Chemistry Reference
In-Depth Information
disordered solids generally exhibit broader bands in this region because of their lack of
long-range order, and may not exhibit any bands at all [56].
A number of sampling modes are available for IR spectroscopic analysis of bulk
substances [55]. One of the most popular is attenuated total re
ectance (ATR) sampling,
which consists of contacting a solid sample surface with a material with a different
refractive index and re
ecting the IR beam from the interface [55]. An evanescent wave
forms and travels along the surface region, which leads to IR absorbance that can be
detected in the re
ected IR radiation. ATR sampling is a simple and robust method,
particularly for routine analysis, but yields reduced absorbance at higher frequencies
(corresponding to higher wavenumbers) and can lead to dif
culty in observation of
stretching vibrations of interest in hydrogen bonding studies such as those involving
O
-
H and N
-
H groups. Transmission IR spectroscopy using KBr or CsI pellets or thin
films of solvent-evaporated dispersions on NaCl plates is also used to analyze solid
materials [55]. These methods do not suffer from the ATR signal attenuation issue at
higher wavenumbers. However, the preparation of the pellet necessarily involves mixing
the sample with the salt and applying pressure to achieve cold
flow, which can cause
changes to the sample including changes in water and solvent content. Diffuse re
ec-
tance IR measurements (commonly referred to as DRIFTS) can be used directly on
powders with minimal sample preparation in cases where neither ATR nor transmission
methods are applicable, albeit with a loss of sensitivity [55]. DRIFTS can typically be
performed on neat samples with modern accessories, but dilution in materials such as
KBr and CsI may be necessary in some cases if bands of interest are saturated, again with
the potential for undesirable effects on the water content of the sample. Transmission IR
and DRIFTS methods also generally expose the sample to dry N
2
purge gas (unlike ATR
sampling), again with potential unwanted effects.
IR spectroscopy can be used to identify drug
c interactions in
amorphous solid dispersions through changes in peak shape or position that are related
to molecular interactions. In particular, mid-IR spectroscopy is a useful probe of
hydrogen bonding for speci
-
polymer-speci
c functional groups particularly through analysis of the
vibrational frequencies of O
H, and C
O bonds [57,58]. For example, the
stretching frequencies of O-H and N-H groups acting as hydrogen bond donors tend to
decrease and their bands tend to broaden as hydrogen bond donor
-
H, N
-
acceptor distances get
shorter [57,58]. The detection of hydrogen bonding between the drug and polymer can be
important because such an interaction can inhibit crystallization in an amorphous solid
dispersion. For example, in a study of indomethacin in PVP, the inhibition of crystalli-
zation was linked to the observation by mid-IR spectroscopy of drug
-
polymer hydrogen
bonds, which prevented formation of a competing dimeric interaction between indo-
methacin molecules that stabilized the crystalline form [59]. In this study, a range of
indomethacin dispersions in PVP were probed with IR spectroscopy using transmission
sampling in KBr pellets [60]. The spectra of the dispersions were compared to identify
interactions between the drug and the polymer. Model solution-phase systems of
indomethacin, methylpyrrolidone, and acetic acid were used to help qualitatively
interpret the IR spectra to understand the carbonyl band frequencies arising from free
pyrrolidone, hydrogen-bonded dimers of carboxylic acids, and carboxylic acids engaged
in hydrogen bonding to pyrrolidone carbonyl acceptors. In Figure 4.2, expanded regions
-
