Topical tetracycline compositions
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. 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. The composition is packaged as a breakable foam that breaks easily upon application of shear force.
1. A foamable, waterless, surfactant-free composition comprising a carrier and a liquefied or compressed gas propellant, the carrier comprising:
a) a tetracycline antibiotic;
b) a combination of two or more hydrophobic oils, wherein at least one of the hydrophobic oils is a light mineral oil and the other hydrophobic oil comprises a heavy mineral oil, soybean oil, and/or coconut oil;
c) a combination of two or more fatty alcohols, wherein at least one of the fatty alcohols is stearyl alcohol;
d) optionally stearic acid; and
e) wherein the carrier comprises at least one wax;
wherein the hydrophobic oils are present at between about 70% and 95% by weight of the carrier;
wherein ratio of the fatty alcohols to stearic acid, if present, is between about 4:1 and 1:4;
wherein the fatty alcohols and the wax are present at a ratio between about 4:1 and 3:2;
wherein the ratio of the carrier to the propellant is between about 100:1 and about 100:25; and wherein upon release from an aerosol container, the composition forms a foam.
2. The foamable composition of claim 1 , wherein the wax is selected from the group consisting of a beeswax, a hydrogenated castor oil, a paraffin 58-62° C. wax, paraffin 51-53° C. wax, a paraffin 42-44° C. wax, and a mixture of two or more thereof.
3. The foamable composition of claim 1 , wherein the combination of the hydrophobic oils comprises (1) a light mineral oil and (2) one or more hydrophobic oils selected from the group consisting of a heavy mineral oil, a hydrocarbon oil, an ester oil, an ester of a dicarboxylic acid, a triglyceride oil, an oil of plant origin, an oil from animal origin, an unsaturated or polyunsaturated oil, a diglyceride, a PPG alkyl ether, an essential oil, a silicone oil, liquid paraffin, an isoparaffin, a polyalphaolefin, a polyolefin, polyisobutylene, a synthetic isoalkane, isohexadecane, isododecane, alkyl benzoate, alkyl octanoate, C12-C15 alkyl benzoate, C12-C15 alkyl octanoate, arachidyl behenate, arachidyl propionate, benzyl laurate, benzyl myristate, benzyl palm itate, bis (octyldodecyl stearoyl) dimer dilinoleate, butyl myristate, butyl stearate, cetearyl ethyl hexanoate, cetearyl isononanoate, cetyl acetate, cetyl ethylhexanoate, cetyl lactate, cetyl myristate, cetyl octanoate, cetyl palm itate, cetyl ricinoleate, decyl oleate, diethyleneglycol diethylhexanoate, diethyleneglycol dioctanoate, diethyleneglycol diisononanoate, diethyleneglycol diisononanoate, diethylhexanoate, diethylhexyl adipate, diethylhexyl malate, diethylhexyl succinate, diisopropyl adipate, diisopropyl dimerate, diisopropyl sebacate, diisosteary dimer dilinoleate, diisostearyl fumerate, dioctyl malate, dioctyl sebacate, dodecyl oleate, ethylhexyl palm itate, ester derivatives of lanolic acid, ethylhexyl cocoate, ethylhexyl ethylhexanoate, ethylhexyl hydroxystarate, ethylhexyl isononanoate, ethylhexyl palmytate, ethylhexyl pelargonate, ethylhexyl stearate, hexadecyl stearate, hexyl laurate, isoamyl laurate, isocetyl isocetyl behenate, isocetyl lanolate, isocetyl palm itate, isocetyl stearate, isocetyl salicylate, isocetyl stearate, isocetyl stearoyl stearate, isocetearyl octanoate, isodecyl ethylhexanoate, isodecyl isononanoate, isodecyl oleate, isononyl isononanoate, isodecyl oleate, isohexyl decanoate, isononyl octanoate, isopropyl isostearate, isopropyl lanolate, isopropyl laurate, isopropyl myristate, isopropyl palm itate, isopropyl stearate, isostearyl behenate, isosteary citrate, isostearyl erucate, isostearyl glycolate, isostearyl isononanoate, isostearyl isostearate, isostearyl lactate, isostearyl linoleate, isostearyl linolenate, isostearyl malate, isostearyl neopentanoate, isostearyl palm itate, isosteary salicylate, isosteary tartarate, isotridecyl isononanoate, isotridecyl isononanoate, lauryl lactate, myristyl lactate, myristyl myristate, myristyl neopentanoate, myristyl propionate, octyldodecyl myristate, neopentylglycol