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        Overcoming the nail barrier : A systematic investigation of ungual chemical penetration enhancement

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        IJP 2009 final draft.pdf (PDF, 233Kb)
        Author
        Brown, Marc
        Khengar, Rajeshree H.
        Turner, Rob B.
        Forbes, B.
        Traynor, M.J.
        Evans, C.R.G.
        Jones, S. A.
        Attention
        2299/3646
        Abstract
        This study investigated the in vitro nail permeability of penetrants of varying lipophilicity—caffeine (CF, log P −0.07), methylparaben (MP, log P 1.96) and terbinafine (TBF, log P 3.3) and the effect of 2 novel penetration enhancers (PEs), thioglycolic acid (TA) and urea hydrogen peroxide (urea H2O2) on their permeation. Studies were conducted using full thickness human nail clippings and ChubTur® diffusion cells and penetrants were applied as saturated solutions. The rank order of steady-state penetrant flux throughnails without PE application(MP > CF > TBF) suggesteda greater sensitivity to penetrant molecular weight rather than log P. TA increased the flux of CF and MP ∼4- and ∼2-fold, respectively, whilst urea H2O2 proved ineffective at enhancing permeability. The sequential application of TA followed by urea H2O2 increased TBF and CF flux (∼19- and ∼4-fold, respectively) but reversing the application order of the PEs was only mildly effective at increasing just MP flux (∼2-fold). Both nail PEs are likely to function via disruption of keratin disulphide bonds and the associated formation of pores that provide more ‘open’ drug transport channels. Effects of the PEs were penetrant specific, but the use of a reducing agent (TA) followed by an oxidising agent (urea H2O2) dramatically improved human nail penetration.
        Publication date
        2009-03-31
        Published in
        International Journal of Pharmaceutics
        Published version
        https://doi.org/10.1016/j.ijpharm.2008.11.009
        Other links
        http://hdl.handle.net/2299/3646
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        School of Life and Medical Sciences
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