Oil foamable carriers and formulations

Abstract

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 . (canceled) 
     
     
         2 . A foamable pharmaceutical composition, comprising a carrier and at least one liquefied or compressed gas propellant, wherein the carrier comprises:
 a) a solid wax or a solid oil;   b) at least one liquid oil;   c) at least one foam stabilizing agent; and   d) a minocycline or a doxycycline or both;   wherein the composition is substantially water-free;   wherein the ratio of the carrier to the propellant is 100:3 to 100:35;   wherein the resultant foam does not collapse immediately upon release 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 foamable pharmaceutical composition.   
     
     
         3 . The foamable pharmaceutical composition according to  claim 2 , wherein the liquid oil is present in an amount ranging from about 60% to about 95% by weight of the carrier. 
     
     
         4 . The foamable pharmaceutical composition according to  claim 2 , wherein the at least one liquid oil is selected from a mineral oil, a MCT oil, a liquid paraffin, a vegetable oil, an essential oil, an organic oil, a lipid, and a mixture thereof. 
     
     
         5 . The foamable pharmaceutical composition according to  claim 2 , wherein the carrier further comprises a silicone in an amount of about 0.5% to about 15% by weight. 
     
     
         6 . The foamable pharmaceutical composition according to  claim 5 , wherein the silicone is selected from a cyclic silicone, a branched silicone, a polar silicone and a mixture thereof. 
     
     
         7 . The foamable pharmaceutical composition according to  claim 6 , wherein the silicone is selected from a siloxane compound having 4-6 Si—O groups in its backbone, a cyclomethicone, a cyclotetrasiloxane, a cyclopentasiloxane, a cyclohexasiloxane, a phenyl trimethicone, a stearyl dimethicone, a cetyl dimethicone, a caprylyl methicone, a PEG/PPG 18/18 dimethicone, a dimethiconol, and a mixture thereof. 
     
     
         8 . The foamable pharmaceutical composition according to  claim 5 , wherein the silicone is a volatile silicon selected from a volatile short chain linear silicone fluid having in its molecule only methyl groups, a volatile cyclic silicone fluid having in its molecule only methyl groups, a volatile short chain linear silicone fluid having in its molecule both methyl groups and phenyl groups, and a volatile short chain linear silicone fluid having in its molecule both methyl groups and alkyl groups containing up to twelve carbon atoms. 
     
     
         9 . The foamable pharmaceutical composition of  claim 5 , wherein the weight ratio of foam stabilizing agent to silicone ranges from about 1:1 to about 1:4. 
     
     
         10 . The foamable pharmaceutical composition according to  claim 2 , wherein the foam stabilizing agent is about 0.01% to about 25% by weight of the carrier and is selected from a co surfactant, a surface-active agent, a foam adjuvant, and a mixture thereof. 
     
     
         11 . The foamable pharmaceutical composition according to  claim 10 , wherein the surface active agent is selected from a stearic acid derived ester, a monoglyceride, a diglyceride, a triglyceride, a glycerol monostearate, a glycerol palmitostearate, PEG 100 stearate, Montanov L, Montano 68, PPG 15 stearyl ether, and a mixture thereof. 
     
     
         12 . The foamable pharmaceutical composition according to  claim 10 , wherein the foam adjuvant is selected from stearyl alcohol, cetyl alcohol, cetostearyl alcohol, myristyl alcohol, palmitoleyl alcohol, arachidyl alcohol, benzyl alcohol, behenyl alcohol, oleyl alcohol, and a mixture thereof. 
     
     
         13 . The foamable pharmaceutical composition according to  claim 10 , wherein the foam stabilizing agent is a surfactant in combination with a foam adjuvant. 
     
     
         14 . The foamable pharmaceutical composition according to  claim 2 , further comprising an emollient selected from cocoglycerides, PPG 15 stearyl alcohol, octyldodecanol, isopropyl myristate, diisopropyl adipate, cetearyl octanoate isohexadecanol, diisopropyl adipate, and a mixture thereof. 
     
     
         15 . The foamable pharmaceutical composition according to  claim 2 , further comprising an active agent selected from 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 thereof. 
     
