Oil-based foamable carriers and formulations
View Patent ↗A waterless foamable carrier and pharmaceutical composition which is suitable for external and internal administration is disclosed. The composition is single phase and includes at least one liquid oil; and a glyceride. Pharmaceutical compositions comprising active agents, methods for their preparation, propellants suitable for use with the carriers and uses thereof are further described.
1. A foamable pharmaceutical composition, comprising a foamable carrier and a propellant in a container, wherein the foamable carrier comprises:
a. about 60% to about 98% by weight of the foamable carrier of a liquid oil comprising a mixture of a mineral oil and one or more liquid oils selected from the group consisting of a medium chain triglyceride oil, a vegetable oil, an essential oil and a silicone oil;
b. about 2% to about 40% by weight of the foamable carrier of a surfactant, wherein the surfactant comprises at least one glyceride; and
c. a wax selected from the group consisting of beeswax, hydrogenated castor oil, candelilla wax, and a mixture of any two or more thereof;
wherein the composition comprises less than 1.5% water,
wherein the foamable carrier is capable of producing a foam having a specific gravity in the range of 0.05 to 0.20,
wherein the foamable carrier is selected to produce a foam having a collapse time in excess of about 180 seconds, and wherein the composition does not include a polymer stabilizer.
2. The foamable composition of claim 1 , wherein the carrier further comprises an additive selected from the group consisting of a foam adjuvant, a thickener, a phospholipid, and a mixture of any two or more thereof.
3. The foamable composition of claim 1 , wherein the average bubble size of the foam is less than about 200 microns.
4. The foamable composition of claim 1 , wherein the composition further comprises a surfactant selected from the group consisting of a a polysorbate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan monooleate, a polyoxyethylene fatty acid ester, polyoxyethylene (8) stearate, polyoxyethylene (20) stearate, polyoxyethylene (40) stearate, polyoxyethylene (100) stearate, a polyoxyethylene alkyl ether, polyoxyethylene cetyl ether, a steareth, steareth 2, steareth 21, polyoxyethylene (23) cetyl ether, polyoxyethylene (2) cetyl ether, polyoxyethylene (10) cetyl ether, a sucrose ester, a partial ester of sorbitol and its anhydrides, sorbitan monolaurate, isoceteth-20 and mono-, and di- and triesters of sucrose with fatty acids, and a mixture of any two or more thereof.
5. The foamable composition of claim 1 , wherein the weight ratio of the light mineral oil to the heavy mineral oil ranges from about 1:1 to about 1:2.
6. The foamable composition of claim 1 , wherein the liquid oil is a mixture of a vegetable oil, a mineral oil, and a silicone oil.
7. The foamable composition of claim 2 , wherein the additive is a foam adjuvant, which is selected from the group consisting of a fatty alcohol, a fatty acid a hydroxyl fatty acid and a mixture thereof.
8. The foamable composition of claim 1 , further comprising an active agent.
9. The foamable composition according to claim 8 , wherein the foamable carrier including the active agent is a homogenous suspension.
10. The foamable composition according to claim 8 , wherein the active agent is soluble in the liquid oil or the carrier.
11. The foamable composition of claim 8 , wherein the active agent is selected from the group consisting of a tetracycline antibiotic agent, an acaricide, an active herbal extract, 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 anent, 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 anti-yeast agent, an astringent, a beta-hydroxy acid, benzoyl peroxide, a 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 progesterone, a protein, a photodynamic therapy agent, a radical scavenger, a refatting agent, a retinoid, a sedative agent, a scabicide, 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 B, a vitamin C, a vitamin D, a vitamin D analog, a vitamin F, a vitamin K,-acyclovir, azelaic acid, clindamycin phosphate, pimecrolimus, diclofenac potassium, calcipotriol, calcitriol, vitamin A acetate, betamethasone 17-valerate, alpha tocopherol, imiquimod, ciclopiroxolamine, a wound healing agent, a wart remover, and a mixture of any two or more thereof.
12. The foamable composition of claim 11 , wherein the tetracycline antibiotic agent is selected from the group consisting of a minocycline, a doxycycline and a mixture of any two or more thereof.
13. The foamable composition of claim 8 , wherein the active agent is selected from the group consisting of acyclovir, azelaic acid, clindamycin phosphate, pimecrolimus, diclofenac potassium, calcipotriol, calcitriol, vitamin A acetate, betamethasone 17-valerate, alpha tocopherol, imiquimod, ciclopiroxolamine, and a mixture of any two or more thereof.
14. The foamable composition of claim 1 , wherein the composition further comprises one or more additional components selected from the group consisting of an anti-perspirant, an anti-static agent, a buffering agent, an anti-oxidant, a free radical scavenger, a bulking agent, a chelating agent, a cleanser, a colorant, a conditioner, a deodorant, a diluent, a dye, a fragrance, a hair conditioner, a humectant, a modulating agent, a pearlescent aid, a perfuming agent, a permeation enhancer, a pH-adjusting agent, an occlusive agent, a preservative, a protectant, a skin penetration enhancer, a softener, a solubilizer, a sunscreen, a sun blocking agent, a sunless tanning agent, a viscosity modifier, and a vitamin.
