Chemistry Reference
In-Depth Information
crystallization kinetics of felodipine solid dispersions prepared at different weight ratios
with either PVP or HPMCAS were evaluated as a function of RH storage conditions. It
was found that the PVP dispersions were very stable when stored at low RH conditions,
but rapidly crystallized when stored above 75% RH, 25
C. In contrast, the HPMCAS
dispersions were much more robust to the effects of absorbed moisture, and showed
fairly similar crystallization kinetics regardless of the storage conditions [102]. Trace
crystallinity in tacrolimus amorphous dispersions was evaluated with a variety of
techniques including XRPD [97]. For this system, near-infrared spectroscopy was found
to be a superior technique to XRPD. Amorphous solid dispersions of resveratrol
formulated with different polymers were subjected to a variety of harsh storage
conditions including elevated temperatures and high RH, in order to compare the ability
of different polymers to prevent crystallization [103]. The evolution of crystallinity in the
samples was followed using XRPD. It was found that PVP and Eudragit E100 formed the
most stable dispersions with resveratrol and these systems were remarkably stable to
crystallization, remaining amorphous for several months. In another study, crystallinity
in several drug polymer blends immediately following melt extrusion was evaluated
using a combination of XRPD and DSC [104]. For some samples, diffraction peaks were
observed with XRPD and a melt endotherm was present in the DSC thermogram. The
presence of crystalline material for the samples was thought to arise from incomplete
melting of the drug during the extrusion process.
°
5.5.3 Solid-State Nuclear Magnetic Resonance Spectroscopy
Solid-state nuclear magnetic resonance spectroscopy (SSNMR) has been used to
investigate a number of aspects of amorphous solid dispersions, including miscibil-
ity [105,106], molecular mobility [107], intermolecular interactions [108], and ionization
state [109], and for the detection [106] and quantitation of crystallinity [110] in
dispersions.
SSNMR has been applied in a number of studies to evaluate mobility in single-
component and multicomponent amorphous systems [16,107,111
19
F SSNMR,
-
114].
which can be used if the drug or polymer contains one or more
fluorine atoms, was used
to compare and contrast the mobility of
flufenamic solid dispersions prepared either with
PVP or hydroxypropylmethyl cellulose (HPMC) at a 20% drug loading. The crystalli-
zation kinetics were also evaluated using NMR spectroscopy and correlated with
differences in the observed molecular mobility. By measuring parameters relating to
the rotational molecular mobility,
it was observed that
the molecular mobility of
flufenamic acid was higher in a HPMC dispersion relative to the PVP dispersion.
The stability of
flufenamic acid to crystallization was found to be better in the PVP
dispersion compared with the HPMC dispersion, and this was attributed to the lower
molecular mobility in the former dispersion.
One advantage of SSNMR spectroscopy is the ability to extract information about
the local environment of the drug, which can enable miscibility to be determined at
different length scales [105,106]. Thus, by measuring different relaxation times, some
estimate of the length scales of drug and polymer domains can be achieved, based on the
assumption that the relaxation time of the solid dispersion will be monoexponential but
