Loceryl nail lacquer--realization of a new galenical approach to onychomycosis therapy.
Loceryl nail lacquer was developed to provide the effective antifungal drug, amorolfine, in a once-weekly dosage regimen combined with a convenient mode of application. Traditional formulations such as creams and nail solutions do not fulfil these requirements because they are wiped or washed off very rapidly. Amorolfine nail lacquer builds a non-water-soluble film on the nail plate, and this film remains in place for 1 week. The film contains a high concentration of amorolfine and forms a depot from which the drug is delivered and which allows the drug to permeate the nail plate. The film-forming polymer and the solvent were optimized for drug release, stability, and convenience of application (drying time, no gloss, transparency). In preclinical development, porcine hoof horn was used as a screening model to differentiate between formulations and dosage strengths with respect to the penetration rate. A high drug concentration of 11.72 micrograms/specimen (10 mm in diameter) was reached in the hoof horn after 6 h, increasing to 39.5 micrograms/specimen within 7 days, the maximum duration of the investigation. The drug concentration achieved was far above its minimum inhibitory concentration. Furthermore, the penetration model clearly indicated that amorolfine crossed the horn barrier and was found in the moistened gauze which simulated the nail bed. After a 7-day penetration period, 1.8% of the applied dose (500 micrograms) was available under the nail.
Pittrof
F
F
Pharma Division Preclinical Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Gerhards
J
J
Erni
W
W
Klecak
G
G
D000287:Administration, Topical; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D007764:Lacquer; D009025:Morpholines / Q000008:administration & dosage*; D009262:Nails / Q000737:chemistry; D014009:Onychomycosis / Q000188:drug therapy*; D012869:Skin Absorption
D000935:Antifungal Agents; D009025:Morpholines; C038974:amorolfine