In Vivo Methods for the Assessment of Topical Drug Bioavailability

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Abstract

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described.

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Most cited references 179

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Predicting skin permeability.

R O Potts, R H Guy (1992)

Published permeability coefficient (Kp) data for the transport of a large group of compounds through mammalian epidermis were analyzed by a simple model based upon permeant size [molecular volume (MV) or molecular weight (MW)] and octanol/water partition coefficient (Koct). The analysis presented is a facile means to predict the percutaneous flux of pharmacological and toxic compounds solely on the basis of their physiocochemical properties. Furthermore, the derived parameters of the model have assignable biophysical significance, and they provide insight into the mechanism of molecular transport through the stratum corneum (SC). For the very diverse group of chemicals considered, the results demonstrate that SC intercellular lipid properties alone are sufficient to account for the dependence of Kp upon MV (or MW) and Koct. It is found that the existence of an "aqueous-polar (pore) pathway" across the SC is not necessary to explain the Kp values of small, polar nonelectrolytes. Rather, their small size, and consequently high diffusivity, accounts for their apparently larger-than-expected Kp. Finally, despite the size and breadth of the data set (more than 90 compounds with MW ranging from 18 to greater than 750, and log Koct ranging from -3 to +6), the postulated upper limiting value of Kp for permeants of very high lipophilicity cannot be determined. However, the analysis is able to define the physicochemical characteristics of molecules which should exhibit these maximal Kp values.(ABSTRACT TRUNCATED AT 250 WORDS)

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Penetration profile of microspheres in follicular targeting of terminal hair follicles.

R Toll, U Jacobi, H. Richter … (2004)

The transfollicular administration of pharmacologically active molecules is of current therapeutic interest, mainly with regard to delivery to specific sites of the hair follicle (HF) and the reduction of hepatic metabolism and systemic toxicity. HF are privileged pathways for specific molecules depending on formulations, which enter faster into these shunts than through the stratum corneum. The aim was to optimize the delivery of fluorescent microspheres into the HF, thereby, developing a standardized protocol for follicular targeting with microspheres. The number of HF showing penetration, as well as the depth of penetration, was determined. Freshly excised skin samples with terminal HF were divided into groups, with or without prior treatment with cyanoacrylate skin surface stripping-technique (CSSS). Thereafter microspheres at a size of 0.75-6.0 microm were applied according to the developed standardized protocol. Skin biopsies were obtained, shock-frozen, and sectioned in 5 microm slices. We demonstrated a selective penetration route of the microspheres into the HF. Optimal microsphere size proved to be approximately 1.5 microm, with a 55% rate of all HF, and with a maximum penetration depth of >2300 microm. Without previous CSSS treatment of the skin, the transfollicular microsphere penetration was below 27% with a maximum penetration depth of 1000 microm. Thus, the basis for follicular targeting of essential structures containing stem cells for keratinocytes, melanocytes, and mast cells has been laid.

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Homogeneous transport in a heterogeneous membrane: water diffusion across human stratum corneum in vivo.

Y.N. Kalia, F Pirot, R.H. Guy (1996)

The objective of this study was to determine whether a structurally heterogeneous biomembrane, human stratum corneum (SC), behaved as a homogeneous barrier to water transport. The question is relevant because the principal function of the SC in vivo is to provide a barrier to the insensible loss of tissue water across the skin. Impedance spectra (IS) of the skin and measurements of the rate of transepidermal water loss (TEWL) were recorded sequentially in vivo in human subjects as layers of the SC were progressively removed by the serial application of adhesive tape strips. The low-frequency (< or = 100 rad s-1) impedance of skin was much more significantly affected by tape stripping than the higher frequency values; removal of the outermost SC layer had the largest effect. In contrast, TEWL changed little as the outer SC layers were stripped off, but increased dramatically when 6-8 microns of the tissue had been removed. It follows that the two noninvasive techniques probe SC barrier integrity in somewhat different ways. After SC removal, recovery of barrier function, as assessed by increasing values of the low-frequency impedance, apparently proceeded faster than TEWL decreased to the prestripping control. The variation of TEWL as a function of SC removal behaved in a manner entirely consistent with a homogeneous barrier, thereby permitting the apparent SC diffusivity of water to be found. Skin impedance (low frequency) was correlated with the relative concentration of water within the SC, thus providing an in vivo probe for skin hydration. Finally, the SC permeability coefficient to water, as a function of SC thickness, was calculated and correlated with the corresponding values of skin admittance derived from IS.

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Author and article information

Contributors

: r.h.guy@bath.ac.uk

Journal

Journal ID (nlm-ta): Pharm Res

Title: Pharmaceutical Research

Publisher: Springer US (Boston )

ISSN (Print): 0724-8741

ISSN (Electronic): 1573-904X

Publication date (Electronic): 6 November 2007

Publication date (Print): January 2008

Volume: 25

Issue: 1

Pages: 87-103

Affiliations

[1 ]School of Pharmaceutical Sciences, University of Geneva, 30 quai E. Ansermet, CH-1211 Geneva 4, Switzerland

[2 ]Debio Recherche Pharmaceutique S.A., Route du Levant 146, CH-1920 Martigny, Switzerland

[3 ]Antares Pharma AG, Gewerbestrasse 18, 4123 Allschwil, Switzerland

[4 ]Université catholique de Louvain, Unité de pharmacie galénique, industrielle et officinale, Avenue E. Mounier 73, 1200 Brussels, Belgium

[5 ]UCB SA, Chemin du Foriest 1, 1420 Braine-l’Alleud, Belgium

[6 ]Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY Allschwil, UK

Article

Publisher ID: 9429

DOI: 10.1007/s11095-007-9429-7

PMC ID: 2217624

PubMed ID: 17985216

SO-VID: a7df9d97-26b4-4a22-a1d3-402db4ebdcc1

History

Date received : 5 June 2007

Date accepted : 24 July 2007

Custom metadata

ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: cutaneous drug concentration,cutaneous bioavailability,microdialysis,tape stripping,dermatopharmacokinetics

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ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: cutaneous drug concentration, cutaneous bioavailability, microdialysis, tape stripping, dermatopharmacokinetics

In Vivo Methods for the Assessment of Topical Drug Bioavailability

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Abstract

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Dermal Microdialysis in Pharmacokinetics

Most cited references 179

Predicting skin permeability.

Penetration profile of microspheres in follicular targeting of terminal hair follicles.

Homogeneous transport in a heterogeneous membrane: water diffusion across human stratum corneum in vivo.

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