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Concentration Dependency in Nicotine Skin Penetration Flux from Aqueous Solutions Reflects Vehicle Induced Changes in Nicotine Stratum Corneum Retention

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ABSTRACT

Purpose

This study sought to understand the mechanism by which the steady state flux of nicotine across the human skin from aqueous solutions is markedly decreased at higher nicotine concentrations.

Methods

Nicotine’s steady state flux through human epidermis and its amount in the stratum corneum for a range of aqueous nicotine solutions was determined using Franz diffusion cells, with the nicotine analysed by high performance liquid chromatography (HPLC). Nicotine’s thermodynamic activity in the various solutions was estimated from its partial vapour pressure and stratum corneum hydration was determined using a corneometer. The amount of nicotine retained in the stratum corneum was estimated from the nicotine amount found in individual stratum corneum tape strips and a D-Squame determined weight for each strip.

Results

The observed steady state flux of nicotine across human epidermis was found to show a parabolic dependence on nicotine concentration, with the flux proportional to its thermodynamic activity up to a concentration of 48% w/w. The nicotine retention in the stratum corneum showed a similar dependency on concentration whereas the diffusivity of nicotine in the stratum corneum appeared to be concentration independent. This retention, in turn, could be estimated from the extent of stratum corneum hydration and the nicotine concentration in the applied solution and volume of water in the skin.

Conclusions

Nonlinear dependency of nicotine skin flux on its concentration results from a dehydration induced decrease in its stratum corneum retention at higher concentration and not dehydration induced changes nicotine diffusivity in the stratum corneum.

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors thank to Australian National Health Medical Research Council for the financial research support, Dr. Simon Gunn for assistance in redrawing the figures and Dr Peng Li for his helpful comments. RK acknowledges Indonesian Directorate of Higher Degree of Education (DIKTI) for the scholarship. Professor Michael S Roberts would like to thank to Professor Annette Bunge for providing a copy her 2-butoxyethanol poster #24 presented at the 10th Perspectives in Percutaneous Penetration (PPP) conference, La Grande Motte, France, April 19–22, 2006 France and for our discussion on her findings.

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Authors and Affiliations

  1. Therapeutics Research Centre, School of Pharmacy & Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia

    Rina Kuswahyuning & Michael S. Roberts

  2. Department of Pharmaceutics, Faculty of Pharmacy, University of Gadjah Mada, Yogyakarta, Indonesia

    Rina Kuswahyuning

  3. Therapeutics Research Centre, School of Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD, 4102, Australia

    Michael S. Roberts

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  1. Rina Kuswahyuning
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  2. Michael S. Roberts
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Correspondence to Michael S. Roberts.

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Kuswahyuning, R., Roberts, M.S. Concentration Dependency in Nicotine Skin Penetration Flux from Aqueous Solutions Reflects Vehicle Induced Changes in Nicotine Stratum Corneum Retention. Pharm Res 31, 1501–1511 (2014). https://doi.org/10.1007/s11095-013-1256-4

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  • DOI: https://doi.org/10.1007/s11095-013-1256-4

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