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    Evaluation of skin tape stripping in healthy human volunteers as a methodology for quantifying local drug bioavailability from dermal products

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    Author
    Shukla, Sagar cc
    Advisor
    Stinchcomb, Audra L.
    Hassan, Hazem
    Date
    2020
    Type
    dissertation
    
    Metadata
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    Abstract
    Stratum corneum (SC) tape stripping is a valuable methodology that has been used for quantifying bioavailability (BA) of topical drug products at the site of action. Although the Food and Drug Administration (FDA) tape stripping guidance was withdrawn several years ago due to variable results, with an appropriate study design, tape stripping procedures can be a reproducible BA method. Therefore, the objective of this work was to investigate the use of tape stripping to quantify BA and evaluate in vitro/in vivo correlations (IVIVC) of two model compounds (lidocaine and diclofenac). These compounds were selected for their differing physicochemical properties and skin permeation rates. Two healthy human volunteer pharmacokinetic and tape stripping studies were conducted to quantify the BA in the SC and measure the elimination rate constant through the skin (kesc). Investigator variability from the in vivo tape stripping study was also examined, and the method variability potentially induced by the investigator can be mitigated by the quality by design (QBD) approach of using transepidermal water loss (TEWL) for determining when most of the SC has been removed in each individual volunteer. TEWL readings assisted the investigator by representing the SC tape stripping endpoint, and the SC masses removed from each volunteer were similar for the two investigators. Harmonized IVPT studies were also conducted and key parameter estimates were determined (absolute bioavailability (F) and (kesc)). These parameter estimates were used to simulate in vivo SC drug concentrations. The error in the SC drug concentration predictions from both in vivo studies was usually less than 20% compared to observed values, which demonstrates the predictive power of carefully harmonized IVPT studies. IVPT studies require less time and expense than human studies, and therefore these models play an important role in the early stages of drug development to predict in vivo SC drug concentrations, and absorption of drug through the skin. In this study, in vivo kesc for a quickly permeating drug (lidocaine) appears to be well predicted by IVPT; however, further work needs to be done to predict a slowly permeating drug’s (diclofenac) SC drug concentrations and kesc.
    Description
    2020
    Pharmaceutical Sciences
    University of Maryland, Baltimore
    Ph.D.
    Keyword
    tape stripping
    Diclofenac
    Lidocaine
    Pharmacokinetics
    Pharmacology, Clinical
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/13074
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    Theses and Dissertations School of Pharmacy
    Theses and Dissertations All Schools

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