Correlation between Molecular Mobility and Physical Stability in Pharmaceutical Glasses

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,...

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Bibliographic Details
Published in:Molecular pharmaceutics 2016-04, Vol.13 (4), p.1267-1277
Main Authors: Mehta, Mehak, Ragoonanan, Vishard, McKenna, Gregory B, Suryanarayanan, Raj
Format: Article
Language:English
Subjects:
Calorimetry, Differential Scanning
Celecoxib - chemistry
Crystallization
Dielectric Spectroscopy
Glass - chemistry
Indomethacin - chemistry
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Summary: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.
ISSN:1543-8384
1543-8392
DOI:10.1021/acs.molpharmaceut.5b00853