title: Dermatopharmacokinetics: factors influencing drug clearance from the stratum corneum.
abstract: OBJECTIVE
  The dermatopharmacokinetic methodology, in which tape stripping of the stratum corneum (SC) is used to access the amount of drug accumulated in the skin barrier, has been proposed for the quantification of topical drug bioavailability. This investigation examined the clearance phase of a model drug from the SC after a short application of an infinite dose.
  
  
  METHODS
  A saturated solution of ibuprofen in propylene glycol/water was applied to the forearm of human volunteers for 30 min. The formulation was then removed and the drug profile across the SC was assessed immediately, and over the next 4 h.
  
  
  RESULTS
  The clearance phase depends only on drug diffusivity in the SC. However, the expected, progressive "flattening" of the concentration profiles with increasing time post-formulation removal was not observed. It was subsequently deduced, using infrared spectroscopy, that the rapid percutaneous diffusion of propylene glycol, relative to ibuprofen, resulted in the transient maintenance of a saturated drug concentration at the SC surface even after removal of the original formulation.
  
  
  CONCLUSIONS
  The important role of formulation excipients in topical delivery is demonstrated, and the local disposition of cosolvents within the SC may impact significantly on drug dermatopharmacokinetics and local bioavailability.
authors.affiliation: Department of Pharmacy, University of Parma, Parma, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Nicoli
authors.forename: Annette L
authors.initials: AL
authors.lastname: Bunge
authors.forename: M Begoña
authors.initials: MB
authors.lastname: Delgado-Charro
authors.forename: Richard H
authors.initials: RH
authors.lastname: Guy
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D005260:Female; D005542:Forearm; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D019946:Propylene Glycol / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects; D012997:Solvents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D055815:Young Adult
chemical_list: D012997:Solvents; D019946:Propylene Glycol; D007052:Ibuprofen