Influence of Molecular Mobility on the Physical Stability
of Amorphous Pharmaceuticals in the Supercooled and Glassy States
- Publication date
- Publisher
Abstract
We investigated the correlation between
molecular mobility and
physical stability in three model systems, including griseofulvin,
nifedipine, and nifedipine–polyvinylpyrrolidone dispersion,
and identified the specific mobility mode responsible for instability.
The molecular mobility in the glassy as well as the supercooled liquid
states of the model systems were comprehensively characterized using
dynamic dielectric spectroscopy. Crystallization kinetics was monitored
by powder X-ray diffractometry using either a laboratory (in the supercooled
state) or a synchrotron (glassy) X-ray source. Structural (α-)
relaxation appeared to be the mobility responsible for the observed
physical instability at temperatures above <i>T</i><sub>g</sub>. Although the direct measurement of the structural relaxation
time below <i>T</i><sub>g</sub> was not experimentally feasible,
dielectric measurements in the supercooled state were used to provide
an estimate of the α-relaxation times as a function of temperature
in glassy pharmaceuticals. Again, there was a strong correlation between
the α-relaxation and physical instability (crystallization)
in the glassy state but not with any secondary relaxations. These
results suggest that structural relaxation is a major contributor
to physical instability both above and below <i>T</i><sub>g</sub> in these model systems