj L, Censi R, Gashi Z, Di Martino P. Compression behaviour of anhydrous and hydrate forms of sodium naproxen. Int J Pharm. 2010;390(2):142–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Phadnis NV, Suryanarayanan R. Polymorphism in anhydrous theophylline—implications on the dissolution rate of theophylline tablets. J Pharm Sci. 1997;86(11):1256–63.PubMedCrossRefGoogle Scholar
  5. 5.
    Zhang GGZ, Law D, Schmitt EA, Qiu Y. Phase transformation considerations during process development and manufacture of solid oral dosage forms. Adv Drug Delivery Rev. 2004;56(3):371–90.CrossRefGoogle Scholar
  6. 6.
    Reutzel-Edens SM, Bush JK, Magee PA, Stephenson GA, Byrn SR. Anhydrates and hydrates of olanzapine: crystallization, solid-state characterization, and structural relationships. Cryst Growth Des. 2003;3(6):897–907.CrossRefGoogle Scholar
  7. 7.
    Dong Z, Padden BE, Salsbury JS, Munson EJ, Schroeder SA, Prakash I, et al. Neotame anhydrate polymorphs I: preparation and characterization. Pharm Res. 2002;19(3):330–6.CrossRefGoogle Scholar
  8. 8.
    Tian F, Rantanen J. Perspective on water of crystallization affecting the functionality of pharmaceuticals. Food Biophys. 2011;6(2):250–8.CrossRefGoogle Scholar
  9. 9.
    Van Tonder EC, Maleka TSP, Liebenberg W, Song M, Wurster DE, de Villiers MM. Preparation and physicochemical properties of niclosamide anhydrate and two monohydrates. Int J Pharm. 2004;269(2):417–32.PubMedCrossRefGoogle Scholar
  10. 10.
    Griesser UJ, Burger A. The effect of water vapor pressure on desolvation kinetics of caffeine 4/5-hydrate. Int J Pharm. 1995;120(1):83–93.CrossRefGoogle Scholar
  11. 11.
    Chen LR, Young Jr VG, Lechuga-Ballesteros D, Grant DJW. Solid-state behavior of cromolyn sodium hydrates. J Pharm Sci. 1999;88(11):1191–200.PubMedCrossRefGoogle Scholar
  12. 12.
    Gillon AL, Davey RJ, Storey R, Feeder N, Nichols G, Dent G, et al. Solid state dehydration processes: mechanism of water loss from crystalline inosine dihydrate. J Phys Chem B. 2005;109(11):5341–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Tian F, Qu H, Louhi-Kultanen M, Rantanen J. Mechanistic insight into the evaporative crystallization of two polymorphs of nitrofurantoin monohydrate. J Cryst Growth. 2009;311(8):2580–9.CrossRefGoogle Scholar
  14. 14.
    Brittain HG. Polymorphism and solvatomorphism 2010. J Pharm Sci. 2012;101(2):464–84.PubMedCrossRefGoogle Scholar
  15. 15.
    Braun DE, Tocher DA, Price SL, Griesser UJ. The complexity of hydration of phloroglucinol: a comprehensive structural and thermodynamic characterization. J Phys Chem B. 2012;116(13):3961–72.PubMedCrossRefGoogle Scholar
  16. 16.
    Wikström H, Rantanen J, Gift AD, Taylor LS. Toward an understanding of the factors influencing anhydrate-to-hydrate transformation kinetics in aqueous environments. Cryst Growth Des. 2008;8(8):2684–93.CrossRefGoogle Scholar
  17. 17.
    Varughese S, Desiraju GR. Using water as a design element in crystal engineering. Host−guest compounds of hydrated 3,5-dihydroxybenzoic acid. Cryst Growth Des. 2010;10(9):4184–96.CrossRefGoogle Scholar
  18. 18.
    Clarke HD, Arora KK, Wojtas Ł, Zaworotko MJ. Polymorphism in multiple component crystals: Forms III and IV of gallic acid monohydrate. Cryst Growth Des. 2011;11(4):964–6.CrossRefGoogle Scholar
  19. 19.
    Di Martino P, Barthélémy C, Palmieri GF, Martelli S. Physical characterization of naproxen sodium hydrate and anhydrate forms. Eur J Pharm Sci. 2001;14(4):293–300.PubMedCrossRefGoogle Scholar
  20. 20.
    Kim Y-S, Rousseau RW. Characterization and solid-state transformations of the pseudopolymorphic forms of sodium naproxen. Cryst Growth Des. 2004;4(6):1211–6.CrossRefGoogle Scholar
  21. 21.
    Malaj L, Censi R, Martino PD. Mechanisms for dehydration of three sodium naproxen hydrates. Cryst Growth Des. 2009;9(5):2128–36.CrossRefGoogle Scholar
  22. 22.
    Martino PD, Barthélémy C, Joiris E, Capsoni D, Masic A, Massarotti V, et al. A new tetrahydrated form of sodium naproxen. J Pharm Sci. 2007;96(1):156–67.PubMedCrossRefGoogle Scholar
  23. 23.
    Feth MP, Nagel N, Baumgartner B, Bröckelmann M, Rigal D, Otto B, et al. Challenges in the development of hydrate phases as active pharmaceutical ingredients – An example. Eur J Pharm Sci. 2011;42(1–2):116–29.PubMedCrossRefGoogle Scholar
  24. 24.
    Gift AD, Taylor LS. Hyphenation of Raman spectroscopy with gravimetric analysis to interrogate water–solid interactions in pharmaceutical systems. J Pharm Biomed Anal. 2007;43(1):14–23.PubMedCrossRefGoogle Scholar
  25. 25.
    Lane RA, Buckton G. The novel combination of dynamic vapour sorption gravimetric analysis and near infra-red spectroscopy as a hyphenated technique. Int J Pharm. 2000;207(1–2):49–56.PubMedCrossRefGoogle Scholar
  26. 26.
    Feth MP, Jurascheck J, Spitzenberg M, Dillenz J, Bertele G, Stark H. New technology for the investigation of water vapor sorption–induced crystallographic form transformations of chemical compounds: a water vapor sorption gravimetry–dispersive raman spectroscopy coupling. J Pharm Sci. 2011;100(3):1080–92.PubMedCrossRefGoogle Scholar
  27. 27.
    Bennett AE, Rienstra CM, Auger M, Lakshmi KV, Griffin RG. Heteronuclear decoupling in rotating solids. J Chem Phys. 1995;103(16):6951–8.CrossRefGoogle Scholar
  28. 28.
    Peersen OB, Wu XL, Kustanovich I, Smith SO. Variable-amplitude cross-polarization MAS NMR. J Magn Reson, Ser A. 1993;104(3):334–9.CrossRefGoogle Scholar
  29. 29.
    Ando S, Kikuchi J, Fujimura Y, Ida Y, Higashi K, Moribe K, et al. Physicochemical characterization and structural evaluation of a specific 2:1 cocrystal of naproxen-nicotinamide. J Pharm Sci. 2012;101(9):3214–21.Google Scholar
  30. 30.
    Kim Y-s, Paskow HC, Rousseau RW. Propagation of solid-state transformations by dehydration and stabilization of pseudopolymorphic crystals of sodium naproxen. Cryst Growth Des. 2005;5(4):1623–32.Google Scholar

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
  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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