title: Ionisation effects on the permeation of pharmaceutical compounds through silicone membrane.
abstract: Silicone membrane is frequently used as an in vitro skin mimic whereby experiments incorporate a range of buffered media which may vary in pH. As a consequence of such variability in pH there is a corresponding variability in the degree of ionisation which in turn, could influence permeation through the mainly hydrophobic-rich membrane structure. This study reports the effect of pH on the permeation of five model compounds (benzoic acid, benzotriazole, ibuprofen, ketoprofen and lidocaine). For the five compounds analysed, each at three distinct percentages of ionisation, it was found that the greater extent of permeation was always for the more 'neutral', i.e. more greatly unionised, species rather than the anionic or cationic species. These findings fit with the theory that the hydrophobic membrane encourages permeation of 'lipid-like' structures, i.e. the more unionised form of compounds. However, results obtained with an Inverse Gas Chromatography Surface Energy Analyser (iGC SEA) indicate the membrane surface to be an electron dense environment. In the knowledge that unionised forms of compounds permeate (rather than the charged species) this negatively charged surface was not anticipated, i.e. the basic membrane surface did not appear to affect permeation.
authors.affiliation: Department of Pharmacy, School of Applied Science, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK. Electronic address: l.waters@hud.ac.uk.
authors.forename: L J
authors.initials: LJ
authors.lastname: Waters
authors.affiliation: Department of Pharmacy, School of Applied Science, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.
authors.forename: A K M M H
authors.initials: AKMMH
authors.lastname: Bhuiyan
mesh_terms: D019817:Benzoic Acid / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002849:Chromatography, Gas / Q000379:methods; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000737:chemistry; D007477:Ions / Q000737:chemistry*; D007660:Ketoprofen / Q000737:chemistry; D008012:Lidocaine / Q000737:chemistry; D008567:Membranes, Artificial; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012825:Silicon / Q000737:chemistry*; D013499:Surface Properties; D014230:Triazoles / Q000737:chemistry
chemical_list: D007477:Ions; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D014230:Triazoles; C012771:benzotriazole; D019817:Benzoic Acid; D007660:Ketoprofen; D008012:Lidocaine; D007052:Ibuprofen; D012825:Silicon
keywords: Ionisation; PDMS; Permeation; Silicone; Transdermal; pK(a)