Controlling the Bioavailability of Active Ingredients in Topical Formulations
Described are methods and compositions for tuning the bioavailability of an active agent, such as a corticosteroid, in a topical formulation.
1 . A method of optimizing the rate of release of an active agent from a topical formulation, comprising the step of varying the weight ratio of vegetable oil-to-mineral oil from about 0.0 to about 2.6, and varying the weight ratio of co-surfactant-to-surfactant from about 0.89 to about 2.0, thereby forming an improved active agent-containing topical formulation.
2 . The method of claim 1 , wherein the rate of release of the active agent from the improved active agent-containing topical formulation is greater over time than the rate of release of the active agent from a reference formulation.
3 . The method of claim 1 , wherein the weight ratio of vegetable oil-to-mineral oil in the improved active agent-containing formulation is about 0, about 0.03, about 0.06, about 0.13, about 0.2, about 0.55, about 0.75, about 1.0, about 1.25, about 1.50, about 1.75, about 2.0, about 2.25, or about 2.6; and the weight ratio of co-surfactant-to-surfactant in the improved active agent-containing formulation is about 0.89, about 1.0, about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, or about 2.0.
4 . The method of claim 1 , wherein the active agent is a corticosteroid.
5 . The method of claim 1 , wherein the active agent is hydrocortisone 17-butyrate.
6 . The method of claim 1 , wherein the improved active agent-containing topical formulation comprises vegetable oil; and the vegetable oil comprises poly-unsaturated fatty acids in an amount from about 10% to about 78% of the number of fatty acids.
7 . The method of claim 6 , wherein the poly-unsaturated fatty acid is linoleic acid.
8 . The method of claim 1 , wherein the improved active agent-containing topical formulation comprises vegetable oil; and the vegetable oil is safflower oil, sunflower oil, corn oil, sesame oil, peanut oil, canola oil, or olive oil.
9 . The method of claim 1 , wherein the improved active agent-containing topical formulation comprises vegetable oil; and the vegetable oil is safflower oil.
10 . The method of claim 1 , wherein the mineral oil is light mineral oil.
11 . The method of claim 1 , wherein the improved active agent-containing topical formulation is an oil-in-water emulsion.
12 . The method of claim 1 , wherein the improved active agent-containing topical formulation consists essentially of, by weight of the formulation
Hydrocortisone 17-butyrate
From about 0.01% to about 0.2%
Water
From about 20% to about 90%
Propylparaben
From about 0.05% to about 0.15%
Cetostearyl Alcohol
From about 2% to about 9%
White Petrolatum
From about 1.5% to about 60%
Ceteth-20
From about 1% to about 9%
Sodium Citrate
From about 0.07% to about 0.50%
Citric Acid
From about 0.09% to about 0.60%
Vegetable oil
From about 1% to about 9%
Mineral oil
From about 2% to about 27%
13 . The method of claim 1 , wherein the improved active agent-containing topical formulation consists essentially of, by weight of the formulation
Hydrocortisone 17-butyrate
From about 0.01% to about 0.2%
Water
From about 40% to about 70%
Glycerin
From about 2% to about 8%
Methylparaben
From about 0.1% to about 0.5%
Propylparaben
From about 0.05% to about 0.15%
Cetostearyl Alcohol
From about 2% to about 8%
Urea
From about 0.3% to about 0.9%
Dimethicone
From about 0.5% to about 1.5%
Vegetable oil
From about 3% to about 9%
White Petrolatum
From about 3% to about 9%
Mineral Oil
From about 6% to about 18%
Ceteth-20
From about 3% to about 9%
Butylated Hydroxytoluene
From about 0.015% to about 0.045%
Sodium Citrate
From about 0.015% to about 0.045%
Citric Acid
From about 0.2% to about 0.6%
14 . The method of claim 1 , wherein the improved active agent-containing topical formulation consists essentially of, by weight of the formulation,
Hydrocortisone 17-butyrate
From about 0.01% to about 0.2%
Water
From about 15% to about 45%
Butylparaben
From about 0.02% to about 0.08%
Propylparaben
From about 0.05% to about 0.15%
Cetostearyl Alcohol
From about 3% to about 9%
Vegetable Oil
From about 1.5% to about 4.5%
White Petrolatum
From about 20% to about 60%
Mineral Oil
From about 8% to about 22%
Ceteth-20
From about 1.5% to about 4.5%
Sodium Citrate
From about 0.06% to about 0.22%
Citric Acid
From about 0.09% to about 0.27%
15 . The method of claim 1 , wherein the improved active agent-containing topical formulation consists essentially of, by weight of the formulation
Hydrocortisone 17-butyrate
From about 0.01% to about 0.2%
Water
From about 45% to about 95%
Butylparaben
From about 0.02% to about 0.08%
Propylparaben
From about 0.05% to about 0.15%
Cetostearyl Alcohol
From about 2% to about 6%
vegetable Oil
From about 1.5% to about 4.5%
White Petrolatum
From about 1% to about 5%
Mineral Oil
From about 2% to about 8%
Ceteth-20
From about 1% to about 3%
Butylated Hydroxytoluene
From about 0.01% to about 0.03%
Sodium Citrate
From about 0.15% to about 0.45%
Citric Acid
From about 0.2% to about 0.6%
16 . A method of treating a skin disorder, comprising the steps of:
applying topically to an area of skin of a subject in need thereof a therapeutically-effective amount of an improved active agent-containing topical formulation of claim 1 .
17 . The method of claim 16 , wherein the formulation is applied once daily or twice daily.
18 . The method of claim 16 , wherein the subject is human.
19 . The method of claim 16 , wherein the skin disorder is a dermatosis.
20 . The method of claim 16 , wherein the skin disorder is atopic dermatitis.