15. The foamable composition of claim 1 , wherein the carrier does not include a foam adjuvant.
16. The foamable composition of claim 1 , wherein the ratio of the foamable carrier to the propellant is from about 100:3 by weight to about 100:35 by weight.
17. The foamable composition of claim 16 wherein the propellant is selected from the group consisting of a liquefied propellant, a compressed gas propellant, a hydrocarbon propellant, a hydrofluorocarbon propellant, and a mixture of any two or more propellants.
18. A foamable pharmaceutical composition, comprising a foamable carrier and a propellant in a container, wherein the foamable carrier comprises:
a. about 60% to about 98% by weight of the foamable carrier of a liquid oil comprising a mixture of a mineral oil and one or more liquid oils selected from the group consisting of a medium chain triglyceride oil, a vegetable oil, an essential oil and a silicone oil;
b. about 0.2% to about 8% by weight of the foamable carrier of a surfactant wherein the surfactant comprises at least one glyceride; and
c. a wax selected from the group consisting of beeswax, hydrogenated castor oil, candelilla wax, and a mixture of any two or more thereof; and
wherein the composition comprises less than 1.5% water,
wherein the foamable carrier is capable of producing a foam having a specific gravity in the range from 0.05 to 0.20,
wherein the foamable carrier is selected to produce a foam having a collapse time in excess of about 180 seconds, and
wherein the composition does not include a polymer stabilizer.
19. A method for skin, mucosal surface or body cavity treatment, comprising releasing the foamable composition of claim 8 to form a breakable foam and administering the foam to skin, a mucosal surface or a body cavity having a disorder needing treatment.
20. The method of claim 19 , wherein the active agent is present in a therapeutically effective amount to treat the disorder, and wherein the disorder is selected from the group consisting of a skin, body cavity, mucosal membrane, ear channel, eye, nasal, oral, respiratory, vaginal, rectal, or urethra disorder, dermatological pain, dermatological inflammation, acne, acne vulgaris, inflammatory acne, non-inflammatory acne, acne fulminans, nodular papulopustular acne, acne conglobata, dermatitis, bacterial skin infection, fungal skin infection, viral skin infection, parasitic skin infection, skin neoplasia, skin neoplasms, pruritis, cellulitis, acute lymphangitis, lymphadenitis, erysipelas, cutaneous abscess, necrotizing subcutaneous infection, scalded skin syndrome, folliculitis, furuncles, hidradenitis suppurativa, carbuncle, paronychial infections, rash, erythrasma, impetigo, ecthyma, yeast skin infection, a wart, molluscum contagiosum, trauma or injury to the skin, post-operative or post-surgical skin condition, scabies, pediculosis, creeping eruption, eczemas, psoriasis, pityriasis rosea, lichen planus, pityriasis rubra pilaris, edematous, erythema multiforme, erythema nodosum, grannuloma annulare, epidermal necrolysis, sunburn, photosensitivity, pemphigus, bullous pemphigoid, dermatitis herpetiformis, keratosis pilaris, callouses, corns, ichthyosis, a skin ulcer, ischemic necrosis, miliaria, hyperhidrosis, a mole, Kaposi's sarcoma, melanoma, malignant melanoma, basal cell carcinoma, squamous cell carcinoma, poison ivy, poison oak, contact dermatitis, atopic dermatitis, rosacea, purpura, moniliasis, candidiasis, baldness, alopecia, Behcet's syndrome, cholesteatoma, Dercum disease, ectodermal dysplasia, gustatory sweating, nail patella syndrome, lupus, hives, hair loss, Hailey-Hailey disease, a chemical or thermal skin burn, scleroderma, aging skin, a wrinkle, a sun spot, necrotizing fasciitis, necrotizing myositis, gangrene, scarring, and vitiligo, chlamydia infection, gonorrhea infection, hepatitis B, herpes, HIV/AIDS, human papillomavirus (HPV), a genital wart, bacterial vaginosis, candidiasis, chancroid, granuloma Inguinale, lymphogranloma venereum, mucopurulent cervicitis (MPC), molluscum contagiosum, nongonococcal urethritis (NGU), trichomoniasis, vulvar disorders, vulvodynia, vulvar pain, yeast infection, vulvar dystrophy, vulvar intraepithelial neoplasia (VIN), contact dermatitis, pelvic inflammation, endometritis, salpingitis, oophoritis, a genital cancer, a cancer of the cervix, a cancer of the vulva, a cancer of the vagina, vaginal dryness, dyspareunia, an anal and rectal disease, anal abscess/fistula, an anal cancer, an anal fissure, an anal wart, Crohn's disease, hemorrhoids, anal itch, pruritus ani, fecal incontinence, constipation, a polyp of the colon and rectum, bacterial infection, a fungal infection, a yeast infection, a viral infection and a parasitic infection, wound, ulcer and burn, any disorder that responds to treatment with a hormone, a post-surgical adhesion, acne, and rosacea.
