Chemistry Reference
In-Depth Information
Figure 1.22.
Glass transition
temperature of amorphous
indomethacinas a functionofwater
content (reproduced with
permission from Ref. 52. Copyright
1997, John Wiley & Sons, Inc.).
about 1% w/w at 50% RH and 2% w/w at 83% RH, whereas water vapor absorption
at room temperature by PVP, HPMC, and HPMCAS at 75% RH is about 26% w/w,
10% w/w, and 7% w/w, respectively. These results are consistent with the general order
of polarity and hydrogen bonding ability of these polymers. What they also indicate is
that most of the water that is absorbed by a typical API
polymer dispersion would be
expected to be associated with the polymer. This is a reasonable generalization since
amorphous dispersions are prepared because the API is usually somewhat hydrophobic.
Water absorbed into an amorphous solid would be expected to have an effect on the bulk
properties of the solid, for example,
T
g
and molecular mobility, as can be seen in
Figure 1.22, where
T
g
is plotted versus water content for amorphous indomethacin. Here,
we can see that in both cases water acts to reduce
T
g
very signi
-
cantly, acting as an
excellent plasticizer. Such plasticizing effects can be roughly predicted for any water
content by applying Equation 1.32 and using the values of 136, 315, and 453 K for the
T
g
of water,
indomethacin, and PVP, respectively. Consider,
first, a situation where
indomethacin alone is exposed to an environment at 40
C and 75% RH, resulting in
a concentration of water in the API of about 1.7% w/w. From the application of
Equation 1.32, it can be shown that
T
g
would be reduced from 315 to about 308 K,
whereas storage of PVP at 40
°
C and 75% RH, with 26% w/w water being absorbed,
leads to a reduction of the
T
g
of PVP from 453 to 282 K. Such a signi
°
cant reduction in
T
g
close to 0
C where the sample
is stored at 31 K above the new
T
g
of PVP in the supercooled liquid state. One might
mitigate this result to some extent by choosing to use a less polar polymer such as HPMC
that has a dry
T
g
of about 175
C (273 K) would clearly create signi
cant mobility at 40
°
°
C (448 K) and absorbs 10% w/w water at 75% RH. From
Equation 1.31 we can calculate that the
T
g
of HPMC in the presence of 10% w/w water
would be reduced to 364 K, and therefore when stored at 40
°
C it would be 52 K below
T
g
in the glassy state, a much better solution for preventing crystallization in the hydrated
°
