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Pharm Res. 2012 Sep;29(9):2489-98. doi: 10.1007/s11095-012-0778-5. Epub 2012 May 26.

Effect of compression on non-isothermal crystallization behaviour of amorphous indomethacin.

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Laboratory for Pharmacotechnology and Biopharmacy, KU Leuven, Herestraat 49, bus 921, 3000 Leuven, Belgium.



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.

[Indexed for MEDLINE]

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