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

ABSTRACT

Purpose

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

Methods

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.

Results

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.

Conclusions

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

KEY WORDS

amorphous compression crystallisation indomethacin relaxation 

ABBREVIATIONS

DT

dwell time

FTIR (ATR)

Fourier transform infrared spectroscopy (Attenuated total reflectance)

m

minute

mDSC

modulated differential scanning calorimetry

PMMA

poly(methyl methacrylate)

PXRD

powder x-ray diffraction

Tc

onset temperature for crystallisation

Tg

glass transition temperature

TSDC

thermally stimulated depolarization current spectroscopy

ΔCp

heat capacity change

ΔHc

heat of crystallization

ΔHf(α)

melting enthalpy of α-form

ΔHf(γ)

melting enthalpy of γ-form

ΔHrec

enthalpy recovery

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

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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