title: Characterization and evaluation of a modified PVPA barrier in comparison to Caco-2 cell monolayers for combined dissolution and permeation testing.
abstract: Aim of this study was to implement a modified phospholipid vesicle-based permeation assay (PVPA) barrier as alternative to Caco-2 cell monolayers in a combined dissolution and permeation system for testing of solid dosage forms. Commercially available Transwell® inserts were coated with egg phospholipids (Lipoid E 80) and characterized by confocal Raman microscopy. The modified PVPA barrier was then evaluated in permeation studies with solutions of different drugs as well as in combined dissolution and permeation studies utilizing an immediate and an extended release tablet formulation. Raman cross section images demonstrated complete filling of the membrane pores with lipids and the formation of a continuous lipid layer of increasing thickness on top of the membrane during the stepwise coating procedure. Furthermore, it could be shown that this lipid coating remains intact for at least 18h under dynamic flow conditions, significantly exceeding the viability of Caco-2 cell monolayers. Permeability data for both drug solutions as well as for a fast and slow release tablet formulation were in excellent correlation with those data obtained for Caco-2 cell monolayers. Especially under the dynamic flow conditions prevailing in such a setup, the modified PVPA barrier is more robust and easier to handle than epithelial cell monolayers and can be prepared rather easily at a fraction of costs and time. The modified PVPA barrier may therefore represent a valuable alternative to Caco-2 cell monolayers in such context.
authors.affiliation: Saarland University, Department of Biopharmaceutics and Pharmaceutical Technology, Campus A4.1, 66123 Saarbruecken, Germany. Electronic address: s.gantzsch@mx.uni-saarland.de.
authors.forename: Sandra P
authors.initials: SP
authors.lastname: Gantzsch
authors.affiliation: Saarland University, Department of Biopharmaceutics and Pharmaceutical Technology, Campus A4.1, 66123 Saarbruecken, Germany. Electronic address: birthe.kann@mx.uni-saarland.de.
authors.forename: Birthe
authors.initials: B
authors.lastname: Kann
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Lead Generation to Candidate Realization, Industriepark Hoechst, 65926 Frankfurt/Main, Germany. Electronic address: Monika.Ofer-Glaessgen@sanofi.com.
authors.forename: Monika
authors.initials: M
authors.lastname: Ofer-Glaessgen
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Lead Generation to Candidate Realization, Industriepark Hoechst, 65926 Frankfurt/Main, Germany. Electronic address: Petra.Loos@sanofi.com.
authors.forename: Petra
authors.initials: P
authors.lastname: Loos
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Lead Generation to Candidate Realization, Industriepark Hoechst, 65926 Frankfurt/Main, Germany. Electronic address: Harald.Berchtold@sanofi.com.
authors.forename: Harald
authors.initials: H
authors.lastname: Berchtold
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Lead Generation to Candidate Realization, Industriepark Hoechst, 65926 Frankfurt/Main, Germany. Electronic address: Stefan.Balbach@sanofi.com.
authors.forename: Stefan
authors.initials: S
authors.lastname: Balbach
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Lead Generation to Candidate Realization, Industriepark Hoechst, 65926 Frankfurt/Main, Germany. Electronic address: Thomas.Eichinger@sanofi.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Eichinger
authors.affiliation: Saarland University, Department of Biopharmaceutics and Pharmaceutical Technology, Campus A4.1, 66123 Saarbruecken, Germany; Helmholtz Centre for Infection Research and Helmholtz Institute for Pharmaceutical Research Saarland, Department of Drug Delivery, Campus A4.1, 66123 Saarbruecken, Germany. Electronic address: lehr@mx.uni-saarland.de.
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
authors.affiliation: Saarland University, Department of Biopharmaceutics and Pharmaceutical Technology, Campus A4.1, 66123 Saarbruecken, Germany. Electronic address: ufs@mx.uni-saarland.de.
authors.forename: Ulrich F
authors.initials: UF
authors.lastname: Schaefer
authors.affiliation: Saarland University, Department of Biopharmaceutics and Pharmaceutical Technology, Campus A4.1, 66123 Saarbruecken, Germany; Helmholtz Centre for Infection Research and Helmholtz Institute for Pharmaceutical Research Saarland, Department of Drug Delivery, Campus A4.1, 66123 Saarbruecken, Germany. Electronic address: m.windbergs@mx.uni-saarland.de.
authors.forename: Maike
authors.initials: M
authors.lastname: Windbergs
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D008567:Membranes, Artificial; D018613:Microscopy, Confocal; D010539:Permeability; D010743:Phospholipids / Q000378:metabolism*; D012995:Solubility; D013607:Tablets
chemical_list: D003692:Delayed-Action Preparations; D008567:Membranes, Artificial; D010743:Phospholipids; D013607:Tablets
keywords: Artificial membrane; Confocal Raman microscopy; Controlled release; Permeability; Solid oral dosage forms; Three dimensional imaging