Chemistry Reference
In-Depth Information
limited in some cases by the resolution of the IR spectra and by the inability to prepare
stable physical mixtures of amorphous drugs in polymers for some systems. Studies
using different IR sampling modes have obtained similar results. For example, an ATR
IR spectroscopic study of ibuprofen impregnated into PVP using a supercritical
uid
detected interactions between the drug and the C
O group within PVP [62]. A study of a
dispersion of ketoconazole and PVP utilized IR as well as
13
C SSNMR and DSC to study
interactions between the drug and the polymer [63]. IR spectroscopy was also applied to
study interactions of indomethacin, lacidipine, nifedipine, and tolbutamide in PVP and
polyvinylpyrrolidone-
co
-vinyl acetate (PVP-VA) in dispersions produced by hot melt
extrusion [64].
NIR spectroscopy has also been used in studies of amorphous solid dispersions. The
NIR spectrum of organic substances is typically less speci
c than other regions of the IR
spectrum, and is made up of sum and difference combination bands and
rst, second, and
third overtone bands arising from the fundamental vibrational modes observed in the mid-
IR region. NIR spectroscopy has advantages over mid-IR spectroscopy because of the
weak nature of overtone and combination bands, which allows for studies of powdered
solid samples without saturation [65]. Many IR spectrometers can be con
gured to analyze
both NIR and mid-IR spectra using an appropriate set of sources, detectors, and optical
components (e.g., beam splitters). Applications of NIR spectroscopy have been reported
for studies of amorphous solid dispersions. For example, a combination of NIR spectros-
copy andmultivariate analysis using PLS has been employed as a sensitive, nondestructive
measure of crystalline content in tacrolimus dispersions after calibration of the method
using dispersions spiked with crystalline material [66]. Drug
polymer interactions in an
amorphous solid dispersion of tranilast in the polymethacrylate polymer Eudragit
EPO
with enhanced solubility and improved oral bioavailability were studied using a combina-
tion of NIR and mid-IR spectroscopic methods [67]. NIR spectroscopy has also been
applied to the study of semicrystalline dispersions of cyclosporin A and polyethylene
glycol (PEG) with enhanced dissolution, primarily to estimate the quantity of drug present,
with mid-IR spectroscopy again applied to probe potential interactions between the drug
and the polymer (in this case detecting no such interaction) [68].
Far-field IR microscopy can be used to perform chemical imaging studies of
amorphous solid dispersions, although spatial resolution is limited by diffraction to
about 25
-
ectance microscopy or imaging is used in a similar
manner to assess homogeneity of dispersions, although multivariate methods are
generally a requirement for data analysis [68]. Imaging studies of formulations can
be facilitated using mid-IR analysis with wide-area ATR sampling and focal planar array
(FPA) detectors [70,71]. In this approach, a diamond or ZnSe ATR crystal with
dimensions in the
μ
m [69]. NIR diffuse re
5mm range (several times larger than a conventional ATR crystal
used in IR analysis) is employed with specialized focusing optics to allow the FPA
detector to obtain mid-IR spectra simultaneously from all regions of the sample in good
contact with the ATR
∼
m. This
approach has been applied to image amorphous solid dispersions of small-molecule
drugs in polymers as well as their release from the dispersion [72,73].
The coupling of IR spectroscopy with atomic force microscopy (AFM) has opened
up new possibilities for the microscopic characterization of dispersions with extremely
“
window,
”
usually with spatial resolution in the tens of
μ
