title: Polymeric microcontainers improve oral bioavailability of furosemide.
abstract: Microcontainers with an inner diameter of 223 μm are fabricated using the polymer SU-8, and evaluated in vitro, in situ and in vivo for their application as an advanced oral drug delivery system for the poorly water soluble drug furosemide. An amorphous sodium salt of furosemide (ASSF) is filled into the microcontainers followed by applying a lid using Eudragit L100. It is possible to control the drug release in vitro, and in vitro absorption studies show that the microcontainers are not a hindrance for absorption of ASSF. In situ perfusion studies in rats are performed with ASSF-filled microcontainers coated with Eudragit and compared to a furosemide solution. The absorption rate constant of ASSF confined in microcontainers is found to be significantly different from the solution, and by light microscopy, it is observed that the microcontainers are engulfed by the intestinal mucus. An oral bioavailability study in rats is performed with ASSF confined in microcontainers coated with Eudragit and a control group with ASSF in Eudragit-coated capsules. A relative bioavailability of 220% for the ASSF in microcontainers compared to ASSF in capsules is found. These studies indicate that the microcontainers could serve as a promising oral drug delivery system.
authors.affiliation: Department of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads 345B, 2800 Kongens Lyngby, Denmark. Electronic address: lihan@nanotech.dtu.dk.
authors.forename: Line Hagner
authors.initials: LH
authors.lastname: Nielsen
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Melero
authors.affiliation: Department of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads 345B, 2800 Kongens Lyngby, Denmark.
authors.forename: Stephan Sylvest
authors.initials: SS
authors.lastname: Keller
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen, Denmark.
authors.forename: Jette
authors.initials: J
authors.lastname: Jacobsen
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Valencia, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Garrigues
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen, Denmark; Bioneer:FARMA, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen, Denmark.
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
authors.affiliation: Department of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads 345B, 2800 Kongens Lyngby, Denmark.
authors.forename: Anja
authors.initials: A
authors.lastname: Boisen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004852:Epoxy Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D005665:Furosemide / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D009093:Mucus / Q000378:metabolism; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011109:Polymethacrylic Acids / Q000737:chemistry; D017208:Rats, Wistar
chemical_list: D004852:Epoxy Compounds; D011108:Polymers; D011109:Polymethacrylic Acids; C520895:SU-8 compound; C038300:methylmethacrylate-methacrylic acid copolymer; D005665:Furosemide
keywords: Delivery systems; Furosemide; Intestinal perfusion; Micro devices; Oral bioavailability; Oral delivery