title: pH-triggered drug release from biodegradable microwells for oral drug delivery.
abstract: Microwells fabricated from poly-L-lactic acid (PLLA) were evaluated for their application as an oral drug delivery system using the amorphous sodium salt of furosemide (ASSF) as a model drug. Hot embossing of PLLA resulted in fabrication of microwells with an inner diameter of 240 μm and a height of 100 μm. The microwells were filled with ASSF using a modified screen printing technique, followed by coating of the microwell cavities with a gastro-resistant lid of Eudragit® L100. The release behavior of ASSF from the coated microwells was investigated using a μ-Diss profiler and a UV imaging system, and under conditions simulating the changing environment of the gastrointestinal tract. Biorelevant gastric medium (pH 1.6) was employed, after which a change to biorelevant intestinal release medium (pH 6.5) was carried out. Both μ-Diss profiler and UV imaging release experiments showed that sealing of microwell cavities with an Eudragit® layer prevented drug release in biorelevant gastric medium. An immediate release of the ASSF from coated microwells was observed in the intestinal medium. This pH-triggered release behavior demonstrates the future potential of PLLA microwells as a site-specific oral drug delivery system.
authors.affiliation: Department of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads, Building 345B, Kongens Lyngby, Denmark, lihan@nanotech.dtu.dk.
authors.forename: Line Hagner
authors.initials: LH
authors.lastname: Nielsen
authors.forename: Johan
authors.initials: J
authors.lastname: Nagstrup
authors.forename: Sarah
authors.initials: S
authors.lastname: Gordon
authors.forename: Stephan Sylvest
authors.initials: SS
authors.lastname: Keller
authors.forename: Jesper
authors.initials: J
authors.lastname: Østergaard
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
authors.forename: Anja
authors.initials: A
authors.lastname: Boisen
mesh_terms: D020341:Absorbable Implants; D000284:Administration, Oral; D002214:Capsules; D004058:Diffusion; D004343:Drug Implants / Q000008:administration & dosage / Q000138:chemical synthesis*; D005665:Furosemide / Q000008:administration & dosage / Q000737:chemistry*; D005750:Gastric Juice / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry*; D008422:Materials Testing; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*
chemical_list: D002214:Capsules; D004343:Drug Implants; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D005665:Furosemide