title: Permeability assessment for solid oral drug formulations based on Caco-2 monolayer in combination with a flow through dissolution cell.
abstract: The aim of our study was to develop an apparatus assessing in vitro permeation through Caco-2 monolayers of oral solid dosage forms as a possible tool to forecast in vivo performance. Therefore, flow through dissolution and permeation modules were connected by means of a stream splitter. Permeation was measured in a specially designed cell, dissolution took place in the apparatus 4, USP. In order to test the apparatus for its reproducibility and conclusiveness, different tablet strengths and varying release profiles of propranolol HCl tablets were produced and evaluated. It was shown that for both tablet species, immediate and extended release, the apparatus was able to measure permeation through Caco-2 monolayer as well as dissolution simultaneously with high precision and reproducibility. The permeated amount of the three immediate release tablets with increasing dosage strength showed linear dependency on the dosage strength. Furthermore, the effect of retarded release on permeation could be detected and conclusive data for dissolution and permeation were obtained. In summary, connecting cell culture based permeability assessment with compendial flow through dissolution equipment led to promising results and poses the base for more advanced studies for detecting influences of dosage forms on permeation process.
authors.affiliation: Saarland University, Biopharmaceutics and Pharmaceutical Technology, Saarbrücken, Germany.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Motz
authors.forename: Ulrich F
authors.initials: UF
authors.lastname: Schaefer
authors.forename: Stefan
authors.initials: S
authors.lastname: Balbach
authors.forename: Thomas
authors.initials: T
authors.lastname: Eichinger
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008689:Methacrylates / Q000737:chemistry; D008954:Models, Biological; D011108:Polymers / Q000737:chemistry; D011433:Propranolol / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
chemical_list: D003692:Delayed-Action Preparations; C477853:Eudragit NE 30-D; D005079:Excipients; D008689:Methacrylates; D011108:Polymers; D013607:Tablets; D011433:Propranolol