Chemistry Reference
In-Depth Information
and
C
G
is a constant given by
C
G
D
exp
H
L
H
m
RT
:
(4.7)
In Equations 4.6 and 4.7,
B
and
D
are constants,
H
L
is the heat of conduction of the bulk
adsorbate, and
H
m
is the heat of adsorption of vapor adsorbed as intermediate bound
water [48]. The GAB equation allows for modeling of the GVS isotherm for amorphous
solid dispersions of interest and quantitative comparisons of these
tted parameters. In
GVS studies of amorphous dispersions, kinetic effects often lead to hysteresis, in that the
increasing and decreasing RH isotherms are not reversible [48,52]. This effect is also
commonly attributed to changes in polymer conformation resulting from the plasticizing
effect of water [52].
A detailed study of the effect of RH on
T
g
for PVP was performed using variable-
temperature GVS and thermal analysis, and is illustrative of the type of characterization
data that can be obtained for dispersion-forming polymers [53]. The amount of water
absorbed at a given RH increased as temperature decreased, with a corresponding change
in the shape of the isotherm. PVP was observed to change from a highly viscous glass to a
much less viscous rubber in the same region where absorbed water behaves as if it is in a
liquid-like mobile state. The appearance of tightly bound water was found to correlate
with the polymer entering the glassy state. GVS instruments also enable a number of
practical applications for amorphous solid dispersions. For example, GVS studies of the
kinetics of the uptake of moisture by dispersions can be useful in predicting the results of
longer term stability studies at elevated RH. Finally, GVS techniques that utilize organic
solvent vapors instead of moisture are also available, and may be useful in the design and
development of organic spray drying processes and subcritical or supercritical
uid
processes for manufacturing amorphous solid dispersions [54].
4.5 VIBRATIONAL SPECTROSCOPY AND MICROSPECTROSCOPY
In the pharmaceutical sciences, vibrational spectroscopic methods are generally used to
probe molecular vibrations and phonon modes in crystalline substances. The principal
techniques used at present are based on infrared (IR) spectroscopy and Raman spec-
troscopy [55]. In IR spectroscopy, the absorption, transmission, or re
ectance of IR
radiation by a sample is measured. The IR spectrum is divided into three regions
according to the wavelength or frequency of the radiation: the near-IR (NIR) region
between 0.78 and 2.5
m (12,800 to 4000 cm
1
), the mid-IR (mid-IR) region between 2.5
μ
m (4000 to 200 cm
1
), and the far-IR region between 50 and 1000
and 50
m (200 to
1cm
1
). All three regions have been employed in studies of amorphous solid disper-
sions. Vibrational bands observed in the mid-IR region typically arise from single-
quantum (
μ
μ
1) vibrational modes, while the NIR region generally measures over-
tone bands with a higher
Δ
ν
=±
value. The far-IR region (200 to 10 cm
1
) generally observes
low-frequency phonon modes (also known as lattice vibrations) in crystalline materials,
which can be useful
Δ
ν
to detect crystallinity in amorphous solids. Amorphous and
