Chemistry Reference
In-Depth Information
tenoxicam [25]. Spectra measured byDRUV
visible spectroscopy can be reduced to color
coordinates for assessment of the appearance of a batch using a set of values designed to
correlate to human color perception [144]. Several different color coordinate systems are in
use, including systems designed to be sensitive to the pale and off-white colors frequently
encountered with pharmaceutical amorphous solid dispersions, allowing for straight-
forward quantitative appearance testing for quality control [144,145].
Fluorescence spectroscopy detects emitted
-
fluorescence upon excitation using
UV
visible radiation, and can be performed in several modes including emission scans
with a constant excitation wavelength, excitation scans with a constant emission wave-
length, synchronous scans of both monochromators, and total luminescence scans [146].
Solid-state fluorescence spectroscopy has potential in the study of amorphous solid
dispersions, although only limited pharmaceutical applications have appeared to date
primarily in studies of crystalline systems that undergo solvation phenomena [147].
Sampling of solid-state materials is typically accomplished using a front-facing sample
holder offset at a slight angle (15
-
-
30
) relative to the excitation beam and re
ected to the
°
detector using a separate optical path than used for the normal 90
observation in solution-
°
state
fluorescence spectroscopy. The holder contains a small amount of packed solid
material behind a quartz plate or similarly
fluorescence-free, transparent material.
fluorescence spectroscopy offers great sensitivity for applications in
amorphous dispersions, but can suffer from limited speci
Solid-state
city. In Figure 4.14a, the solid-
state
fluorescence emission spectra of amorphous dispersions of 30% (w/w) di
unisal in
two polymers are shown [79]. Signi
cant differences in intensity and emission maxima
are observed between crystalline Form I and the dispersions in PVP and HPMCAS. The
differences between the
fluorescence spectra of the two dispersions are likely related to
differences in the mobility of di
unisal in the glassy solid [147]. The overall lack of
speci
city limits the use of this technique for analysis of residual Form I content in either
of the dispersions, however. This is not the case with the example shown in Figure 4.14b,
where the
fluorescence spectra of three dispersions of 1:2 tenoxicam:
L
-arginine in PVP
are compared with the spectrum of crystalline Form III, because the latter exhibits much
greater intensity and an emission maximum shift that would be useful for detection of
residual Form III [25]. These dispersions were previously studied by DR UV
-
visible
spectroscopy, as noted above. In Figure 4.14b, the solid-state
fluorescence spectrum of
Form III is seen to be distinctive relative to the spectra of the dispersions, with a Stokes-
shifted emission maximum and a signi
cant increase in intensity that is likely attributable
to the zwitterionic state of tenoxicam in Form III [25]. The spectra of the dispersions
show a more subtle shift in emission maximum compared with each other, as expected
given the monoionic state of the drug, and also highlight the quantitative nature of
fluorescence intensity versus drug concentration.
◀
d
6
-DMSO. Spectrawere obtained at
ν
r
= 8 kHz. A signi
cant signal enhancement is again observed
in the spectrum obtained with microwaves on. All spectra in (a) and (b) were obtained using a
Bruker Avance III wide bore spectrometer operating at 9.4 T with a 263GHz gyrotron and
microwave transmission line, using a 3.2mmMAS probe with sapphire rotors at a temperature of
approximately 100K. Other details of the system are described elsewhere [142].
