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Evidence for a New Crystalline Phase of Racemic Ibuprofen

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Abstract

Purpose

The aim of this work is to search for the existence of crystalline polymorphism for racemic Ibuprofen.

Methods

The pharmaceutical material was studied by X-ray diffraction to identify crystalline phases, and by Differential Scanning Calorimetry to follow the thermodynamic evolution of these forms versus temperature.

Results

Results presented here show that, in addition to the already known conventional crystalline phase, whose nucleation domain extends between 233 K and 263 K and which melts at 349 K, racemic Ibuprofen can crystallize in another polymorphic phase. The nucleation of this new polymorphic variety is triggered by a stay at least 60 degrees below the glass transition temperature Tg of Ibuprofen (Tg = 228 K). This nucleation is probably of heterogeneous type. The new phase melts well below the conventional one, i.e. at 290 K. A schematic free energy diagram is provided allowing establishing the relative thermodynamic stability of the two polymorphs.

Conclusions

These results establish, for the first time, that Ibuprofen can exist under two different crystalline phases which constitute a monotropic system, the new form being metastable.

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Acknowledgments

This work is supported by the Hubert Curien partnership PESSOA grant. Region Nord/Pas de Calais and an INTERREG (FEDER) grant helped in providing X-ray equipment.

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Authors and Affiliations

  1. Laboratoire de Dynamique et Structure des Matériaux Moléculaires, UMR CNRS 8024, ERT 1066, Université des Sciences et Technologies de Lille, F-59655, Villeneuve d’Ascq Cedex, France

    Emeline Dudognon, Florence Danède & Marc Descamps

  2. REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516, Caparica, Portugal

    Natália T. Correia

Authors
  1. Emeline Dudognon
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  2. Florence Danède
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  3. Marc Descamps
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  4. Natália T. Correia
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Correspondence to Emeline Dudognon.

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Dudognon, E., Danède, F., Descamps, M. et al. Evidence for a New Crystalline Phase of Racemic Ibuprofen. Pharm Res 25, 2853–2858 (2008). https://doi.org/10.1007/s11095-008-9655-7

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  • DOI: https://doi.org/10.1007/s11095-008-9655-7

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