title: Enhanced in vitro permeation of furosemide loaded into thermally carbonized mesoporous silicon (TCPSi) microparticles.
abstract: The combined release and permeation behavior of furosemide loaded into thermally carbonized mesoporous silicon (TCPSi) microparticles was studied in order to evaluate the potential of TCPSi-loading to improve permeation of furosemide, a BCS class IV compound. Permeation was studied across Caco-2 monolayers at pH 5.5, 6.8 and 7.4 from drug solutions and TCPSi particles. TCPSi-loaded furosemide (39% w/w) exhibited improved dissolution from the microparticles with greatly diminished pH dependence. At pH 5.5, where furosemide solubility restricted the amount that could be dissolved in the control solution to less than 30% of the dose contained in the TCPSi particles, the flux of TCPSi-loaded furosemide across Caco-2 monolayers was over fivefold compared to pre-dissolved furosemide. The improved permeation could be confirmed also from dose-corrected (% dose-permeated) results. At pH 6.8 and pH 7.4, where corresponding doses could be used in control solutions, more than fourfold permeability values were obtained with TCPSi-loaded furosemide. Effects on transepithelial electrical resistance (TEER) and mannitol permeability were monitored and suggest that monolayer integrity was not compromised by the drug-loaded TCPSi microparticles. The improved permeation observed from furosemide-loaded TCPSi particles suggests that the high local concentrations provided by the enhanced dissolution properties of TCPSi-loaded furosemide could prove beneficial for absorption.
authors.affiliation: Drug Discovery and Development Technology Center, University of Helsinki, Finland. ann.m.kaukonen@helsinki.fi
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Kaukonen
authors.forename: Leena
authors.initials: L
authors.lastname: Laitinen
authors.forename: Jarno
authors.initials: J
authors.lastname: Salonen
authors.forename: Jaani
authors.initials: J
authors.lastname: Tuura
authors.forename: Teemu
authors.initials: T
authors.lastname: Heikkilä
authors.forename: Tarja
authors.initials: T
authors.lastname: Limnell
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Vesa-Pekka
authors.initials: VP
authors.lastname: Lehto
mesh_terms: D018938:Caco-2 Cells; D005665:Furosemide / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010539:Permeability; D016062:Porosity; D012825:Silicon / Q000008:administration & dosage*; D012995:Solubility
chemical_list: D005665:Furosemide; D012825:Silicon