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

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.

Transungual Delivery, Anti-Inflammatory Activity, and In Vivo Assessment of a Cyclodextrin Polypseudorotaxanes Nail Lacquer

“…This establishes the suitability of HP-β-CD as a nail-friendly transungual permeation enhancer for poorly water-soluble drugs [21]. Additionally, the results are in accordance with those of Cutrin-Gomez et al, whose in vivo study optimized a ciclopirox olamine lacquer based on similar cyclodextrin polypseudorotaxanes that was applied to the nails of healthy volunteers for 45 days, leading to no negative effects on the nail surface [58]. A decrease in TOWL was observed after the application of REG and BET, but without significant differences.…”

Strategies for the enhancement of nail plate permeation of drugs to treat onychomycosis

“…More recently, Cutrín‐Gómez et al 51 developed a new formulation of the same 8% ciclopirox nail lacquer that showed enhanced permeation of the drug ex vivo.…”

“…P-3051 showed increased efficacy compared with the placebo and reference groups. 22 More recently, Cutrín-Gómez et al 51 developed a new formulation of the same 8% ciclopirox nail lacquer that showed enhanced permeation of the drug ex vivo.…”

Assessment of Physical, Mechanical, Biopharmaceutical Properties of Emulgels and Bigel Containing Ciclopirox Olamine

“…We selected the antifungal active substance ciclopirox olamine for this study. Ciclopirox olamine is a synthetic, broad-spectrum antifungal substance whose molecular weight is 268.35 Da, logP is 2.15, sparingly soluble in water (14.41 mg/mL), and ciclopirox pKa is 6.84 [ 26 ]. The minimum inhibitory concentration of ciclopirox olamine for most human pathogenic fungi is 0.5–3.9 µg/mL [ 27 ].…”