Chemistry Reference
In-Depth Information
Figure 1.18.
Overlay of modulated DSC, reversing heat
ow, from top to bottom: indomethacin
prepared by melt quench, 70 and 30wt% indomethacin in PVP dispersions and PVP prepared by
flash evaporation (Reproduced with permission from Ref. 35. Copyright 2008, Wiley-Liss, Inc).
would produce a DSC thermal response that indicates only one
T
Tgmix.
. To further establish
whether amorphous mixtures truly exist in a single phase, it is possible to use PXRD
measurements, as well as SSNMR spectroscopy, since both techniques probe molecular
interactions at a very local level. For example, in the case of PXRD, one can compare
diffraction patterns of the amorphous mixture with those of the individual components, and
if the sum of the weighted average of the patterns of the individual components is the same
as that of themixture, the system is completely phase separated [35]. If the calculated values
for the mixture do not coincide with those experimentally determined, the system can be
considered to exist as a single phase. One also can determine the PDF of the individual
components and the mixture, and similarly compare the sum of the weighted average
of the PDFs of the components with that of the mixture. Again, if the weighted average of
the PDFs of the individual components is the same as that of the mixture, the system is
immiscible, whereas differences indicate miscibility [35]. It is also possible to use solid-
state NMR to detect phase separation down to domain sizes less than 100 nm using two-
dimensional NMR [36] and by measuring
T
1
and
T
1
β
relaxation times that respond to NN
and NNN distance interactions between components. For example, it was recently shown
that a lyophilized amorphous mixture of trehalose and dextran produced a single
T
g
that
changed with the concentration of the components. However, PDF analysis of these
mixtures, as described above, revealed complete phase separation [35]. SSNMRanalysis of
this system revealed, indeed, that separate molecular clusters with dimensions on the order
of 55
-
80 nm could be detected [37].
