title: In vitro permeation and penetration of ciclopirox olamine from poloxamer 407-based formulations--comparison of isolated human stratum corneum, bovine hoof plates and keratin films.
abstract: Fungal infections of skin and/or nails are common diseases resulting in major challenges in topical treatment. Therefore, the objective of the present study was to develop a dermal formulation targeting both tinea pedis and onychomycosis. The antifungal agent ciclopirox olamine (CPX) was incorporated into a variety of poloxamer 407-based formulations and analysed regarding its in vitro permeation and penetration behaviour across keratin films (KF) and bovine hoof plates as artificial nail models as well as human stratum corneum (SC). The novel compositions consisted of poloxamer 407 (P407), double distilled water, propylene glycol, isopropyl alcohol and medium chain triglycerides in given ratios. All the formulations exhibited semi-solid to liquid consistencies and were isotropic under a polarising microscope. Upon CPX incorporation, the formulations became softer and the yield stresses decreased. Increasing temperature led to higher complex viscosities. Permeation coefficients (P) from P407-based formulations across KF and bovine hoof plates and normalised retained CPX amounts in KF and bovine hoof plates were higher in comparison to the nail lacquer Ciclopoli(®) as a marketed reference. Data of KF and bovine hoof plates were comparable, therefore KF are suggested as artificial nail model for in vitro permeation studies besides the well-accepted nail model of bovine hoof plates. With regard to SC permeation, several liquid formulations indicated higher P in comparison to the references Ciclopoli(®) and the antimycotic skin formulation Selergo(®) 1% cream, while the normalised retained API amounts in SC were higher in comparison with Selergo(®) 1% cream or in the same range as Ciclopoli(®).
authors.affiliation: Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Mendelssohnstraße 1, 38106 Braunschweig, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Täuber
authors.affiliation: Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Mendelssohnstraße 1, 38106 Braunschweig, Germany. Electronic address: c.mueller-goymann@tu-braunschweig.de.
authors.forename: Christel C
authors.initials: CC
authors.lastname: Müller-Goymann
mesh_terms: D000328:Adult; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry; D002417:Cattle; D002626:Chemistry, Pharmaceutical; D000077768:Ciclopirox; D005260:Female; D006724:Hoof and Claw / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007633:Keratins / Q000378:metabolism*; D008875:Middle Aged; D020442:Poloxamer / Q000008:administration & dosage* / Q000737:chemistry; D011728:Pyridones / Q000008:administration & dosage* / Q000737:chemistry; D012212:Rheology; D012867:Skin / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D011728:Pyridones; D020442:Poloxamer; D000077768:Ciclopirox; D007633:Keratins
keywords: Ciclopirox olamine; Keratin film; Onychomycosis; Poloxamer 407: permeation; Tinea pedis