Enhanced human nail drug delivery: nail inner drug content assayed by new unique method.

The purpose of this study was to develop an assay method of the human inner nail plate and to compare nail drug penetration by a penetrating enhancing formulation (the test carrier formulation). The test carrier and saline formulations were tested using radiolabeled urea, ketoconazole, and salicylic acid. After twice dosing daily for 7 days on human nail plates, the under inner section of the nail plate was assayed for absorbed drug content using a unique drilling/removal system. Results show that the weight-normalized radioactivity contents of three chemicals in the inner intermediate nail plate center in the carrier formulation were two fold higher than those from saline (p < 0.05). Total radioactivity recovery of dosed [(14)C]-salicylic acid was 89 +/- 2% in the carrier formulation and 88 +/- 5% in saline. In saline formulation, salicylic acid showed greater binding to the outer nail, making it less bioavailable for the inner nail area. This didn't occur with carrier formulation. In conclusion, topical treatment of nail diseases such as onychomycosis is not yet sufficiently effective, likely because of minimal drug penetration into the inner nail plate where the disease perpetuates. The assay system has the unique characteristic of being able to assay the inner part of the nail where the disease resides.

[1]  Howard I. Maibach,et al.  In Vivo Bioavailability and Metabolism of Topical Diclofenac Lotion in Human Volunteers , 1998, Pharmaceutical Research.

[2]  H. Maibach,et al.  In Vitro Cutaneous Disposition of a Topical Diclofenac Lotion in Human Skin: Effect of a Multi-Dose Regimen , 1998, Pharmaceutical Research.

[3]  K. Sugibayashi,et al.  Drug Permeation through the Three Layers of the Human Nail Plate , 1999, The Journal of pharmacy and pharmacology.

[4]  B. Elewski,et al.  Prevalence of onychomycosis in patients attending a dermatology clinic in northeastern Ohio for other conditions. , 1997, Archives of dermatology.

[5]  B. Lippold,et al.  In‐vitro Permeability of the Human Nail and of a Keratin Membrane from Bovine Hooves: Prediction of the Penetration Rate of Antimycotics through the Nail Plate and their Efficacy , 1997, The Journal of pharmacy and pharmacology.

[6]  B. Lippold,et al.  In‐vitro Permeability of the Human Nail and of a Keratin Membrane from Bovine Hooves: Influence of the Partition Coefficient Octanol/Water and the Water Solubility of Drugs on their Permeability and Maximum Flux , 1997, The Journal of pharmacy and pharmacology.

[7]  T. Franz Absorption of amorolfine through human nail. , 1992, Dermatology.

[8]  C. Meisel The Treatment of Onychomycosis in Clinical Practice , 1990 .

[9]  G. Flynn,et al.  Physicochemical characterization of the human nail: solvent effects on the permeation of homologous alcohols * , 1985, The Journal of pharmacy and pharmacology.

[10]  G. Flynn,et al.  Permeability characteristics of the human nail plate , 1983, International journal of cosmetic science.

[11]  G. Stüttgen,et al.  Bioavailability, Skin‐and Nailpenetration of Topically Applied Antimycotics * , 1982, Mykosen.

[12]  G. Flynn,et al.  Physicochemical characterization of the human nail: I. Pressure sealed apparatus for measuring nail plate permeabilities. , 1981, The Journal of investigative dermatology.

[13]  C. Orfanos,et al.  The human nail: structure, growth and pathological changes. , 1981, Current problems in dermatology.