5 research outputs found
Where Is the Drug? Quantitative 3D Distribution Analyses of Confined Drug-Loaded Polymer Matrices
To enhance oral bioavailability
of poorly soluble drugs, microfabricated
devices can be utilized. One example of such devices is microcontainers.
These are cylindrical in shape with an inner cavity for drug loading
and with only the top side open for release. Supercritical CO2 (scCO2) impregnation is an interesting technique
for loading drugs into polymeric matrices in, for example, microcontainers
since it avoids the use of organic solvents and is cheap. One of the
main drawbacks of this technique is the unknown three-dimensional
drug distribution in the polymer matrix. The aim of this study was
to investigate the loading of two poorly soluble drugs, naproxen and
ketoprofen, by scCO2 impregnation into confined polymer
matrices of different sizes. Three different sizes of microcontainers
(small, medium, and large) and, thereby, different surface areas accessible
for impregnation were compared. From in vitro studies,
the amount of naproxen and ketoprofen loaded into the different microcontainers
and their corresponding release profiles were seen to be similar.
A custom-made Raman microscope facilitated volumetric Raman maps of
an entire microcontainer filled with polyvinylpyrrolidone (PVP) and
scCO2 impregnated with either naproxen or ketoprofen. In
all microcontainer sizes, the drugs were only detected in the top
layer of the polymer matrix, explaining the observed similar release
profiles. Using X-ray powder diffraction and Raman spectroscopy, the
solid state form of the drugs was evaluated, showing that ketoprofen
was amorphous in all microcontainer sizes. Naproxen was found not
to be crystalline nor amorphous but in a less ordered configuration
than the crystalline state. In conclusion, volumetric Raman mapping
is a powerful technology for imaging drug distribution and drug crystallinity
in polymers and allowed us to conclude that (i) scCO2 impregnation
depth does not depend on surface area and (ii) impregnated drugs are
noncrystalline