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Dermatopharmacokinetics: Factors Influencing Drug Clearance from the Stratum Corneum

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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.

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Acknowledgments

We thank Dr. Sandra Wiedersberg for very helpful discussion and advice.

Author information

Authors and Affiliations

  1. Department of Pharmacy, University of Parma, Parma, Italy

    Sara Nicoli

  2. Department of Chemical Engineering, Colorado School of Mines, Golden, Colorado, USA

    Annette L. Bunge

  3. Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK

    M. Begoña Delgado-Charro & Richard H. Guy

Authors
  1. Sara Nicoli
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  2. Annette L. Bunge
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  3. M. Begoña Delgado-Charro
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  4. Richard H. Guy
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Corresponding author

Correspondence to Richard H. Guy.

Appendix

Appendix

The concentration of drug in the stratum corneum (SC) during clearance is described by Fick’s second law:

$$\frac{{\partial C}}{{\partial t}} = D\frac{{\partial ^2 C}}{{\partial x^2 }}$$
(3)

where the concentration at time t app is defined by Eq. 1, the flux of drug from the surface of the stratum corneum is zero, and sink conditions apply at the interface between the SC and viable epidermis:

$$\begin{aligned} & \frac{{\partial C}}{{\partial x}} = 0\quad \quad {\text{at}}\,x = 0 \\ & \;\;C = 0\quad \quad {\text{at}}\,x = L \\ \end{aligned}$$

Equation 3 is solved for these boundary conditions by separation of variables to obtain Eq. 2 (19).

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Nicoli, S., Bunge, A.L., Delgado-Charro, M.B. et al. Dermatopharmacokinetics: Factors Influencing Drug Clearance from the Stratum Corneum. Pharm Res 26, 865–871 (2009). https://doi.org/10.1007/s11095-008-9785-y

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  • DOI: https://doi.org/10.1007/s11095-008-9785-y

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