Topical tetracycline compositions
View Patent ↗A topical therapeutic hydrophobic breakable composition includes a carrier comprising (a) about 60% to about 99% by weight of at least one hydrophobic oil; (b) at least one viscosity-modifying agents selected from the group consisting of a fatty alcohol, a fatty acid and a wax; and (c) a tetracycline antibiotic, characterized in that at least part of the tetracycline antibiotic is suspended in the composition; the viscosity of the composition is at least about 30% higher than the viscosity of the carrier without the tetracycline antibiotic; and is higher than the viscosity of the hydrophobic oil and the tetracycline antibiotic without the viscosity modifying agents; and the amount of viscosity modifying agents can optionally be reduced by at least an amount by weight that would have increased the viscosity of the carrier without the tetracycline antibiotic by at least 30%; wherein the tetracycline is chemically stable in the composition for at least six months; wherein more than about 90% of the tetracycline has not broken down; wherein when packaged in an aerosol container to which is added a liquefied or compressed gas propellant the composition affords upon release from the container a breakable foam of at least good quality that breaks easily upon application of shear force.
1. A method of treating acne vulgaris, comprising administering
a waterless foam composition comprising
a minocycline and a foamable carrier, the carrier comprising:
a) at least one hydrophobic oil; and
b) an agent comprising (i) at least one fatty alcohol and at least one wax; (ii) at least one fatty acid and at least one wax; (iii) at least one fatty alcohol, at least one fatty acid, and at least one wax; (iv) a wax comprising a hydrogenated oil; or (v) a combination of two or more waxes;
wherein the composition does not contain one or more minocycline incompatible substance selected from the group consisting of dimethyl sulfoxide (DMSO), dimethylformamide (DMF), acetonitrile, acetone, methyl ethyl ketone, 1,4-dioxane, tetrahydrofuran (THF), N-methylpyrrolidone, pyridine, piperidine, N-methyl-2-pyrrolidone and 1-methyl-2-pyrrolidinone), azone (1-dodecylazacycloheptan-2-one), dimethyl isosorbide, glycerin, ethanol, propylene glycol, butylene glycol, PEG 200, hexylene glycol, PEG 400, diethylene glycol monoethyl ether, pomegranate seed oil, isostearic acid, and ethocel;
wherein the composition does not contain a surfactant;
and wherein the composition does not contain a polyol.
2. The method of claim 1 , wherein the at least one hydrophobic oil comprises a mineral oil, a cocoglyceride, a silicone oil, a liquid paraffin, a caprylic/capric triglyceride, a coconut oil, a soybean oil, a cyclomethicone, disopropyl adipate isododecane, cetearyl octanoate, a gelled mineral oil, isopropyl myristate, PPG 15 stearyl ether, octyl dodecanol, a petrolatum, a calendula oil, a grape seed oil, an almond oil, a jojoba oil, an avocado oil, a peanut oil, a wheat germ oil, or a mixture of any two or more thereof.
3. The method of claim 1 , wherein at least one or both of the fatty alcohol or the fatty acid has at least 12 carbon atoms in its carbon backbone.
4. The method of claim 1 , wherein the agent comprises at least one fatty alcohol, at least one fatty acid, and at least one wax, wherein the at least one wax comprises a beeswax, a hydrogenated oil, or both.
5. The method of claim 1 , wherein the composition contains less than 0.4% by weight of a protic solvent, a polar aprotic solvent, and a silicone thickening agent.
6. The method of claim 1 , wherein the composition contains less than 0.4% by weight of a polymeric gelling agent, a short chain alcohol, and a silicone thickening agent.
7. The method of claim 1 , wherein the minocycline is minocycline hydrochloride.
8. The method of claim 1 , wherein the foamable carrier comprises:
a) 45% to 55% by weight of a soybean oil;
b) 21.2% to 26% by weight of a coconut oil;
c) 4.5% to 5.5% by weight of a cyclomethicone;
d) 0.85% to 4.8% by weight of a light mineral oil;
e) 3.2% to 3.9% by weight of cetostearyl alcohol;
f) 2.7% to 3.3% by weight of stearic acid;
g) 2.3% to 2.8% by weight of myristyl alcohol;
h) 1.8% to 2.2% by weight of hydrogenated castor oil;
i) 1.8% to 2.2% by weight of beeswax;
j) 1.4% to 1.7% by weight of stearyl alcohol; and
k) 1% to 1.2% by weight of behenyl alcohol.
9. The method of claim 1 , wherein the minocycline is present at about 1% to about 10% of the composition.
10. The method of claim 1 , wherein the minocycline is present at about 4% of the composition.
11. The method of claim 1 , further comprising an additional active agent.
12. The method of claim 1 , wherein the composition is free of or comprises less than 10% petrolatum by weight of the composition.
13. The method of claim 1 , wherein the at least one hydrophobic oil is about 60% to about 99% by weight of the composition.
14. The method of claim 1 , wherein the composition comprises less than 0.4% by weight of a polymeric gelling agent.
15. The method of claim 1 , wherein the composition is administered at least once daily.
16. The method of claim 1 , wherein the composition is administered at least once daily and the minocycline is present at about 4% of the composition.
17. The method of claim 1 , wherein the foam composition is produced with a liquefied or compressed gas propellant.
18. The method of claim 1 , comprising a hydrocarbon oil, an ester oil, an ester of a dicarboxylic acid, a triglyceride oil, an unsaturated or polyunsaturated oil, an essential oil, a canola oil, a castor oil, a corn oil, a cotton oil, a cottonseed oil, glycerol, an olive oil, a palm oil, a dimethicone, a fatty acid-modified silicone oil, or a mixture of any two or more thereof.
19. A method of treating acne vulgaris, comprising administering
a waterless composition comprising
a carrier and 1% to 10% by weight of the composition of a minocycline, wherein the carrier comprises:
a) at least one hydrophobic oil; and
b) an agent comprising (i) at least one fatty alcohol and at least one wax; (ii) at least one fatty acid and at least one wax; (iii) at least one fatty alcohol, at least one fatty acid, and at least one wax; (iv) a wax comprising a hydrogenated oil; or (v) a combination of two or more waxes;
wherein the composition does not contain a surfactant;
wherein the composition does not contain a polyol.
20. The method of claim 19 , wherein the minocycline is minocycline hydrochloride and is present at an amount of about 4% by weight of the composition.
21. The method of claim 19 , wherein the agent comprises at least one fatty alcohol, at least one fatty acid, and at least one wax.
22. The method of claim 19 , wherein the composition is a foam composition, and wherein the foam composition is produced upon addition of a liquefied or compressed gas propellant to the carrier.
23. The method of claim 19 , wherein the carrier comprises:
a) 45% to 55% by weight of a soybean oil;
b) 21.2% to 26% by weight of a coconut oil;
c) 4.5% to 5.5% by weight of a cyclomethicone;
d) 0.85% to 4.8% by weight of a light mineral oil;
e) 3.2% to 3.9% by weight of cetostearyl alcohol;
f) 2.7% to 3.3% by weight of stearic acid;
g) 2.3% to 2.8% by weight of myristyl alcohol;
h) 1.8% to 2.2% by weight of hydrogenated castor oil;
i) 1.8% to 2.2% by weight of beeswax;
j) 1.4% to 1.7% by weight of stearyl alcohol; and
k) 1% to 1.2% by weight of behenyl alcohol.