Chemistry Reference
In-Depth Information
liquid state and tend to have more complex structures. Thus, it would be expected that a
system with a high
S
conf
would have more conformations to sample before
finding the
“
conformation for nucleation, thus decreasing the nucleation rate and subsequent
crystallization tendency [18]. On a somewhat related topic, similarities or differences in
hydrogen bonding interactions in the amorphous and crystalline states may also in
right
”
uence
the ability of the molecules to nucleate. Similar hydrogen bonding patterns and strengths
in the glass and crystal may lead to more facile crystallization relative to instances where
the strength and/or donor and acceptor group pairings show differences between the two
phases [19]. Miyazaki et al. [20] found that for a series of structurally related
dihydropyridines, the compounds with lower structural symmetry and bulkier side
groups (nitrendipine and nilvadipine) exhibited lower crystallization rates compared
with nifedipine and
m
-nifedipine, further supporting the important role of molecular
structure.
In another study of the crystallization tendency of amorphous dihydropyridines [21],
a higher crystallization tendency (higher nucleation rate) was observed for nifedipine
relative to felodipine. This was correlated with the increase in thermodynamic driving
force for crystallization,
G
conf
. In this instance,
H
conf
was the factor correlating with the
crystallization tendency of these two compounds, not
S
conf
as observed in other studies.
Another study evaluated the effect of heat of fusion (
H
m
) and entropy on the
crystallization tendencies of a series of hexitols (iditol, mannitol, sorbitol, and dulci-
tol) [22]. Here, the experimental observations suggested that the high crystallization
tendencies of mannitol and dulcitol were due to their high
Δ
H
m
and thus higher
thermodynamic driving force for crystallization. Baird et al. [23] studied the crystalliza-
tion tendency of a group of 50 compounds on cooling from the melt and found that, in
general, rapidly crystallizing compounds had lower molecular weights (MWs) and a
larger free energy difference between the crystal and the melt (on a per volume basis)
than more slowly crystallizing compounds.
The interfacial energy is another important thermodynamic factor that will in
Δ
uence
the crystallization tendency, although it is dif
cult to access experimentally. Carpentier
et al. [24] measured the interfacial energies of a series of pentitols in an effort to delineate
the relative contributions of both kinetic and thermodynamic driving forces to observed
crystallization tendencies. The authors found that the crystallization tendencies observed
did not correlate with the change in either the free energy or the molecular mobility of the
compounds. For example, amorphous
L
-arabitol, which had the highest driving force for
crystallization, did not recrystallize on heating, whereas adonitol, with the lowest driving
force, crystallized upon heating. The differences in the crystallization tendencies were
explained based on differences in the speci
c molecular conformations that led to
different liquid
-
crystal interfacial energies.
5.3.2 Molecular Mobility
Crystallization from the amorphous state will be strongly affected by molecular
motions [18]. Molecular mobility includes bending, rotation, and translation of mole-
cules. Generally, crystallization rates will increase if the molecular mobility is increased,
all other factors being equal. However, it is important to consider that supercooled liquids
