title: Ionisation and the effect of absorption enhancers on transport of salicylic acid through silastic rubber and human skin.
abstract: OBJECTIVE
  to investigate if salicylic acid (SA)-permeation through excised human skin (HS) and silastic rubber (SR) conforms to the pH-hypothesis and to assess the influence of a range of absorption enhancers on the transport of SA with and without a transmembrane pH-gradient.
  
  
  METHODS
  Franz cells were used to study SA permeation from solutions and saturated suspensions. McIlvaine buffers were used to maintain transmembrane pH-gradients. Membrane pretreatment was used to study the action of absorption enhancers.
  
  
  RESULTS
  the flux of SA from solutions was dependent upon the vehicle pH and permeant concentration was directly related to the degree of ionisation of the solute. Flux from suspensions was independent of pH, since the level of unionised drug, the predominant diffusing species, was maintained at the intrinsic saturated solubility at all pH values. The observed SA flux enhancement across human skin without a transmembrane pH-gradient was not significantly different from the enhancement with a pH-gradient for all of the absorption enhances used, except for dodecylamine.
  
  
  CONCLUSIONS
  the results showed that SA permeation conformed to the p H-partition hypothesis. The evidence from absorption-enhancer pretreatment demonstrated that, under certain conditions, the transdermal penetration enhancement of a number of topical enhancing compounds, including Azone and oleic acid can be explained without recourse to ion-pair phenomena.
authors.affiliation: Drug Delivery Research Group, Pharmaceutical Sciences Research Institute, Aston University, Birmingham, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Smith
authors.forename: W J
authors.initials: WJ
authors.lastname: Irwin
mesh_terms: D000042:Absorption; D020099:Coated Materials, Biocompatible; D004058:Diffusion; D004129:Dimethylpolysiloxanes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D020156:Salicylic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D012828:Silicones; D012869:Skin Absorption / Q000187:drug effects*; D012996:Solutions
chemical_list: D020099:Coated Materials, Biocompatible; D004129:Dimethylpolysiloxanes; D007202:Indicators and Reagents; D012828:Silicones; D012996:Solutions; C013830:baysilon; D020156:Salicylic Acid