Oil and liquid silicone foamable carriers and formulations
View Patent ↗A waterless foamable pharmaceutical composition suitable for external administration is disclosed. The composition includes a foamable carrier least one liquefied or compressed gas propellant. The foamable carrier includes at least one liquid oil; at least one silicone and at least one least one stabilizing agent; wherein the stabilizing agent selected from the group consisting of about 0.01% to about 25% by weight of at least one surface-active agent alone or on combination with a foam adjuvant; and about 0% to about 5% by weight of at least one polymeric agent alone or on combination with a foam adjuvant; and mixtures thereof. Pharmaceutical compositions comprising active agents, methods for their preparation, propellants suitable for use with the carriers and uses thereof are further described.
1. An essentially waterless composition in a container, comprising a carrier and a liquefied or compressed gas propellant, wherein the carrier comprises:
a liquid oil;
about 0.5% to about 15% by weight of the carrier of a cyclic silicone;
at least one foam stabilizing agent comprising a co surfactant and/or a foam adjuvant or a surfactant comprising a fatty acid ester or a mixture of any two or more thereof; and
a minocycline or a doxycycline or both;
a solid wax or solid oil selected from a group consisting of a solid paraffin, a hydrogenated oil, a hydrogenated emollient, palmitic acid or mixtures of any two or more thereof;
wherein the ratio of the carrier to the propellant is 100:3 to 100:35;
wherein upon release of the composition from the container, a foam results that does not collapse immediately and is breakable on mechanical shear; and wherein the minocycline or the doxycycline is stable for at least 3 weeks at 25° C. in the essentially waterless composition.
2. The essentially waterless composition of claim 1 , wherein the liquid oil is about 60% to about 95% by weight of the carrier.
3. The essentially waterless composition of claim 1 , wherein the liquid oil is selected from the group consisting of a mineral oil, a MCT oil, a liquid paraffin, a vegetable oil, an essential oil, an organic oil, a lipid, or a mixture of two or more thereof.
4. The essentially waterless composition of claim 1 , wherein the stabilizing agent is about 0.01% to about 25% by weight of the carrier.
5. The essentially waterless composition of claim 1 , wherein the foam stabilizing agent comprises a monoglyceride, diglyceride, or triglyceride, or a mixture of any two or more thereof, wherein the side chain of the monoglyceride, diglyceride, or triglyceride is a saturated hydrocarbon.
6. The essentially waterless composition of claim 1 , wherein the co surfactant is selected from the group consisting of a sorbitan fatty acid ester, sorbitan monopalmitate, sorbitan monooleate, sorbitan monostearate, sorbitan monolaurate and a mixture of any two or more thereof.
7. The essentially waterless composition of claim 1 , wherein the composition further is essentially free of one or more of propylene glycol, glycerol, PEG 200, PEG 400, isostearic acid, polyoxyl 20 stearyl ether, polyoxyl 2 stearyl ether, methyl glycose sesquistearate, polysorbate 60, polysorbate 80 or sucrose distearate.
8. The essentially waterless composition of claim 1 , wherein the co-surfactant has an HLB of about 4 or less than about 4.
9. The essentially waterless composition of claim 1 , wherein the stabilizing agent comprises a glyceryl monostearate.
10. The essentially waterless composition of claim 1 , wherein the silicone is selected from the group consisting of a cyclomethicone, a cyclotetrasiloxane, a cyclopentasiloxane, a cyclohexasiloxane, and a mixture of any two or more thereof.
11. The essentially waterless composition of claim 1 , wherein the oil is a mixture of heavy mineral oil and light mineral oil having a weight ratio from about 1:5 to about 25:1.
12. The essentially waterless composition of claim 1 , further comprising an emollient selected from the group consisting of cocoglycerides, PPG 15 stearyl alcohol, octyldodecanol, isopropyl myristate, diisopropyl adipate, cetearyl octanoate isohexadecanol, diisopropyl adipate, and a mixture of any two or more thereof.
13. The essentially waterless composition of claim 1 , further comprising stearic acid, arachidic acid, behenic acid, or a mixture of any two or more thereof.
14. The essentially waterless composition of claim 1 , wherein the foam adjuvant comprises a fatty alcohol and a fatty acid.
15. The essentially waterless composition of claim 1 , wherein the foam stabilizing agent is the surfactant or co-surfactant in combination with a foam adjuvant selected from the group consisting of stearyl alcohol, cetyl alcohol, cetostearyl alcohol, myristyl alcohol, palmitoleyl alcohol, arachidyl alcohol, behenyl alcohol, and a mixture of any two or more thereof.
16. The essentially waterless composition of claim 1 , wherein the foam stabilizing agent is the surfactant in combination with the foam adjuvant, wherein the foam adjuvant comprises stearic acid.
17. The essentially waterless composition of claim 1 , wherein the weight ratio of foam stabilizing agent to silicone ranges from about 1:1 to about 1:4.
18. The essentially waterless composition of claim 2 , comprising by weight of the carrier: a) about 60-90% mineral oil; b) about 1-15% of a silicone, wherein the silicone is selected from the group consisting of a cyclomethicone, a cyclohexasiloxane, a cyclopentasiloxane, a cyclytetrasiloxane, and a mixture of any two or more thereof; c) about 1-8% glycerol monostearate; and d) about 1-8% of at least one of myristyl alcohol, stearyl alcohol, cetyl alcohol, cetostearyl alcohol, behenyl alcohol or cetostearyl alcohol.