dicaprate, octyl dodecanol, octyl stearate, octyl palmitate, octyldodecyl behenate, octyldodecyl hydroxystearate, octyldodecyl myristate, octyldodecyl stearoyl stearate, oleyl erucate, oleyl lactate, oleyl oleate, propyl myristate, propylene glycol myristyl ether acetate, propylene glycol dicaprate, propylene glycol dicaprylate, maleated soybean oil, stearyl caprate, stearyl heptanoate, stearyl propionate, tocopheryl acetate, tocopheryl linoleate, glyceryl oleate, tridecyl ethylhexanoate, tridecyl isononanoate, triisocetyl citrate, an alexandria laurel tree oil, an avocado oil, an apricot stone oil, a barley oil, a borage seed oil, a calendula oil, a canelle nut tree oil, a canola oil, caprylic/capric triglycerides, a castor oil, a coconut oil, a corn oil, a cotton oil, a cottonseed oil, an evening primrose oil, a flaxseed oil, a groundnut oil, a hazelnut oil, glycereth triacetate, glycerol triheptanoate, glyceryl trioctanoate, glyceryl triundecanoate, a hempseed oil, a jojoba oil, a lucerne oil, a maize germ oil, a marrow oil, a millet oil, a neopentylglycol dicaprylate/dicaprate, an olive oil, a palm oil, a passionflower oil, pentaerythrityl tetrastearate, a poppy oil, propylene glycol ricinoleate, a rapeseed oil, a rye oil, a safflower oil, a sesame oil, a shea butter, a soya oil, a soybean oil, a sweet almond oil, a sunflower oil, a sysymbrium oil, a syzigium aromaticum oil, a tea tree oil, a walnut oil, wheat germ glycerides, a wheat germ oil, a PPG-2 butyl ether, a PPG-4 butyl ether, a PPG-5 butyl ether, a PPG-9 butyl ether, a PPG-12 butyl ether, a PPG-14 butyl ether, a PPG-15 butyl ether, a PPG-15 stearyl ether, a PPG-16 butyl ether, a PPG-17 butyl ether, a PPG-18 butyl ether, a PPG-20 butyl ether, a PPG-22 butyl ether, a PPG-24 butyl ether, a PPG-26 butyl ether, a PPG-30 butyl ether, a PPG-33 butyl ether, a PPG-40 butyl ether, a PPG-52 butyl ether, a PPG-53 butyl ether, a PPG-10 cetyl ether, a PPG-28 cetyl ether, a PPG-30 cetyl ether, a PPG-50 cetyl ether, a PPG-30 isocetyl ether, a PPG-4 lauryl ether, a PPG-7 lauryl ether, a PPG-2 methyl ether, a PPG-3 methyl ether, a PPG-3 myristyl ether, a PPG-4 myristyl ether, a PPG-10 oleyl ether, a PPG-20 oleyl ether, a PPG-23 oleyl ether, a PPG-30 oleyl ether, a PPG-37 oleyl ether, a PPG-40 butyl ether, a PPG-50 oleyl ether, a PPG-11 stearyl ether, a herring oil, a cod-liver oil, a salmon oil, a cyclomethicone, a dimethyl polysiloxane, a dimethicone, an epoxy-modified silicone oil, a fatty acid-modified silicone oil, a fluoro group-modified silicone oil, a methylphenylpolysiloxane, phenyl trimethicone, and a polyether group-modified silicone oil.
4. The foamable composition of claim 1 , wherein the combination of the hydrophobic oils comprises a light mineral oil and a heavy mineral oil.
5. The foamable composition of claim 4 , wherein the ratio between the heavy mineral oil and the light mineral oil is equal to or less than about 2.4:1.
6. The foamable composition of claim 1 , wherein the hydrophobic oils comprise a light mineral oil, a soybean oil, a coconut oil, and cyclomethicone.
7. The foamable composition of claim 6 , wherein cyclomethicone is present at about 5% by weight of the carrier or less.
8. The foamable composition of claim 1 , wherein the combination of fatty alcohols comprises (1) stearyl alcohol and (2) one or more fatty alcohols selected from the group consisting of cetyl alcohol, cetostearyl alcohol, behenyl alcohol, and myristyl alcohol.
9. The foamable composition of claim 1 , wherein the combination of fatty alcohols comprises stearyl alcohol and cetostearyl alcohol.
10. The foamable composition of claim 1 , wherein the combination of fatty alcohols comprises stearyl alcohol and behenyl alcohol.
11. The foamable composition of claim 10 , wherein behenyl alcohol is present at about 5% by weight of the carrier or less.
12. The foamable composition of claim 1 , wherein the combination of fatty alcohols comprises stearyl alcohol, cetostearyl alcohol, behenyl alcohol, and myristyl alcohol.
13. The foamable composition of claim 12 , wherein behenyl alcohol is present at about 5% by weight of the carrier or less.
