Pharmaceutical Research

, Volume 12, Issue 6, pp 799–806

Molecular Mobility of Amorphous Pharmaceutical Solids Below Their Glass Transition Temperatures

  • Bruno C. Hancock
  • Sheri L. Shamblin
  • George Zografi
Article

DOI: 10.1023/A:1016292416526

Cite this article as:
Hancock, B.C., Shamblin, S.L. & Zografi, G. Pharm Res (1995) 12: 799. doi:10.1023/A:1016292416526

Abstract

Purpose. To measure the molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures (Tg), using indomethacin, poly (vinyl pyrrolidone) (PVP) and sucrose as model compounds.

Methods. Differential scanning calorimetry (DSC) was used to measure enthalpic relaxation of the amorphous samples after storage at temperatures 16-47 K below Tg for various time periods. The measured enthalpy changes were used to calculate molecular relaxation time parameters. Analogous changes in specimen dimensions were measured for PVP films using thermomechanical analysis.

Results. For all the model materials it was necessary to cool to at least 50 K below the experimental Tg before the molecular motions detected by DSC could be considered to be negligible over the lifetime of a typical pharmaceutical product. In each case the temperature dependence of the molecular motions below Tg was less than that typically reported above Tg and was rapidly changing.

Conclusions. In the temperature range studied the model amorphous solids were in a transition zone between regions of very high molecular mobility above Tg and very low molecular mobility much further below Tg. In general glassy pharmaceutical solids should be expected to experience significant molecular mobility at temperatures up to fifty degrees below their glass transition temperature.

amorphousglass transition temperatureagingmolecular mobilityrelaxation time

Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Bruno C. Hancock
    • 1
  • Sheri L. Shamblin
    • 1
  • George Zografi
    • 1
  1. 1.School of PharmacyUniversity of Wisconsin-MadisonMadison
  2. 2.Merck-Frosst Canada Inc.QuebecCanada