     
         16 . The foamable pharmaceutical composition according to  claim 2 , further comprising at least one polymeric agent in an amount of up to about 5% by weight. 
     
     
         17 . The foamable pharmaceutical composition according to  claim 2 , wherein the oil is a mixture of heavy mineral oil and light mineral oil having a weight ratio of the heavy mineral oil to the light mineral oil ranging from about 1:5 to about 25:1. 
     
     
         18 . The foamable pharmaceutical composition according to  claim 2 , wherein the solid wax or oil is selected from a solid paraffin, a hydrogenated oil, a hydrogenated emollient, palmitic acid, stearic acid, arachidic acid, behenic acid, hydrogenated castor oil, beeswax, and a mixture thereof. 
     
     
         19 . The foamable pharmaceutical composition according to  claim 2 , wherein the foam stabilizing agent comprises glycerol monostearate. 
     
     
         20 . The foamable pharmaceutical composition according to  claim 2 , wherein the carrier is substantially a single phase. 
     
     
         21 . The foamable pharmaceutical composition according to  claim 2 , wherein the solid wax or solid oil is present in an amount ranging from about 1.5% to about 5.75% by weight of the carrier. 
     
     
         22 . The foamable pharmaceutical composition according to  claim 2 , wherein the foam is spreadable and/or collapsible on a skin surface or a mucosal surface. 
     
     
         23 . The foamable pharmaceutical composition according to  claim 4 , wherein the at least one liquid oil is selected from an olive oil, a corn oil, a soybean oil, a canola oil, a cottonseed oil, a coconut oil, a sesame oil, a sunflower oil, a borage seed oil, a syzigium  aromaticum  oil, a hempseed oil, a flaxseed oil, a wheat germ oil, an evening primrose oil, an essential oil, and a mixture thereof. 
     
     
         24 . A method of treating or ameliorating a disorder, comprising administering to a target site a foam produced from the foamable composition according to  claim 2 , wherein the target site is a skin surface, a body cavity, or a mucosal surface, of a subject having said disorder. 
     
     
         25 . The method according to  claim 24 , wherein the disorder is selected from dermatological pain, dermatological inflammation, acne, acne vulgaris, inflammatory acne, non-inflammatory acne, acne fulminans, nodular papulopustular acne, acne conglobata, dermatitis, bacterial skin infections, fungal skin infections, viral skin infections, parasitic skin infections, skin neoplasia, skin neoplasms, pruritis, cellulitis, acute lymphangitis, lymphadenitis, erysipelas, cutaneous abscesses, necrotizing subcutaneous infections, scalded skin syndrome, folliculitis, furuncles, hidradenitis suppurativa, carbuncles, paronychial infections, rashes, erythrasma, impetigo, ecthyma, yeast skin infections, warts, molluscum contagiosum, trauma or injury to the skin, post-operative or post-surgical skin conditions, 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, skin ulcers, ischemic necrosis, miliaria, hyperhidrosis, moles, 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, chemical or thermal skin burns, scleroderma, aging skin, wrinkles, sun spots, necrotizing fasciitis, necrotizing myositis, gangrene, scarring, vitiligo,  chlamydia  infection, gonorrhea infection, hepatitis B, herpes, HIV/AIDS, human papillomavirus (HPV), genital warts, 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, genital cancer, cancer of the cervix, cancer of the vulva, cancer of the vagina, vaginal dryness, dyspareunia, anal and rectal disease, anal abscess/fistula, anal cancer, anal fissure, anal warts, Crohn's disease, hemorrhoids, anal itch, pruritus ani, fecal incontinence, constipation, polyps of the colon and rectum, a bacterial infection, a fungal infection, a yeast infection, a viral infection, a parasitic infection, wound, ulcer, and burn. 
     
     
         26 . A collapsed foam composition, comprising:
 a) a solid wax or a solid oil;   b) at least one liquid oil;   c) at least one foam stabilizing agent; and   d) a minocycline or a doxycycline or both;   wherein the composition is substantially water-free; and   wherein the minocycline or the doxycycline is stable for at least 3 weeks at 25° C. in the foamable pharmaceutical composition.