14. The foamable composition of claim 1 , wherein the fatty alcohols and stearic acid are present at about 1% to about 12% by weight of the carrier.
15. The foamable composition of claim 1 , wherein the tetracycline antibiotic is selected from the group consisting of an oxytetracycline, a demeclocycline, a doxycycline, a lymecycline, a meclocycline, a methacycline, a minocycline, a rolitetracycline, a chlorotetracycline, a tigecycline, and a mixture of two or more thereof.
16. The foamable composition of claim 1 , wherein the tetracycline antibiotic comprises minocycline.
17. The foamable composition of claim 16 , wherein the minocycline is present as a free base, a hydrate, a salt, or a complex.
18. The foamable composition of claim 1 , wherein the tetracycline antibiotic is micronized.
19. The foamable composition of claim 1 , wherein the tetracycline antibiotic is present at about 0.025% to about 6% by weight of the carrier.
20. The foamable composition of claim 1 , further comprising an additional active agent.
21. The foamable composition of claim 20 , wherein the additional active agent is selected form the group consisting of an active herbal extract, an acaricide, an age spot and keratose removing agent, an allergen, an alpha hydroxyl acid, an analgesic agent, an androgen, an antiacne agent, an antiallergic agent, an antiaging agent, an antibacterial agent, an antibiotic, an antiburn agent, an anticancer agent, an antidandruff agent, an antidepressant, an antidermatitis agent, an antiedemic agent, an antifungal agent, an antihistamine, an antihelminth agent, an anti-hyperkeratosis agent, an anti-infective agent, an antiinflammatory agent, an antiirritant, an antilipemic agent, an antimicrobial agent, an antimycotic agent, an antioxidant, an antiparasitic agent, an antiproliferative agent, an antipruritic agent, an antipsoriatic agent, an antirosacea agent, an antiseborrheic agent, an antiseptic agent, an antiswelling agent, an antiviral agent, an anti-wart agent, an anti-wrinkle agent, an antiyeast agent, an astringent, a beta-hydroxy acid, benzoyl peroxide, a topical cardiovascular agent, a chemotherapeutic agent, a corticosteroid, an immunogenic substance, a dicarboxylic acid, a disinfectant, an estrogen, a fungicide, a hair growth regulator, a haptene, a hormone, a hydroxy acid, an immunosuppressant, an immunoregulating agent, an immunomodulator, an immunostimulant, an insecticide, an insect repellent, a keratolytic agent, a lactam, a local anesthetic agent, a lubricating agent, a masking agent, a metal, a metal oxide, a mitocide, a neuropeptide, a non-steroidal anti-inflammatory agent, an oxidizing agent, a pediculicide, a peptide, a pesticide, a protein, a photodynamic therapy agent, a progesterone, a radical scavenger, a refatting agent, a retinoid, a sanative, a scabicide, a sedative, a self tanning agent, a skin protective agent, a skin whitening agent, a steroid, a steroid hormone, a vasoactive agent, a vasoconstrictor, a vasodilator, a vitamin, a vitamin A, a vitamin A derivative, a vitamin B, a vitamin B derivative, a vitamin C, a vitamin C derivative, a vitamin D, a vitamin D derivative, a vitamin D analog, a vitamin F, a vitamin F derivative, a vitamin K, a vitamin K derivative, a wound healing agent, and a wart remover and a mixture of two or more thereof.
22. The foamable composition of claim 20 , wherein the additional active agent is a retinoid.
23. The foamable composition of claim 20 , wherein the additional active agent is benzoyl peroxide.
24. The foamable composition of claim 20 , wherein the additional active agent is selected from the group consisting of an antiparasitic agent, a steroid, an antihistamine, a vasoconstrictor, and a mixture of two or more thereof.
25. The foamable composition of claim 1 , wherein the carrier further comprises silicon dioxide.
26. The foamable composition of claim 25 , wherein silicone dioxide is present at about 0.25% by weight of the carrier or less.
27. The foamable composition of claim 1 , wherein the composition retains at least about 90% of the tetracycline antibiotic initially present in the composition after storage at 25° C. for at least six months.
28. The foamable composition of claim 1 , wherein the foam does not collapse for at least about 180 seconds upon incubation at 36° C.
29. The foamable composition of claim 1 , wherein the foam comprises bubbles having an average diameter of less than about 150 micrometers.
30. The foamable composition of claim 1 , wherein the composition comprises less than 5% by weight of a silicone elastomer.
31. The foamable composition of claim 1 , wherein the ratio of the fatty alcohols to stearic acid, if present, is between about 4:1 and about 1:1.
32. A method of treating or alleviating the symptoms of a dermatological, ophthalmological, gynecological, or mucosal disorder, comprising applying to a patient in need thereof the foam of claim 1 .