21. The foamable composition of claim 7 , wherein:
the vegetable oil comprises a coconut oil, a soybean oil, or a mixture thereof;
the silicone oil comprises a cyclomethicone;
the surfactant comprises glyceryl monostearate;
the foam adjuvant comprises stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, myristyl alcohol, or a mixture of any two or more thereof; and
the wax comprises beeswax, hydrogenated castor oil or a mixture thereof.
22. The foamable composition of claim 1 , wherein the mineral oil comprises a liquid paraffin.
23. A foamable pharmaceutical composition, comprising a foamable carrier and a propellant in a container, the foamable carrier comprising:
a. about 60% to about 98% by weight of the foamable carrier of a liquid oil comprising a mixture of a mineral oil and one or more liquid oils selected from the group consisting of a medium chain triglyceride oil, a vegetable oil, an essential oil and a silicone oil;
b. about 2% to about 40% by weight of the foamable carrier of a surfactant wherein the surfactant comprises at least one glyceride;
c. a wax selected from the group consisting of beeswax, hydrogenated castor oil, candelilla wax, and a mixture of any two or more thereof;
d. a foam adjuvant selected from the group consisting of a fatty alcohol, a fatty acid a hydroxyl fatty acid and a mixture thereof; and
e. an active agent comprising a tetracycline antibiotic selected from the group consisting of a minocycline, a doxycycline and a mixture of any two or more thereof; and
wherein the composition comprises less than 1.5% water,
wherein the foamable carrier is capable of producing a foam having a specific gravity in the range from 0.05 to 0.20,
wherein the foamable carrier is selected to produce a foam having a collapse time in excess of about 180 seconds, and
wherein the composition does not include a polymer stabilizer.
24. The foamable composition of claim 18 , wherein the carrier further comprises an additive selected from the group consisting of a foam adjuvant, a thickener, a phospholipid, and a mixture of any two or more thereof.
25. The foamable composition of claim 24 , wherein the additive is a foam adjuvant, which is selected from the group consisting of a fatty alcohol, a fatty acid a hydroxyl fatty acid and a mixture thereof.
26. The foamable composition of claim 25 , wherein:
the vegetable oil comprises a coconut oil, a soybean oil, or a mixture thereof;
the silicone oil comprises a cyclomethicone;
the surfactant comprises glyceryl monostearate;
the foam adjuvant comprises stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, myristyl alcohol, or a mixture of any two or more thereof; and
the wax comprises beeswax, hydrogenated castor oil or a mixture thereof.
27. The foamable composition of claim 1 , wherein the one or more liquid oils is selected from the group consisting of a medium chain triglyceride oil, a vegetable oil, an essential oil, and a mixture of any two thereof.
28. The foamable composition of claim 18 , wherein the one or more liquid oils is selected from the group consisting of a medium chain triglyceride oil, a vegetable oil, an essential oil, and a mixture of any two thereof.
29. The foamable pharmaceutical composition of claim 23 , wherein the one or more liquid oils is selected from the group consisting of a medium chain triglyceride oil, a vegetable oil, an essential oil and a mixture of any two thereof.
30. The foamable pharmaceutical composition of claim 1 , further comprising a solid or semi solid oil.
31. The foamable pharmaceutical composition of claim 18 , further comprising a solid or semi solid oil.
32. The foamable pharmaceutical composition of claim 23 , further comprising a solid or semi solid oil.
33. The foamable pharmaceutical composition of claim 1 , wherein the at least one glyceride is a monoglyceride, a diglyceride, or a triglyceride.
34. The foamable pharmaceutical composition of claim 1 , wherein the at least one glyceride comprises a sidechain that is a hydrocarbon having from 8 to 24 carbon atoms.
35. The foamable pharmaceutical composition of claim 1 , further comprising a surfactant selected from the group consisting of a peg 40 stearate, a polysorbate 80, a sorbitan stearate, a sorbitan monooleate, a ceteareth 20, a steareth 20, a ceteth 20, a ceteth 2, a PEG-30 dipolyhydroxystearate, a sucrose distearate, a polyoxyethylene (100) stearate, a PEG-30 stearate, a PEG-40 laurate, a PEG-40 oleate, a PEG-45 stearate, a PEG-50 stearate, a PEG-100 stearate, a PEG-4 dilaurate, a PEG-4, a PEG-32 dioleate, a PEG-400 dioleate, a PEG-400 distearate, a PEG-20 glyceryl monooleate, a PEG-30 castor oil, a PEG-40 hydrogenated castor oil, a polyglyceryl-6-dioleate, a PEG-20 sorbitan monolaurate, a PEG-20 sorbitan monopalmitate, a PEG-20 sorbitan monostearate, a PEG-20 sorbitan monooleate, a sucrose distearate, a cetearyl alcohol, a cetearyl glucoside, a C14-C22 alkyl alcohol, a C12-C20 alkyl glucoside, a glyceryl distearate, a glyceryl monooleate, and a lecithin.
36. The foamable pharmaceutical composition of claim 1 , wherein the surfactant comprises glyceryl monostearate.
37. The foamable pharmaceutical composition of claim 1 , wherein the glyceride is saturated.