Abstract
Purpose
To clarify the polymorphism of racemic Ibuprofen and to determine the kinetic of the phase transformation that follows crystallisation of phase II.
Methods
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.
Results
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.
Conclusions
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.
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References
Brittain HG. Polymorphism in pharmaceutical solids. Drugs and the pharmaceutical sciences vol. 95. New York: Marcel Dekker; 1999.
Bernstein J. Polymorphism in molecular crystals. Oxford: Oxford Science; 2002.
Hilfiker R. Polymorphism in the pharmaceutical industry. Weiheim: Wiley-VCH; 2006.
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.
McConnell JF. 2-(4-isobuthylphenyl) propionic acid. C13 H18 O2 ibuprofen or prufen. Cryst Struct Comm. 1974;3:73–5.
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.
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.
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.
Dudognon E, Danède F, Descamps M, Correia NT. Evidence for a new crystalline phase of racemic ibuprofen. Pharm Res. 2008;25(12):2853–8.
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.
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.
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.
Paladi F, Oguni M. Anomalous generation and extinction of crystal nuclei in nonequilibrium supercooled liquid o-benzylphenol. Phys Rev B. 2002;65:144202.
Burger A, Ramberger R. On the polymorphism of pharmaceuticals and other molecular crystals. I. Theory of thermodynamic rules. Mikrochimica Acta II. 1979:259–271.
Burger A, Ramberger R. On the polymorphism of pharmaceuticals and other molecular crystals. II. Applicability of thermodynamic rules. Mikrochimica Acta II. 1979:273–316.
Ostwald W. Studien über die Bildung und Umwandlung fester Körper. 1. Abhandlung: Übersättigung und Überkaltung. Z Phys Chem. 1897;22:289–330.
Threlfall T. Structural and thermodynamic explanations of Ostwald’s rule. Org Process Res Dev. 2003;7:1017–27.
Kitaigorodskiy AI, Mnyukh YV, Asadov YG. Relationships for single crystal growth during polymorphic transformation. J Phys Chem Solids. 1965;26:463–72.
Avrami M. Kinetics of phase change. I* general theory. J Chem Phys. 1939;7:1103–12.
Avrami M. Kinetics of phase change. II transformation-time relations for random distribution of nuclei. J Chem Phys. 1940;8:212–24.
Avrami M. Granulation, phase change, and microstructure kinetics of phase change. III*. J Chem Phys. 1941;9:177–84.
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.
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.
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Dudognon, E., Correia, N.T., Danède, F. et al. Solid-Solid Transformation in Racemic Ibuprofen. Pharm Res 30, 81–89 (2013). https://doi.org/10.1007/s11095-012-0851-0
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DOI: https://doi.org/10.1007/s11095-012-0851-0