TOPICAL ACYCLOVIR FORMULATIONS AND USES THEREOF
Provided herein are gel formulations of acyclovir with a low concentration of acyclovir, which can be used, for example, for the treatment of recurrent herpes labialis (cold sores) in immunocompetent adults and adolescents 12 years of age and older. The gel formulation can be an aqueous gel formulation, an emulsified gel formulation, or a non-aqueous gel formulation.
1 . An aqueous gel formulation comprising acyclovir dissolved or partially suspended in an aqueous gel,
wherein the acyclovir is in an amount of about 0.05% to about 0.5% by weight of the aqueous gel formulation,
wherein the aqueous gel comprises a solvent system and an effective amount of a gel-forming agent,
wherein the solvent system comprises water in an amount of about 20% to about 80% by weight of the aqueous gel formulation; and one or more water-miscible organic solvents in an amount of about 15% to about 70% by weight of the aqueous gel formulation; and
wherein the aqueous gel formulation is formulated for topical use.
2 . The aqueous gel formulation of claim 1 , wherein the one or more water-miscible organic solvents are selected from propylene glycol, glycerol, diethylene glycol monoethyl ether, dimethyl sulfoxide, a low molecular weight polyethylene glycol, and combinations thereof.
3 . The aqueous gel formulation of claim 1 , wherein the one or more water-miscible organic solvents comprise diethylene glycol monoethyl ether in an amount of about 10% to about 60% by weight.
4 . The aqueous gel formulation of claim 1 , wherein the one or more water-miscible organic solvents comprise a low molecular weight polyethylene glycol in an amount of about 5% to about 40% by weight.
5 . The aqueous gel formulation of claim 4 , wherein the low molecular weight polyethylene glycol is polyethylene glycol 400.
6 . An emulsified gel formulation comprising acyclovir dissolved or partially suspended in an emulsified gel,
wherein the acyclovir is in an amount of about 0.05% to about 0.5% by weight of the emulsified gel formulation,
wherein the emulsified gel comprises a solvent system, an oil, an emulsifier and an effective amount of a gel-forming agent,
wherein the solvent system comprises water in an amount of about 20% to about 80% by weight of the emulsified gel formulation; and one or more water-miscible organic solvents in an amount of about 15% to about 70% by weight of the emulsified gel formulation; and
wherein the emulsified gel formulation is formulated for topical use.
7 . The emulsified gel formulation of claim 6 , wherein the one or more water-miscible organic solvents are selected from propylene glycol, glycerol, diethylene glycol monoethyl ether, dimethyl sulfoxide, a low molecular weight polyethylene glycol, and combinations thereof.
8 . The emulsified gel formulation of claim 6 , wherein the one or more water-miscible organic solvents comprise diethylene glycol monoethyl ether in an amount of about 10% to about 60% by weight.
9 . The emulsified gel formulation of claim 6 , wherein the one or more water-miscible organic solvents comprise a low molecular weight polyethylene glycol in an amount of about 5% to about 40% by weight.
10 . The emulsified gel formulation of claim 7 , wherein the low molecular weight polyethylene glycol is polyethylene glycol 400.
11 . The emulsified gel formulation of claim 6 , wherein the oil is a triglyceride of caprylic and/or capric acid or a mixed ester of palm oil or coconut oil in an amount of about 1% to about 20% by weight of the emulsified gel formulation.
12 . The emulsified gel formulation of claim 6 , wherein the emulsifier comprises an acrylamide and sodium acryloyldimethyl taurate copolymer dispersed in isohexadecane and a non-ionic surfactant.
13 . A non-aqueous gel formulation comprising acyclovir dissolved or partially suspended in a non-aqueous gel,
wherein the acyclovir is in an amount of about 0.05% to about 0.5% by weight of the non-aqueous gel formulation,
wherein the non-aqueous gel comprises a solvent system and an effective amount of a gel-forming agent,
wherein the solvent system comprises one or more solvents selected from propylene glycol, glycerol, diethylene glycol monoethyl ether, dimethyl sulfoxide, a low molecular weight polyethylene glycol, and combinations thereof; and
wherein the non-aqueous gel formulation is formulated for topical use.
14 . An aqueous gel formulation comprising: a) acyclovir in an amount of about 0.05% to about 0.5% by weight of the aqueous gel formulation; b) water; c) diethylene glycol monoethyl ether; and d) a gel-forming agent.
15 . The aqueous gel formulation of claim 14 , further comprising a low molecular weight polyethylene glycol with an average molecular weight less than 700.
16 . The aqueous gel formulation of claim 15 , wherein the low molecular weight polyethylene glycol is PEG 400.
17 . The aqueous gel formulation of claim 15 , wherein the weight ratio of diethylene glycol monoethyl ether to the low molecular weight polyethylene glycol ranges from about 20:1 to about 1:5.
18 . The aqueous gel formulation of claim 15 , wherein the weight ratio of diethylene glycol monoethyl ether to the low molecular weight polyethylene glycol ranges from about 10:1 to about 2:1.
19 . The aqueous gel formulation of claim 14 , wherein the weight ratio of water to diethylene glycol monoethyl ether ranges from about 5:1 to about 1:5.
20 . The aqueous gel formulation of claim 14 , comprising by weight of the aqueous gel formulation, water in an amount of about 30-50%, diethylene glycol monoethyl ether in an amount of about 35-65%, and PEG 400 in an amount of about 5-15%.
21 . The aqueous gel formulation of claim 14 , wherein the gel-forming agent is a crosslinked polyacrylic acid.
22 . The aqueous gel formulation of claim 14 , wherein the pH of the aqueous gel formulation is about 4 to 8.
23 . The aqueous gel formulation of claim 14 , wherein acyclovir is the only active ingredient.
24 . The aqueous gel formulation of claim 14 , further comprising an antioxidant or preservative selected from butylated hydroxytoluene, phenoxyethanol, sodium metabisulfite, EDTA, ascorbic acid, and combinations thereof.
25 . The aqueous gel formulation of claim 14 , which is substantially free of acyclovir in a solid form.
26 . A method of treating or preventing herpes labialis in a subject in need thereof comprising topically applying to the subject an effective amount of the aqueous gel formulation of claim 14 .
27 . A method of treating or preventing herpes viral infections of the skin or mucosa of a subject in need thereof comprising topically applying to the subject an effective amount of the aqueous gel formulation of claim 14 .
28 . A method of treating or preventing herpes zoster infections of the skin or mucosa of a subject in need thereof comprising topically applying to the subject an effective amount of the aqueous gel formulation of claim 14 .
29 . A method of treating or preventing herpes varicella infections of the skin or mucosa of a subject in need thereof comprising topically applying to the subject an effective amount of the aqueous gel formulation of claim 14 .
30 . A method of treating or preventing one or more diseases selected from genital herpes simplex, neonatal herpes simplex, cold sores, shingles, acute chickenpox, acute mucocutaneous HSV infections, herpes of the eye, and herpes simplex blepharitis, the method comprising topically applying to a subject in need thereof an effective amount of the aqueous gel formulation of claim 14 .