Pharmaceutical Research

, Volume 24, Issue 12, pp 2207–2212 | Cite as

Nail Swelling as a Pre-formulation Screen for the Selection and Optimisation of Ungual Penetration Enhancers

  • R. H. Khengar
  • S. A. JonesEmail author
  • R. B. Turner
  • B. Forbes
  • M. B. Brown
Research Paper



Targeting drug treatment to fungal infections that reside within or below the nail plate is problematic due to the highly restrictive barrier of the human nail. To optimise topical formulations for ungual drug delivery, inclusion of an effective penetration enhancer (PE) is imperative. At present, in vitro nail permeation studies can take weeks or months in order to obtain any meaningful data because the lack of a simple in vitro model to identify and develop nail PEs makes the selection and optimisation of novel PEs an empirical and inefficient process. The aim of this study was to compare three methods for pre-formulation screening of putative ungual PEs and then to select the most suitable technique for screening candidates that may enhance the permeation of therapeutic agents through the human nail.


Three screening techniques were evaluated; nail swelling (weight increase of human nail clippings), horse hoof swelling (weight increase of horse hoof clippings) and nail penetration of a radiolabelled permeability probe. Four test PEs were evaluated using each screening method and nail swelling was identified as a simple, rapid, economic, relevant and reliable technique. This screen was then used to evaluate 20 potential PEs. Thioglycolic acid (TA), hydrogen peroxide (H2O2) and urea H2O2 produced the greatest nail weight increases; 71.0 ± 4.6%, 69.2 ± 6.6%, and 69.0 ± 9.9 respectively. To confirm the relationship between human nail swelling and altered ungual barrier function, a permeation study was performed in human nails using caffeine as a model penetrant.

Results and Discussion

Human nails pre-treated with TA in vitro had a 3.8-fold increase in caffeine flux compared to the control (TA-free solution). This study illustrated the potential to use human nail clipping swelling as a surrogate marker of PE activity for topical ungual drug delivery.

Key words

nail onychomycosis penetration enhancers ungual water uptake 



Thank you to MedPharm Ltd for financial support.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • R. H. Khengar
    • 1
  • S. A. Jones
    • 1
    Email author
  • R. B. Turner
    • 2
  • B. Forbes
    • 1
  • M. B. Brown
    • 2
    • 3
  1. 1.Pharmaceutical Science Research DivisionKing’s College LondonLondonUK
  2. 2.MedPharm LtdGuildfordUK
  3. 3.School of PharmacyUniversity of HertfordshireHatfieldUK

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