Chemistry Reference
In-Depth Information
typical dispersion to be completed after several hours using these experiments [105]. The
CP process provides a signi
cant enhancement of
13
C spectral signal relative to single-
pulse direct polarization MAS (DP-MAS) experiments [106].
13
C spectra of dispersions
often contain many resonances, and the potential for overlap with MAS sidebands is
high. Because these can complicate interpretation, a common approach is to remove the
sidebands experimentally using TOSS pulse sequences [107]. Finally, the performance
of the decoupling of
1
H nuclei is critical to the quality of
13
C spectra, and decoupling
pulse sequences such as SPINAL-64 are commonly performed at RF powers of
approximately 100 kHz to ensure good results on dispersions [108].
Several types of information can be obtained from a 1D
13
C SSNMR spectrum. First,
the resonances are expected to be broad because the amorphous nature of thematerial leads
to a range of
13
C sites with different chemical shielding environments. The observation
of sharp resonances is normally an indication of crystalline content. In Figure 4.7, 1D
13
C
20% drug in HPMCAS
HPMCAS
HPMCAS
HPMCAS
HPMCAS
HPMCAS
PVP
PVP
PVP
20% drug in PVP
PVP
HPC
20% drug in HPC
HPC
HPC
HPC
HPC
Crystalline drug
190 180 170 160 150 140 130 120 110 100 90
80
70
60
50
40
30
20
10
13
C chemical shift (ppm from TMS)
Figure 4.7.
13
C CP-TOSS spectra of 20% (w/w) dispersions of the drug 6-(2-(5-chloro-2-(2,4-
di
uorobenyzloxy)phenyl)cyclopent-1-enyl)picolinic acid in HPMCAS, HPC, and PVP prepared by
acetone/methanol solvent evaporation [86]. The
13
C CP-TOSS spectrum of a crystalline form of
this compound is shown for comparison. The
13
C resonances assigned to polymer sites are noted
on each spectrum, and the spectra show the generally resolved nature of polymer resonances
relative to resonances of a typical pharmaceutical compound that is obtained using this
characterization technique.
