Controlled Dissolution of Griseofulvin Solid Dispersions
from Electrosprayed Enteric Polymer Micromatrix Particles: Physicochemical
Characterization and <i>in Vitro</i> Evaluation
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Abstract
The oral bioavailability
of a poorly water-soluble
drug is often inadequate for the desired therapeutic effect. The bioavailability
can be improved by enhancing the physicochemical properties
of the drug (e.g., dissolution rate, permeation across the gastrointestinal
tract). Other approach include shielding the drug from the gastric
metabolism and targeted drug release to obtain optimal drug absorption.
In this study, a poorly water-soluble model drug, griseofulvin,
was encapsulated as disordered solid dispersions into Eudragit L 100-55
enteric polymer micromatrix particles, which were produced by
electrospraying. Similar micromatrix particles were also
produced with griseofulvin-loaded thermally oxidized mesoporous
silicon (TOPSi) nanoparticles dispersed to the polymer micromatrices.
The <i>in vitro</i> drug dissolution at pH 1.2 and 6.8,
and permeation at pH 7.4 across Caco-2/HT29 cell monolayers from the
micromatrix particles, were investigated. The micromatrix
particles were found to be gastro-resistant, while at pH 6.8 the griseofulvin
was released very rapidly in a fast-dissolving form. Compared to free
griseofulvin, the permeability of encapsulated griseofulvin
across the intestinal cell monolayers was greatly improved, particularly
for the TOPSi-doped micromatrix particles. The griseofulvin
solid dispersions were stable during storage for 6 months at accelerated
conditions. Overall, the method developed here could prove to be a
useful oral drug delivery solution for improving the bioavailability
of poorly water-soluble or otherwise problematic drugs