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        Understanding heat facilitated drug transport across human epidermis

        Author
        Wood, D.G.
        Brown, Marc
        Jones, S.A.
        Attention
        2299/9999
        Abstract
        The application of moderate heat is a safe and effective means to increase drug transport across human skin. However, the cascade of events that follows the exposure of a topical skin formulation to a heating source is not well understood. The aim of this study was to elucidate how three potential rate limiting stages in the drug transport process; formulation release, drug partitioning and epidermal diffusion, responded to changes in local temperature using the model drug lidocaine. Release from the formulation measured using regenerated cellulose membrane was shown to be driven by drug diffusion in the vehicle; it responded linearly when the local temperature was changed (21.6 μg/cm2/h for every 1 °C rise) and displayed no measurable partitioning of lidocaine into RCM. Once the drug was within the human epidermis, the structural changes of the barrier controlled its transport. The apparent lidocaine diffusion coefficient through silicone membrane increased from 6.52 to 8.43 × 10−4 over the 32–45 °C temperature range, but it increased from 7.74 × 10−5 cm2 h−1 to 4.8 × 10−4 cm2 h−1 in the human epidermis. In the absence of large increases in drug partitioning, fluidisation of the lipids in the upper layers of the epidermis at 37–45 °C was shown to facilitate lidocaine diffusion which for human skin transport was the rate limiting process.
        Publication date
        2012-08-01
        Published in
        European Journal of Pharmaceutics and Biopharmaceutics
        Published version
        https://doi.org/10.1016/j.ejpb.2012.03.019
        Other links
        http://hdl.handle.net/2299/9999
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