title: Optimization of the Ussing chamber setup with excised rat intestinal segments for dissolution/permeation experiments of poorly soluble drugs.
abstract: BACKGROUND
  Prediction of the in vivo absorption of poorly soluble drugs may require simultaneous dissolution/permeation experiments. In vivo predictive media have been modified for permeation experiments with Caco-2 cells, but not for excised rat intestinal segments.
  
  
  OBJECTIVE
  The present study aimed at improving the setup of dissolution/permeation experiments with excised rat intestinal segments by assessing suitable donor and receiver media.
  
  
  METHODS
  The regional compatibility of rat intestine in Ussing chambers with modified Fasted and Fed State Simulated Intestinal Fluids (Fa/FeSSIFmod) as donor media was evaluated via several parameters that reflect the viability of the excised intestinal segments. Receiver media that establish sink conditions were investigated for their foaming potential and toxicity. Dissolution/permeation experiments with the optimized conditions were then tested for two particle sizes of the BCS class II drug aprepitant.
  
  
  RESULTS
  Fa/FeSSIFmodwere toxic for excised rat ileal sheets but not duodenal sheets, the compatibility with jejunal segments depended on the bile salt concentration. A non-foaming receiver medium containing bovine serum albumin (BSA) and Antifoam B was nontoxic. With these conditions, the permeation of nanosized aprepitant was higher than of the unmilled drug formulations.
  
  
  CONCLUSIONS
  The compatibility of Fa/FeSSIFmoddepends on the excised intestinal region. The chosen conditions enable dissolution/permeation experiments with excised rat duodenal segments. The experiments correctly predicted the superior permeation of nanosized over unmilled aprepitant that is observed in vivo.
  
  
  CONCLUSIONS
  The optimized setup uses FaSSIFmodas donor medium, excised rat duodenal sheets as permeation membrane and a receiver medium containing BSA and Antifoam B.
authors.affiliation: a Department of Pharmaceutical Technology and Biopharmaceutics , Johannes Gutenberg University , Mainz , Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Forner
authors.affiliation: b Department of Pharmacy , Uppsala University , Uppsala , Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Roos
authors.affiliation: b Department of Pharmacy , Uppsala University , Uppsala , Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Dahlgren
authors.affiliation: c Department of Biopharmaceutics, Pharmaceutical Sciences and Clinical Supply , Merck & Co. Inc ., Kenilworth , NJ , USA.
authors.forename: Filippos
authors.initials: F
authors.lastname: Kesisoglou
authors.affiliation: d Institute of Clinical and Functional Anatomy , University Medical Center Johannes Gutenberg University , Mainz , Germany.
authors.forename: Moritz A
authors.initials: MA
authors.lastname: Konerding
authors.affiliation: e Institute of Medical Biostatistics, Epidemiology and Informatics , University Medical Center Johannes Gutenberg University , Mainz , Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Mazur
authors.affiliation: b Department of Pharmacy , Uppsala University , Uppsala , Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Lennernäs
authors.affiliation: a Department of Pharmaceutical Technology and Biopharmaceutics , Johannes Gutenberg University , Mainz , Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Langguth
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry*; D018938:Caco-2 Cells / Q000737:chemistry / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology*; D006801:Humans; D007422:Intestines / Q000737:chemistry / Q000502:physiology*; D007583:Jejunum / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D012995:Solubility
chemical_list: D001647:Bile Acids and Salts
keywords: Intestinal segments; antifoaming; aprepitant; cholesterol; fasted state simulated intestinal fluid; nanosized API; rat; sink conditions