Hydrosoluble medicated nail lacquers: in vitro drug permeation and corresponding antimycotic activity.
BACKGROUND
Two nail lacquers, containing ciclopirox (CPX) or amorolfine (MRF), based on water-insoluble polymers are currently considered mainstays of topical treatment of onychomycosis. The present study aimed at evaluating the antimycotic activity of a new water-soluble nail lacquer containing CPX (CPX/sol), easily removable by washing with water and applicable to periungual skin.


OBJECTIVE
To compare transungual permeation of CPX with that of MRF in the same hydroxypropyl chitosan-based nail lacquer (MRF/sol) and with a nonwater-soluble reference (Loceryl); Galderma International, La Défense, France), and to evaluate the antimycotic activity of CPX/sol and Loceryl against the most common fungal strains that cause onychomycosis. Methods In vitro drug permeation experiments with CPX/sol, MRF/sol and Loceryl were carried out through bovine hoof slices. Experimental permeates from CPX/sol and Loceryl underwent in vitro susceptibility testing against clinical isolates of dermatophytes, moulds and yeast. Results MRF transungual flux from MRF/sol lacquer was significantly higher when compared with Loceryl. CPX was able to permeate hoof membranes more easily compared with MRF. CPX and MRF concentrations in the subungual fluids collected after application of CPX/sol or Loceryl were sufficient to inhibit fungal growth, with the exception of Candida parapsilosis. Smaller amounts of fluid containing CPX were required for complete inhibition of fungal growth. Efficacy index values were significantly higher for CPX/sol. Conclusions Application of the CPX/sol nail lacquer allows rapid nail penetration of CPX, providing CPX levels sufficient to inhibit fungal growth for a prolonged period of time (30 h) after application of lacquer dose. CPX/sol nail lacquer appeared superior to the market reference Loceryl in terms of both vehicle (hydroxypropyl chitosan) and active ingredient (CPX) as witnessed by its higher efficacy on all nail pathogens.
Monti
D
D
Department of Pharmaceutical Sciences, University of Pisa, via Bonanno 33, I-56100 Pisa, Italy. montid@farm.unipi.it
Saccomani
L
L
Chetoni
P
P
Burgalassi
S
S
Senesi
S
S
Ghelardi
E
E
Mailland
F
F
D000042:Absorption; D000287:Administration, Topical; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002417:Cattle; D000077768:Ciclopirox; D006724:Hoof and Claw; D006801:Humans; D007764:Lacquer; D009025:Morpholines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009262:Nails; D014009:Onychomycosis / Q000188:drug therapy* / Q000378:metabolism; D010539:Permeability; D019999:Pharmaceutical Solutions / Q000008:administration & dosage; D014677:Pharmaceutical Vehicles; D011728:Pyridones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012044:Regression Analysis; D012995:Solubility
D000935:Antifungal Agents; D009025:Morpholines; D019999:Pharmaceutical Solutions; D014677:Pharmaceutical Vehicles; D011728:Pyridones; D000077768:Ciclopirox; C038974:amorolfine