PHARMACEUTICAL FORMULATIONS FOR IONTOPHORETIC DELIVERY OF AN ANTI-FUNGAL DRUG
Pharmaceutical formulations suitable for iontophoresis thereof that provide enhanced iontophoretic delivery of an anti-fungal drug to at least one body surface are described. Also described are pharmaceutical formulations suitable for iontophoresis comprising terbinafine and methods for administering terbinafine to a body surface via iontophoresis. In one embodiment, the body surface includes a nail plate and/or the skin.
1 . A formulation suitable for iontophoresis comprising terbinafine hydrochloride, one or more solvents or co-solvents and a permeation enhancer.
2 . The formulation of claim 1 wherein the terbinafine hydrochloride is present in an amount from about 1 to about 10% (w/w).
3 . The formulation of claim 2 wherein the one or more solvent or co-solvents are each present in an amount from about 10 to about 50% (w/w).
4 . The formulation of claim 3 wherein said formulation comprises water, an alcohol and glycerin.
5 . The formulation of claim 1 wherein the permeation enhancer is selected from the group consisting of benzoic acid, oleic acid, salicylic acid, cysteine hydrochloride, N-acetylcysteine and urea.
6 . The formulation of claim 1 wherein the permeation enhancer is present in an amount from about 0.05 to about 50% (w/w).
7 . The formulation of claim 5 wherein the permeation enhancer is benzoic acid.
8 . The formulation of claim 7 wherein the benzoic acid is present in an amount from about 0.05 to about 5% (w/w).
9 . The formulation of claim 8 wherein the benzoic acid is present in an amount of about 0.2% (w/w).
10 . The formulation of claim 6 wherein the permeation enhancer is polyvinylpyrrolidone.
11 . The formulation of claim 6 , wherein the permeation enhancer is a polyethylene glycol.
12 . The formulation of claim 11 , wherein the polyethylene glycol is polyethylene glycol 400.
13 . The formulation of claim 1 further comprising an antioxidant.
14 . The formulation of claim 13 wherein the antioxidant is butylated hydroxytoluene (BHT).
15 . The formulation of claim 1 further comprising a chelating agent.
16 . The formulation of claim 15 wherein the chelating agent is disodium EDTA.
17 . The formulation of claim 1 further comprising a viscosity modifying agent.
18 . The formulation of claim 17 wherein the viscosity modifying agent is hydroxyethylcellulose (HEC).
19 . The formulation of claim 1 further comprising a non-ionic surfactant.
20 . The formulation of claim 19 wherein the non-ionic surfactant is selected from the group consisting of polysorbate-20, polysorbate-40 and polysorbate-80.
21 . The formulation of claim 15 wherein the chelating agent is present in an amount from about 0.01 to about 0.10% (w/w).
22 . The formulation of claim 13 wherein the antioxidant is present in amount from about 0.005 to about 0.10% (w/w).
23 . The formulation of claim 17 wherein the viscosity modulating agent is present in an amount from about 0.10 to about 0.50% (w/w).
24 . The formulation of claim 19 wherein the non-ionic surfactant is present in an amount from about 1 to about 10% (w/w).
25 . The formulation of claim 1 wherein the pH of the formulation is about 2.5 to about 4.5.
26 . The formulation of claim 1 comprising terbinafine hydrochloride, ethanol, glycerin and benzoic acid.
27 . The formulation of claim 26 comprising about 4% (w/w) terbinafine hydrochloride, about 0.2% (w/w) benzoic acid, about 21% (w/w) ethanol and about 40% (w/w) glycerin.
28 . The formulation of claim 27 further comprising a polysorbate in an amount of about 5% (w/w), wherein the polysorbate is polysorbate-80.
29 . The formulation of claim 28 further comprising about 0.01% (w/w) butylated hydroxytoluene (BHT), about 0.01% (w/w) disodium EDTA, about 5% (w/w) polysorbate-80 and about 0.3% HEC.
30 . A method of administering terbinafine to a patient in need thereof comprising iontophoretically administering to a body surface of said patient the formulation of claim 1 .
31 . The method of claim 30 , wherein the terbinafine is terbinafine hydrochloride.
32 . The method of claim 31 , wherein a current density of at least about 10 μA/cm 2 is applied.
33 . The method of claim 31 wherein a current dose from about 0.5 mA*min to about 25 mA*min is administered.
34 . A method for the treatment of a fungal infection in a patient suffering therefrom comprising iontophoretically administering the formulation of claim 1 to a body surface of said patient.
35 . The method of claim 34 wherein the fungal infection affects the patient's scalp, body, groin, feet, fingernails or toenails.
36 . The method of claim 35 , wherein the fungal infection is a dermatophyte infection of the nail.
37 . The method of claim 36 , wherein the dermatophyte infection is onychomycosis.
38 . The method of claim 34 wherein the fungal infection is tinea capitis.
39 . The method of claim 38 wherein the formulation is administered to the nail plate or to the nail plate and surrounding tissue.
40 . A method for the treatment of a fungal infection in a patient suffering therefrom comprising iontophoretically administering an anti-fungal agent to a body surface of said patient.
41 . The method of claim 40 wherein the antifungal drug is selected from the group consisting of ketoconazole, econazole, ciclopirox, ciclopirox olamine, terbinafine, fluconazole, itraconazole and amorolfine.