Chemistry Reference
In-Depth Information
CP-MAS
CP-MAS with filter
Crystalline reference
-52
-54
-56
-58
-60
-62
-64
-66
-68
-70
-72
-74
19
F chemical shift (ppm from CFCl
3
)
Figure 4.8.
Detection of crystalline content by
19
F CP-MAS in a dispersion of a
fluorinated drug
containing a small amount of crystalline material introduced by physical blending. The top
spectrum shows the centerband region of a conventional CP-MAS spectrum of the dispersion,
while the middle spectrum shows a CP-MAS spectrum obtained using a 40ms spin lock prior to
the CP transfer on the
1
H channel, which enhances the signal from the crystalline fraction. The
bottom spectrum shows a reference spectrum of the crystalline phase. Spectra were obtained
at 11.7 T and 273K.
of orbital overlap [95,125]. 2D SSNMR techniques are particularly valuable in studies of
amorphous solid dispersions because they allow for direct, unambiguous detection of
interactions between the drug and polymer as well as observation of structural effects such
as hydrogen bonding, ionization state (for ionizable drugs, polymers, or additives), and
molecular conformation [25,79,119,121,122]. Several 2D SSNMR pulse sequences that
are particularly useful in the analysis of amorphous solid dispersions are summarized in
Table 4.1. The experiments that allow for direct detection of drug
polymer interactions are
generally based on through-space dipolar coupling interactions. Direct dipolar interactions
between nuclei of interest in dispersions are typically limited to the 3
-
5Å range because of
the
r
3
dependence of the dipolar coupling (where
r
is the internuclear distance) [95,96].
The heteronuclear correlation (HETCOR) class of pulse sequences are particularly useful
because they correlate a heteronucleus, such as
13
C,
19
F,
23
Na, or
31
P, with
1
H nuclei
directly through space or through a longer range process known as spin diffusion (see
below) [119,126,127]. The use of
1
H nuclei in one of the spectral dimensions confers
suf
-
cient sensitivity on the experiment for it to be of practical use, while the use of a
heteronucleus in the other spectral dimension enhances the speci
city. In the study of
dispersions, this increases the likelihood that, for example, a
1
H (or
13
C) resonance that can
