Chemistry Reference
In-Depth Information
mechanism when crospovidone particles were suspended in predissolved griseofulvin
solutions [164]. XPS was found to be useful for imaging the distribution and homoge-
neity of griseofulvin loaded into particles of crospovidone with different morphology
and also con
rmed a diffusion mechanism for the loading process. More recently, XPS
been applied in investigations of solvent interactions with amorphous solid dispersions
of several drugs in HPMC and PVP to investigate a possible correlation between contact
angle measurements, XPS results, and the results of other measurements including
magnetic resonance imaging (MRI) techniques [165,166]. XPS instruments are available
in an increasing number of laboratories, and with decreasing cost and technical advances
in X-ray source designs and detectors, increased application of XPS in pharmaceutical
applications is likely to occur.
A novel method based on second-harmonic generation (SHG) in intense light
elds
has been demonstrated as a more sensitive probe of crystal formation in amorphous
materials than conventional optical microscopic techniques [167]. Themethod is known as
second-order nonlinear optical imaging of chiral crystals (SONICC). In SHG, multiple
photons are absorbed froman intense beamand are converted by a crystal into photons with
twice the frequency [168]. In the initial study, SONICC was sensitive to the detection
of small amounts of recrystallization from amorphous griseofulvin, and should have
similarly sensitive applications to amorphous solid dispersions as the technique is further
developed [167].
4.10 OTHER EMERGING ANALYTICAL METHODS
Rapid developments have occurred in the
field of analytical chemistry, particularly in
areas such as scanning probe microscopy, novel forms of spectroscopy making use of
high-intensity radiation (such as to enable observation of nonlinear phenomena), and
methods that utilize different radiation and particle sources. Some of these methods
have already been demonstrated in initial applications to amorphous solid dispersions.
For example, a study using nanoindentation was performed on dispersion
films of
clotrimazole in PVP
VA to allow for direct measurements of the mechanical propert-
ies of the solid, which are important in amorphous solid dispersion manufacturing
because they can affect downstream processes such as particle size reduction (e.g., via
milling),
-
filling into capsules, and/or compression into tablets [169]. The dispersions
were prepared as
films with drug loading ranging from 0 to 100% (w/w). Interestingly,
the addition of clotrimazole to the polymer reduced the glass transition temperature as
observed by DSC, but the hardness, reduced elastic modulus, and storage modulus as
measured by nanoindentation were found to increase to values greater than those of
either pure component up to drug loadings of approximately 60% (w/w). Above this
point, addition of clotrimazole to the system resulted in decreased hardness and
moduli. This suggests a complex interplay between structural composition and
properties that can be of signi
cance in choosing the best formulation for manufactur-
ing. Nanoindentation is also increasingly applied in studies of crystalline materials,
again to measure elastic modulus and the onset of plastic deformation on cleaved
surfaces, and may be useful
in studies where amorphous solid dispersions are
