derma to kinetic

7/28/2019 Derma to Kinetic

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http://www.pharmabiz.com/PrintArticle.aspx?aid=65665&sid=0

Tape stripping in pharmacokinetic studies

Rekha Rao, Sanju Nanda and Rakesh Pahwa, Thursday, October 20, 2011, 08:00 Hrs [IST]

Topical bioavailability can be estimated from the drug concentration within the stratum corneum, which

is expected to be related to the drug concentration at the target site( i.e. usually viable epidermis or

dermis) since the stratum corneum is the rate limiting barrier layer for percutaneous absorption.

Similarly, to the determination of the drug concentration in blood and/or urine as surrogate for the

concentration at the target tissue, the determination of the drug concentration in the stratum corneum

may serve as a surrogate for the concentration in the viable epidermis. Tape stripping, which enables

the removal of the stratum corneum layer by layer, is a useful dermato-pharmacokinetic technique for

the assessment of drug amounts in stratum corneum as a function of time.

Tape stripping of the stratum corneum from the skin is a relatively non-invasive and useful technique

that has been used widely in recent years for bioavailability and dermatopharmacokinetic studies of

topically-applied drugs. The numerous problems associated with the standardization of the tape

stripping methodology have been documented at length. The general technique used to date involves

topical dosing, followed by application and subsequent removal of adhesive tape strips from the skin;

corneocytes adhering to the tape strips are thereby removed from the underlying tissue. Each tape used

in the stripping process (often 30-50 strips in total from each stripped skin site) is usually then solvent

extracted to isolate the analyte of interest, prior to high sensitivity analysis. However, the adhesive tape

stripping of the stratum corneum is not a linear process in terms of the thickness of the layer of

corneocytes removed from one strip to the next, and is not uniform in thickness across the entire field

of each tape area. This procedure, therefore, relates the mass of permeant found on each strip to the

tape strip number analyzed, and not (strictly) to stratum corneum depth or volume.

Tape stripping is used in various fields of cutaneous biology like

to evaluate barrier function to investigate dermatopathologies such as inflammatory or neoplastic disorders or neoplastic

disorders

to monitor gene expression to investigate pH profiles to evaluate animal skin as a surrogate for human skin

A disadvantage of the tape stripping method is that the amount of the corneocytes taken changes per

stripping in depence on the test persons. Furthermore, the type of substance applied and the

penetration time have an influence on the amount of corneocytes on the individual tapes. Thus, a

qualitative and quantitative determination of the penetration kinetics in relation to the profile of horny

layer is not possible.


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Quantification of drugs in tape-strips

Sequential tape stripping of the stratum corneum allows horizontal fractions of the membrane to be

obtained. The tape strips must then be extracted to recover and quantify the absorbed drug. Local

bioavailability may be assessed either from the combined tape strips, or from the individual tape-strips.

The method of quantification depends, of course, on the nature of the drug and the amount present onthe tape-strips. Various approaches have been used ranging from UV-VIS spectrophotometry, HPLC, gas

chromatography, scintillation counting and infra-red spectroscopy. The key criteria are that the

extraction process does not degrade the drug, that is efficient and reproducible, and that it is free from

interference from components of the SC and the tape adhesive. Quantification of the drug in the

combined tape-strips enables the total amount in the stratum corneum to be determined.

Issues to be resolved

Despite the clear value of a dermatokinetic approach based on tape stripping, there remains work to be

done before its usefulness can be fully exploited.

Firstly, method has to be validated appropriately via clear demonstrations that significant differences in

drug uptake into normal stratum corneum translates into clinically distinguishable scenarios in the real

world.

Second, the procedures to be followed, and the dermatokinetic protocol a simple itself, have to be at

least partially standardized. Quantification of the stratum corneum removed is mandatory and there is

an important need to develop a simple and rapid method for this purpose. With such knowledge,

complete removal of the stratum corneum is not necessary for comparative purposes, thereby allowing

for a less invasive procedure.

Third, the question of spatial localization of drug must be addressed; specifically, it has been recognized

that the target for certain drugs may be a skin appendage like hair follicle or sebaceous gland and that

particular formulations have been proposed for optimization of delivery of these structures.

Finally, there is the question of the relevance of the approach which has been developed for use on

normal skin, to drug performance on diseased skin. In part, this relates to the validation issue discussed

above and the need to correlate dermatokinetic measurements with clinical outcome.

Conclusion

Despite the fact that most pharmacologic events take place in tissues, pharmacokinetic data is usually

based on blood or serum concentrations. However, free, unbound drug concentrations can differ

significantly between blood and tissues. Measurement of free active drug concentrations in the tissue of

interest is consequently the most rational approach but has frequently been restricted by insufficient

sampling/analysis techniques.


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With tape stripping, a well accepted relatively non-invasive sampling technique that is able to sample

free, active drug directly extracellular space fluid of tissues has become available. The resulting tissue

concentration-time profile reflects both rate and extent of drug absorption from the respective

application site and can, therefore, be used for bioavailability and bioequivalence assessment.

The tape stripping method combined with the spectroscopic determination of the amount ofcorneocytes was taken up by the FDAs Guidance for Industry-Topical Dermatological drug Product

NDAs and ANDAs In Vivo Bioavailability, Bioequivalence, In Vitro Release, And Associated Studies as

recommended test method.

(Dr. Rekha Rao is lecturer in Department of Pharmaceutical Sciences, M.M.University, Mullana, Ambala,

Dr. Sanju Nanda is Reader at Department of Pharmaceutical Sciences, M.D.University, Rohtak and

Rakesh Pahwa is Assistant Prof. at Department of Pharmaceutical Sciences, Kurukshetra University.)

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