Optimization of Drug Permeation from 8% Ciclopirox Cyclodextrin/Poloxamer-Soluble Polypseudorotaxane-Based Nail Lacquers

Elena Cutrín-Gómez,Andrea Conde-Penedo,José Luis Gómez-Amoza,Francisco J Otero-Espinar,Soledad Anguiano-Igea

doi:10.3390/pharmaceutics12030231

Elena Cutrín-Gómez, Andrea Conde-Penedo + Show 3 more

Open Access

https://doi.org/10.3390/pharmaceutics12030231

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Journal: Pharmaceutics	Publication Date: Mar 5, 2020
Citations: 7	License type: CC BY 4.0

Affiliation: University of Santiago de Compostela

Abstract

Cyclodextrin/poloxamer-soluble polypseudorotaxane-based nail lacquers have demonstrated significant capacity for promoting the permeation of drugs into the nail plate. Furthermore, previous studies have shown that the use of hydroalcoholic blends as vehicles promotes drug permeation. The work described herein studies the effect of the type of alcohol used in the lacquer preparation, and the composition of the vehicle is optimized to obtain soluble doses of 8% and to promote the diffusion of ciclopirox base and olamine across the nail. Permeation studies on different types of alcohols show that optimum results are achieved with short-chain alcohols, and that results become less satisfactory the higher the number of alcohol carbons. In addition, solubility and penetration studies on the bovine hoof have enabled the composition of the lacquer to be optimized for both forms of ciclopirox. The results suggest that optimized lacquers have better ciclopirox diffusion and penetration properties than the commercial reference lacquer. Lastly, in vivo studies in which optimized ciclopirox olamine lacquer was applied for 45 days to the nails of healthy volunteers showed that it caused no negative effects or changes to the nail surface. These results demonstrate the significant potential of cyclodextrin/poloxamer-soluble polypseudorotaxane-based nail lacquers for the ungual administration of drugs.

Highlights

Onychomycosis is a fungal infection of the nail caused by dermatophytes, nondermatophyte molds, and yeast that can affect 2–18.5%, or higher, of the world’s population [1]
The bovine hoof model has been used in different works in permeation studies as an alternative to human nail
Microstructural characterization of bovine hoof and human nail has shown that the bovine hoof surface is more porous than the nail surface, the internal porosity is similar for both substrates [10]

Summary

Introduction

Onychomycosis is a fungal infection of the nail caused by dermatophytes, nondermatophyte molds, and yeast that can affect 2–18.5%, or higher, of the world’s population [1]. Of the drug used, the composition of most of the lacquers sold is based on the use of hydrophobic polymers dispersed or dissolved in volatile organic solvents, designed to promote the formation of even, impermeable films on the nail surface. Examples are Penlac® nail lacquer (Aventis Pharma, Frankfurt am Main, Germany) and Ciclochem 8%, which contain the drug (80 mg ciclopirox; 8%) dissolved in a blend of ethyl acetate and isopropyl alcohol and butyl monoester of poly(methylvinyl ether/maleic acid) as the film-forming polymer. The formation of an impermeable hydrophobic film prevents nail transpiration, which encourages fungal growth These types of lacquer require removal between applications using organic solvents or nail files, which causes damage and irritation to the nail and surrounding skin area [7]

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