Chemistry Reference
In-Depth Information
determined by helium displacement pycnometry for the separate pure components. The
changes in thermal expansivity for each pure component can be approximated using the
values of
T
g
for each component [30]. The GT equation only applies to binary mixtures in
which the components are fully miscible over the entire composition range. The
Couchman
Karasz (CK) equation is another popular approach to prediction of
T
g
and is particularly well-suited to cases where the drug acts as a plasticizer upon the
polymer [31]. The
T
g
of a mixture is again predicted using Equation 4.2 but with
K
GT
replaced by
K
CK
[18]:
-
K
CK
Δ
C
p
;
2
C
p
;
1
:
(4.4)
Δ
Here,
c heat capacity for
components 1 and 2 measured at the
T
g
values separately obtained from pure amorphous
components. These values are readily measured if it is possible to prepare pure
amorphous components, although not all drugs are easily prepared as amorphous phases.
Other equations have also been developed to predict glass transitions in binary
amorphous systems, but are not as commonly employed, and at present no universal
equation capable of modeling all systems has been proposed [18].
Both the GT and CK equations predict an increase in
T
g
that is proportional to the
mass fraction of the higher
T
g
component, and an experimental
Δ
C
p
,1
and
Δ
C
p
,2
, respectively, represent the changes in speci
finding of this prediction
is often used to support the proposition that the two components are miscible [18].
Deviations from the GT and CK equations are normally interpreted to mean that a
violation of the assumption of non-interacting components has occurred. For example,
T
g
values obtained by DSC for dispersions of a compound known as MK-0591 with PVP
were higher than those predicted by the Gordon
-
Taylor equation, indicating the presence
of drug
-
polymer interactions [32]. Negative deviations from the Gordon
-
Taylor equa-
tion have also been observed in other DSC studies [18].
Fast-scanning DSC is a more recently developed technique that also has applications
to amorphous solid dispersions [33]. The key bene
t of fast DSC is that the heat is
applied rapidly, so that changes in temperature during the measurement do not have
enough time to affect the miscibility of the drug and the polymer. As a result, fast-
scanning DSC can allow for a better understanding of miscibility in amorphous solid
dispersions. DSC experiments on polymers can also be performed under variable
pressure in different gaseous atmospheres, which affects the heat capacity and measured
T
g
value of an amorphous material, potentially allowing new observations or more
detailed analysis in challenging systems [34].
ITC is a complementary thermal analysis technique that generally requires a larger
amount of sample but can measure much smaller heat
flows [35]. ITC is more commonly
employed in the detection of small amounts of amorphous content in crystalline pharma-
ceuticals [36]. However, applications of ITC to the study of two-phase amorphous systems
such as dispersions have appeared [37]. In particular, ITC can be used to study relaxation
of amorphous solid dispersions, as these amorphous states continually evolve toward
lower energy arrangements. In these studies, ITC can be used to study detect the rate of
heat release during structural relaxation of an amorphous solid, and the relaxation
