Pharmaceutical Research

, Volume 29, Issue 9, pp 2489–2498 | Cite as

Effect of Compression on Non-isothermal Crystallization Behaviour of Amorphous Indomethacin

  • Zelalem Ayenew
  • Amrit Paudel
  • Patrick Rombaut
  • Guy Van den Mooter
Research Paper



To evaluate the effect of tablet compression on the physical stability of amorphous indomethacin.


The amorphous indomethacin generated by melt cooling, rapid (5°C/min) or slow (0.2°C/min) cooling, was evaluated by PXRD, mDSC and FTIR analysis. Non-isothermal crystallisation behaviour was assessed using mDSC and any structural changes with compression were monitored by FTIR. Amorphous indomethacin was compressed in a DSC pan using a custom made die cavity-punch setup and further analysed in the primary container to minimize stress due to sample transfer and preparation.


Compression of amorphous indomethacin induced and increased the extent of crystallisation upon heating. DSC results revealed that amorphous indomethacin generated by rapid cooling is more prone to compression induced crystallisation than the slowly cooled one. Onset temperature for crystallisation (T c ) of uncompressed slowly and rapidly cooled samples are 121.4 and 124°C and after compression T c decreased to ca 109 and ca 113°C, respectively. Compression of non-aged samples led to higher extent of crystallisation predominantly into γ-form. Aging followed by compression led to crystallisation of mainly the α-form.


Compression affects the physical stability of amorphous indomethacin. Structural changes originated from tablet compression should be duly investigated for the stable amorphous formulation development.


amorphous compression crystallisation indomethacin relaxation 



dwell time


Fourier transform infrared spectroscopy (Attenuated total reflectance)




modulated differential scanning calorimetry


poly(methyl methacrylate)


powder x-ray diffraction


onset temperature for crystallisation


glass transition temperature


thermally stimulated depolarization current spectroscopy


heat capacity change


heat of crystallization


melting enthalpy of α-form


melting enthalpy of γ-form


enthalpy recovery



ZA is grateful for the financial support of IRO, KU Leuven. AP also acknowledges D.B.O.F., KU Leuven, for providing a PhD grant. Department of Metallurgy and Materials Engineering (MTM), KU Leuven is also greatly acknowledged for providing facility for the ATR-FTIR.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Zelalem Ayenew
    • 1
  • Amrit Paudel
    • 1
  • Patrick Rombaut
    • 1
  • Guy Van den Mooter
    • 1
  1. 1.Laboratory for Pharmacotechnology and BiopharmacyKU LeuvenLeuvenBelgium

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