19. An essentially waterless composition according to claim 1 , further comprising a further active agent in addition to a minocycline and or a doxycycline.
20. The essentially waterless composition according to claim 19 , wherein the further active agent is selected from the group consisting of active herbal extracts, acaricides, age spot removing agents, keratose removing agents, allergen, analgesics, local anesthetics, antiacne agents, antiallergic agents, antiaging agents, antibacterials, antibiotic agents, antiburn agents, anticancer agents, antidandruff agents, antidepressants, antidermatitis agents, antiedemics, antihistamines, antihelminths, antihyperkeratolyte agents, antiinflammatory agents, antiirritants, antilipemics, antimicrobials, antimycotics, antiproliferative agents, antioxidants, anti-wrinkle agents, antipruritics, antipsoriatic agents, antirosacea agents, antiseborrheic agents, antiseptic, antiswelling agents, antiviral agents, anti-yeast agents, astringents, topical cardiovascular agents, chemotherapeutic agents, corticosteroids, dicarboxylic acids, disinfectants, fungicides, hair growth regulators, hormones, hydroxy acids, immunosuppressants, immunoregulating agents, insecticides, insect repellents, keratolytic agents, lactams, metals, metal oxides, mitocides, neuropeptides, non-steroidal anti-inflammatory agents, oxidizing agents, pediculicides, photodynamic therapy agents, retinoids, scabicides, self tanning agents, skin whitening agents, vasoconstrictors, vasodilators, vitamin A, vitamin A derivatives, vitamin B, vitamin B derivatives, vitamin C, vitamin C derivatives, vitamin D, vitamin D derivatives, vitamin E, vitamin E derivatives, vitamin K, vitamin K derivatives wound healing agents, wart removers, and a mixture of any two or more thereof.
21. The essentially waterless composition according to claim 20 , wherein the additional active agent is selected from the group consisting of acyclovir, azaleic acid, clindamycin phosphate, pimicrolimus, diclofenac potassium, calcipotriol, calcitriol, vitamin A acetate, betamethasone 17-valerate, alpha tocopherol, imiquimod, ciclopiroxolamine, and a mixture of any two or more thereof.
22. The essentially waterless composition according to claim 1 , further comprising up to 5% or about 5% by weight of at least one polymeric agent.
23. The essentially waterless composition according to claim 1 , wherein the resultant foam displays all of the following characteristics: a) does not collapse immediately upon release; b) is breakable on mechanical shear; c) has a viscosity below about 13,000 cps; d) has an average bubble size below 200 microns; e) has a hardness between about 5 to about 35; f) has a collapse time in excess of about 180 seconds; and g) has a density below about 0.2 g/ml.
24. A method for treating or ameliorating a disorder comprising administering to a target site a pharmaceutically effective amount of the essentially waterless composition according to claim 1 , wherein the target site is selected from the group consisting of the skin, a body cavity, a mucosal surface, the nose, the mouth, the eye, the ear canal, the vagina, and the rectum, wherein the disorder is selected from a group consisting of acne, rosacea and impetigo.
25. A method according to claim 24 , wherein the essentially waterless composition comprises at least one additional active agent selected from a group consisting of active herbal extracts, analgesics, local anesthetics, antiacne agents, antiallergic agents, antibacterials, antibiotic agents, antiburn agents, antidermatitis agents, antihistamines, antiinflammatory agents, antiirritants, antimicrobials, antipruritics, antiseborrheic agents, antiseptic, antiswelling agents, antiviral agents, anti-yeast agents, corticosteroids, dicarboxylic acids, disinfectants, fungicides, hormones, metals, metal oxides, non-steroidal anti-inflammatory agents, retinoids, vitamin B, vitamin B derivatives, vitamin C, vitamin C derivatives, vitamin D, vitamin D derivatives, vitamin E, vitamin E derivatives, wound healing agents, acyclovir, azaleic acid, clindamycin phosphate, pimicrolimus, diclofenac potassium, calcipotriol, calcitriol, betamethasone 17-valerate, alpha tocopherol, ciclopiroxolamine, and a mixture of any two or more thereof and a mixture of any two or more thereof.
26. An essentially waterless composition in a container, comprising a carrier, wherein the carrier comprises:
a liquid oil;
about 0.5% to about 15% by weight of the carrier of a cyclic silicone;
at least one foam stabilizing agent comprising a co surfactant and/or a foam adjuvant or a surfactant comprising a fatty acid ester or a mixture of any two or more thereof and a minocycline or a doxycycline or both;
a solid wax or solid oil selected from a group consisting of a solid paraffin, a hydrogenated oil, a hydrogenated emollient, palmitic acid or mixtures of any two or more thereof;
wherein the liquid oil is about 60% to about 95% by weight of the carrier;
wherein the foam stabilizing agent is selected from the group consisting of about 0.1% to about 25% by weight of at least one surface-active agent alone or in combination with a foam adjuvant;
and wherein the minocycline or the doxycycline is stable for at least 3 weeks at 25° C. in the essentially waterless composition.
27. A method according to claim 24 , wherein the essentially waterless composition comprises at least one additional active agent useful for treating acne, rosacea, or impetigo.