title: A preformulation strategy for the selection of penetration enhancers for a transungual formulation.
abstract: Onychomycosis is associated with the cutaneous fungal infection of the nail and the nail folds (skin surrounding the nail). It is therefore important to target drug delivery into the nail folds along with nail plate and the nail bed. Systematic and strategic selection of the penetration enhancers specific for the skin and the nail is discussed. Twelve penetration enhancers were screened for their ability to improve solubility, in vitro nail penetration, in vitro skin permeation, and in vitro skin penetration of the antifungal drug ciclopirox olamine. In contrast to transdermal drug delivery, the main selection criteria for skin penetration enhancer in topical drug delivery were increased drug accumulation in the epidermis and minimal permeation across the skin. Thiourea improved the solubility and nail penetration of ciclopirox olamine. It also showed enhancement in the transungual diffusion of the drug. Propylene glycol showed a 12-fold increase in solubility and 3-fold increase in epidermal accumulation of ciclopirox olamine, while minimizing the transdermal movement of the drug. Thiourea was the selected nail permeation enhancer and propylene glycol was the selected skin penetration enhancer of ciclopirox olamine. A combination of the selected enhancers was also explored for its effect on drug delivery to the nail and nail folds. The enhancer combination reduced the penetration of ciclopirox in the skin and also the permeation through the nail. The proposed preformulation strategy helps to select appropriate enhancers for optimum topical delivery and paves way towards an efficient topical formulation for passive transungual drug delivery.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA 19140, USA.
authors.forename: Biji
authors.initials: B
authors.lastname: Palliyil
authors.forename: David B
authors.initials: DB
authors.lastname: Lebo
authors.forename: Pankil R
authors.initials: PR
authors.lastname: Patel
mesh_terms: D000287:Administration, Topical; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D000077768:Ciclopirox; D004058:Diffusion; D006801:Humans; D009262:Nails / Q000187:drug effects* / Q000378:metabolism; D010539:Permeability; D019946:Propylene Glycol / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011728:Pyridones / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D013890:Thiourea / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D011728:Pyridones; D000077768:Ciclopirox; D019946:Propylene Glycol; D013890:Thiourea