In vitro model of infected stratum corneum for the efficacy evaluation of poloxamer 407-based formulations of ciclopirox olamine against Trichophyton rubrum as well as differential scanning calorimetry and stability studies.
Superficial fungal skin infections are a common disease and concern 20-25% of the world's population with the dermatophyte Trichophyton rubrum being the main trigger. Due to autoinoculation, fungal skin infections of the feet (tinea pedis) often occur simultaneously with fungal nail infections (onychomycosis). Therefore, the overall objective was the development and characterisation of poloxamer 407-based formulations with the antimycotic active ingredient ciclopirox olamine (CPX) for simultaneous antifungal therapy. The formulations consisted of poloxamer 407, water, isopropyl alcohol, propylene glycol and medium chain triglycerides in given ratios. The in vitro antifungal efficacy against T. rubrum was tested in a novel in vitro model of infected stratum corneum in comparison to a marketed semi-solid formulation containing 1% (w/w) ciclopirox olamine and a marketed nail lacquer containing 8% ciclopirox. Several liquid poloxamer 407-based formulations with only 1% CPX completely inhibited fungal growth after 6 days of incubation, whereas the marketed semi-solid formulation did not inhibit fungal growth. Differential scanning calorimetry studies revealing the interaction between the formulations and the SC showed that increasing isopropyl alcohol/propylene glycol concentrations as well as increasing CPX concentrations caused increasing endothermic transition shifts. Moreover, stability studies at 30 °C exhibited only a slight decrease of the CPX amount after 12 months of storage. Each formulation contained >90% of the initial CPX concentration after termination of the stability studies.
Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Mendelssohnstraße 1, 38106 Braunschweig, Germany.
Anja
A
Täuber
Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Mendelssohnstraße 1, 38106 Braunschweig, Germany. Electronic address: C.Mueller-Goymann@tu-braunschweig.de.
Christel C
CC
Müller-Goymann
D000287:Administration, Topical; D000935:Antifungal Agents / Q000737:chemistry / Q000627:therapeutic use; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D000077768:Ciclopirox; D004355:Drug Stability; D004817:Epidermis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D020442:Poloxamer / Q000737:chemistry*; D011728:Pyridones / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D014249:Trichophyton / Q000187:drug effects*
D000935:Antifungal Agents; D011728:Pyridones; D020442:Poloxamer; D000077768:Ciclopirox
Ciclopirox olamine; Differential scanning calorimetry; Poloxamer 407; Tinea pedis; Trichophyton rubrum