title: UV-curable gel formulations: Potential drug carriers for the topical treatment of nail diseases.
abstract: Nail diseases are common, cause significant distress and treatments are far from successful. Our aim was to investigate the potential of UV-curable gels - currently used as cosmetics - as topical drug carriers for their treatment. These formulations have a long residence on the nail, which is expected to increase patient compliance and the success of topical therapy. The gels are composed of the diurethane dimethacrylate, ethyl methacrylate, 2-hydroxy-2-methylpropiophenone, an antifungal drug (amorolfine HCl or terbinafine HCl) and an organic liquid (ethanol or NMP) as drug solvent. Following its application to a substrate and exposure to a UVA lamp for 2 min, the gel polymerises and forms a smooth, glossy and amorphous film, with negligible levels of residual monomers. No drug-polymer interactions were found and drug loading did not affect the film's properties, such as thickness, crystallinity and transition temperatures. In contrast, the organic solvent did influence the film's properties; NMP-containing films had lower glass transition temperatures, adhesion and water resistance than ethanol-based ones. Water-resistance being a desired property, ethanol-based formulations were investigated further for stability, drug release and ungual permeation. The films were stable under accelerated stability testing conditions. Compared to terbinafine, amorolfine was released to a greater extent, had a higher ungual flux, but a lower concentration in the nailplate. However, both drugs were present at considerably high levels in the nail when their MICs are taken into account. We thus conclude that UV-curable gels are promising candidates as topical nail medicines.
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, UK.
authors.forename: Laxmi Valji
authors.initials: LV
authors.lastname: Kerai
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hilton
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, UK. Electronic address: s.murdan@ucl.ac.uk.
authors.forename: Sudaxshina
authors.initials: S
authors.lastname: Murdan
mesh_terms: D000287:Administration, Topical; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects*; D065546:Drug Liberation; D000431:Ethanol / Q000737:chemistry; D005782:Gels; D006801:Humans; D008689:Methacrylates / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects; D008768:Methylmethacrylates / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects; D009025:Morpholines / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects; D009260:Nail Diseases / Q000188:drug therapy; D009262:Nails / Q000378:metabolism; D009281:Naphthalenes / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects; D011427:Propiophenones / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects; D011760:Pyrrolidinones / Q000737:chemistry; D000077291:Terbinafine; D014466:Ultraviolet Rays; D014520:Urethane / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000528:radiation effects
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D005782:Gels; D008689:Methacrylates; D008768:Methylmethacrylates; D009025:Morpholines; D009281:Naphthalenes; D011427:Propiophenones; D011760:Pyrrolidinones; C528099:diurethane dimethacrylate; D014520:Urethane; D000431:Ethanol; C009931:poly(ethylmethacrylate); C038974:amorolfine; D000077291:Terbinafine; C038678:N-methylpyrrolidone; C492094:2-hydroxy-2-methylpropiophenone
keywords: Acrylates; Onychomycosis; Permeation; Release; UV gel; Ungual