Correlation between Molecular Mobility and Physical Stability in Pharmaceutical Glasses

Mehak Mehta, Vishard Ragoonanan, Gregory B. McKenna, Raj Suryanarayanan

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


We investigated a possible correlation between molecular mobility and physical stability in glassy celecoxib and indomethacin and identified the specific mobility mode responsible for physical instability (crystallization). In the glassy state, because the structural relaxation times are very long, the measurement was enabled by time domain dielectric spectroscopy. However, the local motions in the glassy state were characterized by frequency domain dielectric spectroscopy. Isothermal crystallization was monitored by powder X-ray diffractometry using either a laboratory source (supercooled state) or synchrotron source (glassy state). Structural (α) relaxation time correlated well with characteristic crystallization time in the supercooled state. On the other hand, a stronger correlation was observed between the Johari-Goldstein (β) relaxation time and physical instability in the glassy state but not with structural relaxation time. These results suggest that Johari-Goldstein relaxation is a potential predictor of physical instability in the glassy state of these model systems.

Original languageEnglish (US)
Pages (from-to)1267-1277
Number of pages11
JournalMolecular pharmaceutics
Issue number4
StatePublished - Apr 4 2016

Bibliographical note

Funding Information:
M.M. was partially supported by the Center for Pharmaceutical Processing and Research and Doctoral Dissertation Fellowship, University of Minnesota. The project was partially funded by the William and Mildred Peters endowment fund. The XRD studies were carried out at the College of Science and Engineering Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. Dr. Sunny Bhardwaj is thanked for helpful discussions and Karlis Be.rzin.s.for helping with data analyses. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.

Publisher Copyright:
© 2016 American Chemical Society.


  • Johari-Goldstein
  • amorphous
  • celecoxib
  • crystallization
  • dielectric spectroscopy
  • glassy
  • indomethacin
  • structural relaxation


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