title: In vitro transungual permeation of ciclopirox from a hydroxypropyl chitosan-based, water-soluble nail lacquer.
abstract: Commercial antimycotic nail lacquers are commonly based on water-insoluble resins. The present study was aimed at evaluating a novel, experimental nail lacquer (P-3051, Polichem SA, Lugano, Switzerland) based on the water-soluble film-forming agent hydroxypropyl chitosan (HPCH). The in vitro permeation of ciclopirox (CPX) from P-3051 and from a commercial, water-insoluble lacquer based on a vinyl resin (Penlac, Aventis Pharma), was investigated using thin membranes obtained from bovine hooves, an accepted model for human nails. Similar CPX permeation fluxes at steady state through the membranes, but significantly different lag times were observed for P-3051 and Penlac, when these were tested as dry films. The formulations thus appeared to influence only the time required by CPX to saturate the membrane, and not the final drug concentration gradient in the membrane. Permeation experiments performed on the same membranes and on hairless mouse skin with P-3051 and with a similar, HPCH-free vehicle (ERV), both tested in liquid form, disproved the possibility that HPCH might act as a permeation enhancer for CPX in either substrate. The possible reasons for the greater efficiency of the HPCH vehicle in terms of CPX transfer from the vehicle itself to the keratin membrane are discussed. This effect might be tentatively attributed to a particular affinity of HPCH for the membrane, resulting in intimate contact and strong adhesion of the HPCH lacquer to the keratin substrate.
authors.affiliation: Department of Bioorganic Chemistry and Biopharmaceutics, University of Pisa, Pisa, Italy. montid@farm.unipi.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.forename: L
authors.initials: L
authors.lastname: Saccomani
authors.forename: P
authors.initials: P
authors.lastname: Chetoni
authors.forename: S
authors.initials: S
authors.lastname: Burgalassi
authors.forename: M F
authors.initials: MF
authors.lastname: Saettone
authors.forename: F
authors.initials: F
authors.lastname: Mailland
mesh_terms: D000042:Absorption; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002417:Cattle; D048271:Chitosan; D002851:Chromatography, High Pressure Liquid; D000077768:Ciclopirox; D005079:Excipients; D006724:Hoof and Claw / Q000737:chemistry*; D066298:In Vitro Techniques; D007764:Lacquer; D008567:Membranes, Artificial; D051379:Mice; D014677:Pharmaceutical Vehicles; D011728:Pyridones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012044:Regression Analysis; D012995:Solubility
chemical_list: D000935:Antifungal Agents; D005079:Excipients; D008567:Membranes, Artificial; D014677:Pharmaceutical Vehicles; D011728:Pyridones; D000077768:Ciclopirox; D048271:Chitosan