Category: Clinical Pharmacology
Purpose: The site of action for topical dermatological drug products is in the skin and/or in the surrounding local tissues. Therefore, the local bioavailability of such products may be relevant for evaluating bioequivalence. Tape stripping is a relatively non-invasive methodology that can be used to determine the local skin bioavailability of a drug, but to our knowledge the variability and reproducibility of tape stripping from different operators have not been investigated. In order to evaluate operator differences, two lidocaine and two diclofenac products were used as model compounds. In addition, two different operators (operators 1 and 2) were used for collecting data from each volunteer.
Methods: Two different commercially available lidocaine topical delivery system (TDS), 5% products (Lidocaine A and B, 140 cm2 each) and diclofenac topical products (diclofenac TDS, 1.3% [A] and diclofenac topical solution, 2% [B]) were evaluated. Two separate clinical studies (lidocaine and diclofenac) were conducted with twelve planned volunteers per study. For the two studies, the tape stripping session consisted of applying Products A and B to three sites on each volar forearm of each volunteer. For each site, a TDS piece cut to approximately 8.25 cm2 or 10 mg/cm2 of solution spread over 8.25 cm2 was applied. Locations of the applied products were randomized to one of six sites. The products were removed and skin surface cleaned from each site following the uptake time point (lidocaine: 10 h post application; diclofenac A: 10 h post application; diclofenac B: 6 h post application). A 5 cm2 section of each site was tape stripped to determine the amount of drug in the stratum corneum (SC) at each designated time point (uptake, clearance 1 [lidocaine: 5 h post removal; diclofenac: 17 h post removal] and clearance 2 [lidocaine: 14 h post removal; diclofenac: 41 h post removal]). Each site was tape stripped for a minimum of 12 tape strips up to a maximum of either 30 tape strips or when the site reached 6x the baseline transepidermal water loss (TEWL) value, determined using a Delfin VapoMeter. Successive tape strips were grouped together based on a combined SC weight of at least 750 μg or 6 tapes, whichever came first. API was extracted from the skin tape strip groups with methanol and analyzed using a validated high pressure liquid chromatography (HPLC) method.
Results: Results from twelve volunteers from the lidocaine study and eight volunteers from the diclofenac study of a planned twelve volunteer study have been collected and are reported in Tables 1 and 2. Drug amounts were highest in the uptake phase and decreased at each subsequent clearance phase. Overall operator 2 removed less skin compared to operator 1 in the lidocaine study but that was not observed in the diclofenac study.
Conclusion: Twenty volunteers (lidocaine: n=12; diclofenac: n=8) have completed the studies to date. The comparison of results between the operators showed a similar skin clearance, tape strip skin amount removed and tape strip drug amount extracted following tape stripping for both drugs. From the results, it appears that the majority of the 90% confidence intervals for the skin mass ratios are close to 1.0 indicating good reproducibility on the amount of skin removed following tape stripping. The ability to remove a similar amount of skin between operators during tape stripping as observed is vital and can potentially have a significant impact on the final results and conclusion of a study. These are promising results and show that it is possible to perform tape stripping with multiple operators without increasing variability
Sherin Thomas– PhD Candidate, University of Maryland, Baltimore, Maryland
Dana Hammell– Research Fellow, University of Maryland, Baltimore, Baltimore, Maryland
Annette Bunge– Colorado School of Mines, Golden, Colorado
Hazem Hassan– Baltimore, Maryland
Audra Stinchcomb– Professor, University of Maryland Baltimore, Baltimore, Maryland