Controlled Dissolution of Griseofulvin Solid Dispersions from Electrosprayed Enteric Polymer Micromatrix Particles: Physicochemical Characterization and <i>in Vitro</i> Evaluation

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