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        A fundamental investigation into the effects of eutectic formation on transmembrane transport

        Author
        Fiala, Sarah
        Jones, Stuart A.
        Brown, Marc
        Attention
        2299/5501
        Abstract
        Eutectic systems enhance the permeation of therapeutic agents across biological barriers, but the mechanism by which this occurs has not previously been elucidated. Using human skin it has proven difficult to isolate the fundamental effects of eutectic formation on molecule diffusion and partition from those that arise as a consequence of the simultaneous application of two agents. The aim of this work was to employ a model hydrophobic membrane to understand the fundamental permeation characteristics of two agents when applied as a eutectic mixture. Lidocaine and prilocaine were selected as model agents and infinite-dose permeation studies were carried out using pre-calibrated Franz diffusion cells with two thicknesses of silicone membrane. Membrane solubility was determined by HCl solution extraction and the membrane diffusion coefficients were calculated from the permeation lag-times. The maximum permeation enhancement was achieved using a eutectic mixture at a 0.7:0.3 prilocaine/lidocaine ratio. A higher solubility of both agents in silicone membrane, enhanced diffusivity of prilocaine and superior release of both drugs, all contributed to produce enhanced permeation from the eutectic mixtures. Deconvolution of the transmembrane transport process suggests that the eutectic enhancement phenomena is a consequence of more favorable permeation characteristics of the two molecules in the absence of a formulation vehicle which competes in the transport process. (c) 2010 Elsevier B.V. All rights reserved.
        Publication date
        2010-06-30
        Published in
        International Journal of Pharmaceutics
        Published version
        https://doi.org/10.1016/j.ijpharm.2010.04.001
        Other links
        http://hdl.handle.net/2299/5501
        Relations
        School of Life and Medical Sciences
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