Transungual delivery of ketoconazole using novel lacquer formulation

Dermatology Department-University of California, San Francisco 90 Medical Center Way, Surge Bldg. Room 110 San Francisco, CA 94143-0989. Electronic address: .
International Journal of Pharmaceutics (Impact Factor: 3.79). 09/2013; 456(2). DOI: 10.1016/j.ijpharm.2013.08.082
Source: PubMed

ABSTRACT Onychomycosis, a common fungal infection of the nail, can have a substantial impact on quality of life. The success of topical therapy for onychomycosis depends on effective penetration, which can be enhanced using an appropriate delivery method. This study evaluated the effectiveness of a novel topical lacquer on enhancing [14C]-ketoconazole penetration by comparing nail absorption, nail distribution, and nail penetration of [(14)C]-ketoconazole dissolved in the novel lacquer versus a commercial ketoconazole cream. Using the in vitro finite dose model, the formulations were applied daily to human nail plates for 7 days. Drug absorption was measured by monitoring rate of appearance in each nail layer and the supporting bed. After the multiple day treatment, cumulative concentrations of ketoconazole formulated in novel lacquer in the deep nail layer and the nail bed were significantly greater than cumulative concentrations of commercial ketoconazole (p<0.05), as well as several orders of magnitude greater than the Minimal Inhibitory Concentration (MIC) deemed necessary to inhibit the growth of causative dermatophytic and yeast species. These results suggest that this novel ketoconazole lacquer has the potential to be an effective topical treatment for onychomycosis.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although considered as trifling illness, nail diseases have a reasonably high occurrence and a noteworthy impact on the patients’ quality of life. Furthermore, there is a need to improve the topical treatment for nail diseases to avoid drug interactions and to reduce side effects associated with oral therapy. Topical drug delivery to the nails has established amplified consideration lately. Strategies (such as chemical enhancers, formulation strategies, physical and mechanical methods) are being investigated in order to improve drug permeability across the nail plate. The rationale of this review is to present contemporary information on the structure of human nail along with its comparison with animal hooves. Precincts of nail permeability have been briefly discussed with respect to factors like permeant's molecular size, hydrophilicity, charge and the nature of the vehicle etc. These factors affect drug uptake and permeation through the nail. Formulations like nail lacquers which mimic cosmetic varnish and colloidal carriers along with nail substitutes that can be utilized for TU delivery have also been discussed.This article is protected by copyright. All rights reserved.
    International journal of cosmetic science 05/2014; 36(5). DOI:10.1111/ics.12142 · 1.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The project was aimed at development of isotretinoin nail lacquer and assessment of its penetration efficiency across human nail plate. Preliminary studies (hydration enhancement factor and SEM) aided the selection of thioglycolic acid as permeation and eugenol was selected as local anesthetic in the formulation. The nail lacquer was optimized by 32 factorial design and a total of nine formulations were prepared and screened. In vitro adhesion and ex vivo permeation (cumulative drug permeation per unit area (CDP/A) = 6.61 ± 0.57 mg/cm2) across bovine hoof guided the selection of F3 as optimized formulation that was improvised. Viscosity adjustments to improve handling characteristics were affected by incorporation of ethyl cellulose (6%; F3M1) that scaled the viscosity to 312.681 cp and insignificantly (p > 0.05) affected CDP/A (6.32 ± 0.45 mg/cm2). In comparison to marketed preparation (Retino-A cream) F3M1 afforded two fold increase in CDP/A. The permeation characteristics were defined by Higuchi model (r2 = 0.964) and flux value of 176 μg/cm2/h. Confocal laser scanning microscopy, after 72 h of nail lacquer application, revealed extensive distribution of the fluorescent tracer across the human nail plate in comparison to control that was confined to the top layer. Conclusively, an efficacious and stable nail lacquer of isotretinoin was developed for potential clinical topical use to target the drug to nail bed in treatment of nail psoriasis.
    International Journal of Pharmaceutics 11/2014; DOI:10.1016/j.ijpharm.2014.11.050 · 3.79 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The present therapy adopted by physicians for the treatment of fungal includes the systemic administration and topical administration of antifungal agents. A concern in these formulations involves systemic adverse effects and also less concentration of drug at the site of infection. Hence an attention has recently been focused on novel drug delivery of antifungal agents which is the most widely accepted approach.
    Journal of Pharmaceutical Innovation 05/2014; · 1.25 Impact Factor