Pharmaceutical Research

, Volume 30, Issue 1, pp 81–89 | Cite as

Solid-Solid Transformation in Racemic Ibuprofen

  • Emeline Dudognon
  • Natália T. Correia
  • Florence Danède
  • Marc Descamps
Research Paper



To clarify the polymorphism of racemic Ibuprofen and to determine the kinetic of the phase transformation that follows crystallisation of phase II.


Differential Scanning Calorimetry (DSC), X-ray powder diffraction and Hot Stage Microscopy are complementarily used to perform a kinetic investigation of the particular temperature range where competition between the occurrence of phases I and II is suspected.


Experiments performed with the three techniques reveal that at 273 K the crystallisation to phase II is then followed by a solid-solid transition towards phase I. This transformation is exothermic (conversion enthalpy of 8.0 ± 0.5 kJ/mol), which proves that the two phases form a monotropic set. The kinetics of conversion deduced from X-Ray experiments follows a Johnson-Mehl-Avrami equation and the Hot Stage Microscopy allows us to establish that the transformation proceeds by the growth of some nuclei of phase I probably formed at lower temperature.


These results allow us to precise the stability pattern of racemic Ibuprofen and to establish the kinetic conditions of appearance and interconversion of the different phases. Therefore such real time resolved investigations would help if applied in the screening of polymorphs when competitive crystallisations occur.


ibuprofen monotropic solid-solid transition 


Acknowledgments and Disclosures

Financial support to Fundação para a Ciência e Tecnologia (FCT, Portugal) through the project PTDC/CTM/098979/2008 is acknowledged. This work was also supported by the interreg IV “2 mers seas zeeën” cross-border cooperation programme 2007–2013.


  1. 1.
    Brittain HG. Polymorphism in pharmaceutical solids. Drugs and the pharmaceutical sciences vol. 95. New York: Marcel Dekker; 1999.Google Scholar
  2. 2.
    Bernstein J. Polymorphism in molecular crystals. Oxford: Oxford Science; 2002.Google Scholar
  3. 3.
    Hilfiker R. Polymorphism in the pharmaceutical industry. Weiheim: Wiley-VCH; 2006.Google Scholar
  4. 4.
    Xu F, Sun LX, Tan ZC, Liang JG, Li RL. Thermodynamic study of ibuprofen by adiabatic calorimetry and thermal analysis. Thermochim Acta. 2004;412:33–7.CrossRefGoogle Scholar
  5. 5.
    McConnell JF. 2-(4-isobuthylphenyl) propionic acid. C13 H18 O2 ibuprofen or prufen. Cryst Struct Comm. 1974;3:73–5.Google Scholar
  6. 6.
    Shankland N, Wilson CC, Florence AJ, Cox PJ. Refinement of ibuprofen at 100 K by single-crystal pulsed neutron diffraction. Acta Crystallogr. 1997;C53:951–4.Google Scholar
  7. 7.
    Brás AR, Noronha JP, Antunes AMM, Cardoso MM, Schönhals A, Affouard F, Dionisio M, Correia NT. Molecular motions in amorphous ibuprofen as studied by broadband dielectric spectroscopy. J Phys Chem B. 2008;112:11087–99.PubMedCrossRefGoogle Scholar
  8. 8.
    Johari GP, Kim S, Shanker RM. Dielectric relaxation and crystallization of ultraviscous melt and glassy states of aspirin, ibuprofen, progesterone, and quinidine. J Pharm Sci. 2007;96:1159–75.PubMedCrossRefGoogle Scholar
  9. 9.
    Dudognon E, Danède F, Descamps M, Correia NT. Evidence for a new crystalline phase of racemic ibuprofen. Pharm Res. 2008;25(12):2853–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Derollez P, Dudognon E, Affouard F, Danède F, Correia NT, Descamps M. Ab initio structure determination of phase II of racemic ibuprofen by X-ray powder diffraction. Acta Crystallogr. 2010;B66:76–80.Google Scholar
  11. 11.
    Legrand V, Descamps M, Alba-Simionesco C. Glass-forming meta-toluidine: a thermal and structural analysis of its crystalline polymorphism and devitrification. Thermochim Acta. 1997;307:77–83.CrossRefGoogle Scholar
  12. 12.
    Paladi F, Oguni M. Generation and extinction of crystal nuclei in an extremely non-equilibrium glassy state of salol. J Phys Condens Matter. 2003;15:3909–17.CrossRefGoogle Scholar
  13. 13.
    Paladi F, Oguni M. Anomalous generation and extinction of crystal nuclei in nonequilibrium supercooled liquid o-benzylphenol. Phys Rev B. 2002;65:144202.CrossRefGoogle Scholar
  14. 14.
    Burger A, Ramberger R. On the polymorphism of pharmaceuticals and other molecular crystals. I. Theory of thermodynamic rules. Mikrochimica Acta II. 1979:259–271.Google Scholar
  15. 15.
    Burger A, Ramberger R. On the polymorphism of pharmaceuticals and other molecular crystals. II. Applicability of thermodynamic rules. Mikrochimica Acta II. 1979:273–316.Google Scholar
  16. 16.
    Ostwald W. Studien über die Bildung und Umwandlung fester Körper. 1. Abhandlung: Übersättigung und Überkaltung. Z Phys Chem. 1897;22:289–330.Google Scholar
  17. 17.
    Threlfall T. Structural and thermodynamic explanations of Ostwald’s rule. Org Process Res Dev. 2003;7:1017–27.CrossRefGoogle Scholar
  18. 18.
    Kitaigorodskiy AI, Mnyukh YV, Asadov YG. Relationships for single crystal growth during polymorphic transformation. J Phys Chem Solids. 1965;26:463–72.CrossRefGoogle Scholar
  19. 19.
    Avrami M. Kinetics of phase change. I* general theory. J Chem Phys. 1939;7:1103–12.CrossRefGoogle Scholar
  20. 20.
    Avrami M. Kinetics of phase change. II transformation-time relations for random distribution of nuclei. J Chem Phys. 1940;8:212–24.CrossRefGoogle Scholar
  21. 21.
    Avrami M. Granulation, phase change, and microstructure kinetics of phase change. III*. J Chem Phys. 1941;9:177–84.CrossRefGoogle Scholar
  22. 22.
    Woldt E. The relationship between isothermal and non-isothermal description of Johnson-Mehl-Avrami-Kolmogorov kinetics. J Phys Chem Solids. 1992;53(4):521–7.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Emeline Dudognon
    • 1
  • Natália T. Correia
    • 1
    • 2
  • Florence Danède
    • 1
  • Marc Descamps
    • 1
  1. 1.Unité Matériaux Et Transformations, UMR CNRS 8207Université Lille Nord de FranceVilleneuve d’Ascq CedexFrance
  2. 2.REQUIMTE, Departamento de Química Faculdade de Ciências e TecnologiaUniversidade Nova de LisboaCaparicaPortugal

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