title: Controlled Dissolution of Griseofulvin Solid Dispersions from Electrosprayed Enteric Polymer Micromatrix Particles: Physicochemical Characterization and in Vitro Evaluation.
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 in vitro 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.
authors.affiliation: †Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Roine
authors.affiliation: †Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland.
authors.forename: Martti
authors.initials: M
authors.lastname: Kaasalainen
authors.affiliation: ‡Laboratory of Electron Microscopy, University of Turku, FI-20014 Turku, Finland.
authors.forename: Markus
authors.initials: M
authors.lastname: Peurla
authors.affiliation: §Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Correia
authors.affiliation: §Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.|∥INEB-Instituto de Engenharia Biomédica, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.|⊥ICBAS-Instituto Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, 4050-313 Porto, Portugal.
authors.forename: Francisca
authors.initials: F
authors.lastname: Araújo
authors.affiliation: §Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
authors.affiliation: †Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Murtomaa
authors.affiliation: †Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland.
authors.forename: Jarno
authors.initials: J
authors.lastname: Salonen
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D001682:Biological Availability; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D006118:Griseofulvin / Q000737:chemistry* / Q000493:pharmacokinetics; D019073:HT29 Cells; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry; D010539:Permeability; D011108:Polymers / Q000737:chemistry*; D012825:Silicon / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; C446821:Eudragit L100-55; D011108:Polymers; D014867:Water; D006118:Griseofulvin; D012825:Silicon
keywords: drug dissolution; drug permeability; electrospraying; enteric release; improved bioavailability; porous silicon; solid dispersion