Chemistry Reference
In-Depth Information
and glasses are spatially heterogeneous and that there are many different types of
molecular motion occurring that will change with both temperature and time
(in particular for glasses). While molecular mobility is much lower in materials stored
below
T
g
, crystallization does indeed occur in glasses. Thus, there are numerous reports
of crystallization of amorphous systems following storage at
temperatures below
T
g
[25
C below
T
g
[28]. Unfortunately, the types of molecular motion important for nucleation in glasses
are not well understood. In addition, it has been observed that the relationship between
bulk molecular diffusion and crystal growth rates also breaks down in glasses [8,9].
Another factor that should be considered is that the temperature dependence of
nucleation and crystal growth rates differs. The maximum in the nucleation rate usually
occurs at a lower temperature than that observed for the growth rate, as shown in
Figure 5.2 [29]. Consequently, it is not currently possible to predict bulk crystallization
kinetics using experimental measurements of molecular mobility, which tend to yield
average values. Although it is not possible to predict long-term stability against
crystallization from measurements of molecular mobility, correlations are frequently
observed between these two factors.
Several studies have investigated the relationship between
-
27], and nucleation has been reported at temperatures as low as 55
°
α
-mobility and crystalli-
zation rates.
-Mobility, which arises from molecular rotation and translation, is
generally associated with larger length scales and is the type of mobility associated
with viscous
α
flow and the glass transition. Aso et al. [30] probed the crystallization rate of
three pharmaceutical compounds (nifedipine, phenobarbital, and
flopropione) and
measured the molecular mobility using
1
H nuclear magnetic resonance (NMR) relaxa-
tion times and enthalpy relaxation experiments. Crystallization rates for phenobarbital
and
flopropione were much lower below
T
g
relative to above
T
g
; in contrast, nifedipine
showed much more modest differences. Relaxation experiments suggested that the
molecular mobility of nifedipine was higher below
T
g
than that of either phenobarbital or
flopropione, leading to faster crystallization kinetics. In another study, the molecular
mobility of indomethacin and nifedipine was compared using
13
C and
1
H NMR [31].
The results showed that nifedipine had higher molecular mobility and lower activation
energy for molecular motion in the glassy state compared with indomethacin, again
correlating with the higher observed crystallization rate for nifedipine. Similar correla-
tions between relaxation rates and crystallization rates were observed for amorphous
indomethacin and salicin by Masuda et al. [32]. Using
13
C NMR, shorter relaxation times
were observed for the more rapidly crystallizing salicin.
Many studies have also been conducted investigating relationships between
β
-mobility, a much faster motion that occurs on shorter length scales, and crystallization.
A study conducted by Alie et al. [33] measured both the
-relaxation processes as
a function of temperature for a model compound using dynamic dielectric spectroscopy,
and correlated the results with the observed characteristic crystallization time (
α
- and
β
). The
temperature dependence of the crystallization time for amorphous SSR (an investiga-
tional compound) showed a correlation with the slope of the
τ
β
a
-relaxation line, inferring
that the crystallization kinetics was coupled with the
β
-relaxation process. Vyazovkin
and Dranca [27] studied the
-relaxation processes for amorphous indomethacin
using DSC and proposed that at temperatures around
T
g
, the crystallization rate was
α
- and
β
