Chemistry Reference
In-Depth Information
Figure 5.3.
Nucleation rate of amorphous
felodipine at 25
°
C following storage at
different relative humidities illustrating the
rapid increase in nucleation rate as the
storage relative humidity is increased.
The increased molecular mobility that results following water sorption will increase the
crystallization tendency of an amorphous material. Andronis et al. [45] showed that
increasing the storage relative humidity for amorphous indomethacin increased the
amount of moisture sorbed by the system, resulting in a decrease in the measured
T
g
and
increased crystallization rate. Another study reported the impact of moisture sorption on
the crystallization of amorphous lamotrigine mesylate [46]. Increasing the amount of
moisture sorbed in the system decreased the glass transition of the material and onset
temperature for crystallization; hence, increasing the amount of water present increased
the crystallization tendency from the amorphous state. Quantitative studies of crystal
nucleation rates [47] and crystal growth rates [48] of felodipine exposed to different RH
conditions illustrate the large impact of absorbed moisture on crystallization. Figure 5.3
shows the measured nucleation rate for the hydrophobic compound felodipine as a
function of storage RH. Dry felodipine has a
T
g
of around 43
°
C, and this decreases to
about 35
C reduction in
T
g
, the
nucleation rate increases by more than an order of magnitude, illustrating the extremely
potent impact of absorbed moisture on crystallization behavior.
C following storage at 75% RH [47]. For this 10
°
°
5.3.3 Impact of Preparation Method and Processing Steps
It is well recognized that the properties of amorphous materials are highly dependent on
both thermal and processing history. Common routes of preparing amorphous materials
include rapid cooling from the melt, condensation from the vapor state, mechanical
disruption of the crystalline lattice, and precipitation from solution and drying. Each of
these different methods will yield a glass with different thermodynamic properties,
whereby the various glasses have undergone different extents of structural relaxation.
For example, the preparation method has been found to in
uence the enthalpic relaxation,
crystallization tendency, and water vapor sorption of amorphous trehalose [49]. Based on
isothermal crystallization studies, it was observed that the dehydrated material crystallized
fastest, followed in order by the freeze-dried, spray-dried, and melt-quenched material. In
addition to in
uencing the thermodynamic properties of the glass, the preparation method
