Chemistry Reference
In-Depth Information
relaxation measurements can also be useful in studies of phase heterogeneity and probe
shorter range
1
H spin diffusion effects that occur during a
1
H spin-lock pulse [106]. A
recent study observed both uniform
1
H
T
1
and
1
H
T
1
ρ
relaxation times using
13
C
detection for a series of amorphous solid dispersions between peaks assigned to the drug
and peaks assigned to the polymer and other components, which was consistent with the
molecular-scale mixing of the components observed by 2D SSNMR and DSC [25]. If a
statistically signi
cant difference in
1
H
T
1
or
1
H
T
1
ρ
is obtained between
13
C resonances
(or another heteronucleus) assigned to the polymer and those assigned to the drug, then
the system is likely to be heterogeneous with respect to amorphous phases, which could
result from an immiscible system, from the presence of a mixture of amorphous domains
containing different drug/polymer ratios, or from a mesoporous dispersion that is
fundamentally heterogeneous [122]. A uniform
1
H
T
1
or
1
H
T
1
ρ
relaxation time is
expected for a homogeneous phase because of strong
1
H spin diffusion effects at lower
MAS rates, which equalize relaxation processes over longer timescales typically on the
order of at least several milliseconds [136]. However, detection of a uniform
1
H
T
1
or
1
H
T
1
ρ
relaxation time for a material does not provide the same level of proof of phase
association as the 2D SSNMR experiments described above because of the possibility of
degenerate (i.e., statistically indistinguishable) relaxation times between the phases. In
the use of
1
H
T
1
or
1
H
T
1
ρ
relaxation measurements on amorphous solid dispersions, it is
important to note that the polymers in many dispersions have some permeability to
paramagnetic O
2
gas and can be purged over time using the N
2
gas often used for
spinning; as a result, it may be necessary to spin a rotor for a period of time to obtain
consistent
1
H
T
1
results (or otherwise purge the material of O
2
gas), or alternatively spin
the sample using air as a bearing and drive gas instead of N
2
. The use of
1
H
T
1
or
1
H
T
1
ρ
relaxation time analysis for phase disassociation studies should be distinguished from
their use to study mobility, which is discussed next.
Another major class of SSNMR experiments includes those useful for studying
molecular mobility in solids. Information about molecular mobility over a wide range of
timescales can be obtained using SSNMR methods. The nuclei accessed in SSNMR
experiments undergo a variety of relaxation processes that can potentially report on
mobility. SSNMR analysis of mobility in amorphous solid dispersions is therefore
complementary to thermal analysis and dielectric spectroscopy techniques. Lineshape
modeling can provide some information about speci
c dynamic motional models in solids,
but in the typical case of an amorphous solid dispersion, the overall mobility of the solid is
of interest. SSNMR relaxation methods are widely used to assess overall mobility in
amorphous materials including dispersions, typically through measurements of
13
Cor
19
F
T
1
relaxation times [122,137,138]. Mobility in an amorphous phase measured by SSNMR
relaxation time analysis can be related to the tendency to crystallize in some cases [137].
Measurements of
1
H
T
1
ρ
relaxation times provide a convenient measure of overall
molecular mobility in the kHz amplitude regime in an amorphous solid dispersion, and thus
are sensitive to the mobility increase that follows a glass transition. A study of amorphous
solid dispersions containing 50% (w/w) nifedipine in PVP (exhibiting a single
T
g
with an
onset at 67.1
C by DSC) and 50% (w/w) indomethacin in PVP (exhibiting a single
T
g
with
an onset at 71.6
°
C by DSC) was made using variable-temperature
1
H
T
1
ρ
measurements to
illustrate the ability of this approach to detect increases inmotion below the
T
g
measured by
°
