Pharmaceutical Research

, Volume 26, Issue 4, pp 865–871

Dermatopharmacokinetics: Factors Influencing Drug Clearance from the Stratum Corneum

  • Sara Nicoli
  • Annette L. Bunge
  • M. Begoña Delgado-Charro
  • Richard H. Guy
Research Paper

DOI: 10.1007/s11095-008-9785-y

Cite this article as:
Nicoli, S., Bunge, A.L., Delgado-Charro, M.B. et al. Pharm Res (2009) 26: 865. doi:10.1007/s11095-008-9785-y

Abstract

Purpose

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.

KEY WORDS

clearance dermatopharmacokinetics infrared spectroscopy stratum corneum topical bioavailability 

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Sara Nicoli
    • 1
  • Annette L. Bunge
    • 2
  • M. Begoña Delgado-Charro
    • 3
  • Richard H. Guy
    • 3
  1. 1.Department of PharmacyUniversity of ParmaParmaItaly
  2. 2.Department of Chemical EngineeringColorado School of MinesGoldenUSA
  3. 3.Department of Pharmacy and PharmacologyUniversity of BathBathUK

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