Article

In vitro human nail penetration and kinetics of panthenol

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Abstract

The in vitro absorption of panthenol into and through the human nail was examined in this study. Panthenol, the alcohol form of pantothenic acid (vitamin B5), is believed to act as a humectant and improve the flexibility and strength of nails. A liquid nail treatment formulated with panthenol (2%) was compared to a solution of panthenol (2%) in water. Fingernail specimens were dosed daily for 7 days with either the nail treatment (non-lacquer film forming) formulation or aqueous solution with sampling performed every 24 h. Panthenol concentrations were determined in the dorsal surface, interior (by drilling and removal) and in the supporting bed under the human nail. Panthenol levels in the dorsal nail (R(2) = 0.87; P < 0.001), nail interior (R(2) = 0.94; P < 0.001) and nail supporting bed (R(2) = 0.79; P < 0.003) showed a significant linear increase with each day of dosing. Significantly more panthenol was delivered into the interior nail and supporting bed by a nail treatment formulation than from an aqueous solution. The film acts not only as a reservoir of panthenol, but also acts to increase the hydration of the nail and the thermodynamic activity of panthenol as well, thereby enhancing diffusion.

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This study determines the enhancing effects of 2-n-nonyl-1,3-dioxolane on the penetration of econazole, an antifungal drug, into the deeper layers of the human nail where fungal infection resides. Aliquots (10 microL) of Econail lacquer formulation containing 0.45 mg of [(14)C]-econazole with 18% 2-n-nonyl-1,3-dioxolane (test group) or without 2-n-nonyl-1,3-dioxolane (control group) were applied twice daily for 14 days to human nails that had been washed with ethanol before each morning's application. The hydration of the nail sample was well controlled to simulate normal physiological conditions. After 14 days of dosing, the inner ventral section of the nail plate was assayed for absorbed drug content, using a micrometer-controlled drilling and nail powder removal system. The mass balance values of [(14)C]-econazole in this study were 90.8 and 96.4% for the test and control groups, respectively. The weight-normalized econazole content in the ventral/intermediate nail plate center in the test group was 6-fold greater than that in the control (p = 0.008). The total econazole absorbed into the supporting bed cotton ball in the test group was nearly 200-fold greater than that in the control group (p = 0.008) over the 14-day period. The amount of econazole after dosing in the inner part of the human nail (potential diseased area) was 11.1 +/- 2.6 (SD) microg/mg of nail powder with 2-n-nonyl-1,3-dioxolane in the lacquer and 1.78 +/- 0.32 microg/mg without 2-n-nonyl-1,3-dioxolane (p = 0.008). The surface nail contained more econazole (p = 0.004), that is, nonabsorbed drug, where 2-n-nonyl-1,3-dioxolane was not part of the dosing solution. Econazole in the support bed under the nail (the total absorbed dose) was 47.5 +/- 22.0 mg in the lacquer with 2-n-nonyl-1,3-dioxolane and 0.2 +/- 0.1 mg in the lacquer without 2-n-nonyl-1,3-dioxolane (p = 0.008). Moreover the concentration in the deep nail layer in the test group is 14,000 times higher than minimum inhibitory concentration (MIC) believed necessary to inhibit the growth of infecting fungi (Dermatophytes species). In a subsequent study, [(14)C]-dioxolane did not penetrate the nail well. Therefore, the mechanism of enhancement of econazole penetration is at the formulation/nail interface.
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The human nail penetration of the antifungal ciclopirox was determined for marketed gel containing 0.77% of ciclopirox, an experimental gel containing 2% of ciclopirox, and a marketed lacquer containing 8% of ciclopirox. After 14 days dosing, unabsorbed drug remaining on the surface, drug within the infection-prone area, and the amount that had penetrated through the nail were determined. Ciclopirox delivery into and through the nail was significantly greater from the marketed gel, than from either the experimental gel or the nail lacquer (p < 0.05). In addition, the surface nail contained more unabsorbed drug from the lacquer. Further, the drug penetrating into and through the nail was also greater from the marketed gel, leading to a higher Calculated Efficacy Coefficient for the marketed gel, than from the marketed lacquer or the experimental gel. The formulation plays an important role in the enhancement of ciclopirox permeation into and through the human nail plate, and the concentration of ciclopirox in the formulation was not a factor in determining penetration.
Nail penetration: enhancement of topical delivery of antifungal drugs by chemical modification of the human nail
  • X Hui
  • R C Wester
  • S Barbadillo
  • H I Maibach
Hui, X., Wester, R.C., Barbadillo, S. and Maibach, H.I. Nail penetration: enhancement of topical delivery of antifungal drugs by chemical modification of the human nail. In: Textbook of Cosmetic Dermatology (Baran, R. and Maibach, H.I., eds), pp. 57–64. Taylor & Francis, London and New York (2005).