posted on 2024-01-19, 09:29authored byNathan
W. Fenwick, Richard Telford, Richard D. Bowen, Colin C. Seaton
The creation of long-lived
amorphous phases has potential applications
in numerous fields; for example, the instability of the amorphous
phase leads to higher solubility of pharmaceutical phases, often leading
to higher bioavailability. The rate of recrystallization of an amorphous
phase poses a significant limitation to the application of many such
phases; however, understanding the energetic and structural factors
that control the stability of molecular amorphous phases is limited
by empirical classifications based on thermal analysis used to identify
materials. From a set of molecularly related benzanilides, examples
of all three classes have been identified, allowing use of crystal
structural analysis, Raman spectroscopy, and energetic calculations
to determine the structural factors playing a role in the different
stabilities. While the behavior of most systems reflects the relative
energy of the crystalline phase to the amorphous phase, kinetic factors
based on whether a NH···OC hydrogen bond is
present in the crystalline phase play a key role in stabilizing the
amorphous phase as the loss of this bond reduces the conversion rate.
In contrast, systems without this bond display fast recrystallization
due to the greater structural similarity between the amorphous and
crystalline phases.