Dermatopharmacokinetics: Factors Influencing Drug Clearance from the Stratum Corneum
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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.
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.
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.
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 WORDSclearance dermatopharmacokinetics infrared spectroscopy stratum corneum topical bioavailability
We thank Dr. Sandra Wiedersberg for very helpful discussion and advice.
- 1.HHS, FDA, and CDER. Topical dermatological drug product NDAs and ANDAs—in vivo bioavailability, bioequivalence, in vitro release and associated studies Draft Guidance for Industry. (1998).Google Scholar
- 3.L. K. Pershing, J. L. Nelson, J. L. Corlett, S. P. Shrivastava, D. B. Hare, and V. P. Shah. Assessment of dermatopharmacokinetic approach in the bioequivalence determination of topical tretinoin gel products. J Am Acad Dermatol. 48:740–751 (2003) doi: 10.1067/mjd.2003.175.PubMedCrossRefGoogle Scholar
- 7.M. Breternitz, M. Flach, J. Prassler, P. Elsner, and J. W. Fluhr. Acute barrier disruption by adhesive tapes is influenced by pressure, time and anatomical location: integrity and cohesion assessed by sequential tape stripping. A randomized, controlled study. Br J Dermatol. 156:231–240 (2007) doi: 10.1111/j.1365-2133.2006.07632.x.PubMedCrossRefGoogle Scholar
- 13.J. Lademann, A. Ilgevicius, O. Zurbau, H. D. Liess, S. Schanzer, H. J. Weigmann, C. Antoniou, R. V. Pelchrzim, and W. Sterry. Penetration studies of topically applied substances: optical determination of the amount of stratum corneum removed by tape stripping. J Biomed Opt. 11:054026 (2006) doi: 10.1117/1.2359466.PubMedCrossRefGoogle Scholar
- 14.B. N'Dri-Stempfer, W. C. Navidi, R. H. Guy, and A. L. Bunge. Improved Bioequivalence Assessment of Topical Dermatological Drug Products Using Dermatopharmacokinetics. Pharm Res (2008) doi: 10.1007/s11095-008-9742-9.
- 18.S. Wiedersberg, C. S. Leopold, and R. H. Guy. Dermatopharmacokinetics of betamethasone 17-valerate: Influence of formulation viscosity and skin surface cleaning procedure. Eur J Pharm Biopharm (2008) doi: 10.1016/j.ejpb.2008.10.001.
- 19.S. Wiedersberg, A. Naik, C. S. Leopold, and R. H. Guy. Pharmacodynamics and dermatopharmacokinetics of betamethasone 17-valerate: assessment of topical bioavailability. Br J Dermatol (2008) doi: 10.1111/j.1365-2133.2008.08757.x.
- 26.M. Pellett, A. Watkinson, J. Hadgraft, and K. Brain. Comparison of permeability data from traditional diffusion cells and ATR-FTIR spectroscopy. Part II: determination of diffusional pathlengths in synthetic membranes and human stratum corneum. Int. J. Pharm. 154:217–227 (1997) doi: 10.1016/S0378-5173(97)00143-9.CrossRefGoogle Scholar
- 29.H. S. Carslaw, and J. C. Jaeger. Conduction of Heat in Solids. Oxford University Press, Oxford, 1959, pp. 92–110.Google Scholar