title: Probing the effect of vehicles on topical delivery: understanding the basic relationship between solvent and solute penetration using silicone membranes.
abstract: OBJECTIVE
  In the present study we examined the relationship between solvent uptake into a model membrane (silicone) with the physical properties of the solvents (e.g., solubility parameter, melting point, molecular weight) and its potential predictability. We then assessed the subsequent topical penetration and retention kinetics of hydrocortisone from various solvents to define whether modifications to either solute diffusivity or partitioning were dominant in increasing permeability through solvent-modified membranes.
  
  
  METHODS
  Membrane sorption of solvents was determined from weight differences following immersion in individual solvents, corrected for differences in density. Permeability and retention kinetics of 3H-hydrocortisone, applied as saturated solutions in the various solvents, were determined over 48 h in horizontal Franz-type glass diffusion cells.
  
  
  RESULTS
  Solvent sorption into the membrane could be related to differences in solubility parameters, MW and hydrogen bonding (r2=0.76). The actual and predicted volume of solvent sorbed into the membrane was also found to be linearly related to Log hydrocortisone flux, with changes in both diffusivity and partitioning of hydrocortisone observed for the different solvent vehicles.
  
  
  CONCLUSIONS
  A simple structure-based predictive model can be applied to the sorption of solvents into silicone membranes. Changes in solute diffusivity and partitioning appeared to contribute to the increased hydrocortisone flux observed with the various solvent vehicles. The application of this predictive model to the more complex skin membrane remains to be determined.
authors.affiliation: Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: S E
authors.initials: SE
authors.lastname: Cross
authors.forename: W J
authors.initials: WJ
authors.lastname: Pugh
authors.forename: J
authors.initials: J
authors.lastname: Hadgraft
authors.forename: M S
authors.initials: MS
authors.lastname: Roberts
mesh_terms: D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000493:pharmacokinetics; D006854:Hydrocortisone / Q000737:chemistry / Q000493:pharmacokinetics; D008567:Membranes, Artificial; D014677:Pharmaceutical Vehicles / Q000737:chemistry* / Q000493:pharmacokinetics; D012828:Silicones / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D012997:Solvents / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D000893:Anti-Inflammatory Agents; D008567:Membranes, Artificial; D014677:Pharmaceutical Vehicles; D012828:Silicones; D012997:Solvents; D006854:Hydrocortisone