Foamable vehicle and pharmaceutical compositions thereof

Abstract

A hygroscopic pharmaceutical composition includes at least one hygroscopic substance at a concentration sufficient to provide an Aw value of at least 0.9 and an antiinfective agent. A foamble pharmaceutical carrier includes about 50% to about 98% of a polar solvent selected from the group consisting of a polyol and PEG; 0% to about 48% of a secondary polar solvent; about 0.2% to about 5% by weight of a surface-active agent; about 0.01% to about 5% by weight of at least one polymeric agent; and a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition.

1 . A method of treating a disorder of the skin, body cavity, or mucosal surface, the method comprising applying a therapeutically effective amount of a foamable hygroscopic pharmaceutical composition to the skin, body cavity, or mucosal surface of a patient in need thereof, wherein the foamable hygroscopic pharmaceutical composition comprises:
 i) a carrier composition comprising:
 a) a therapeutically effective amount of one or more active agents; 
 b) about 50% to about 98% by weight of the carrier composition of a polar solvent selected from the group consisting of a polyol, a polyethylene glycol (PEG), or a mixture thereof; 
 c) 0% to about 48% by weight of the carrier composition of a secondary polar solvent; 
 d) about 0.01% to about 5% by weight of the carrier composition of a gelling agent; and 
 e) 0% to about 25% by weight of the carrier composition of water; and 
   ii) a liquefied or compressed gas propellant;   
       wherein the foamable hygroscopic pharmaceutical composition forms a breakable foam upon release from a pressurized container; wherein the breakable foam does not immediately collapse upon exposure to skin temperature; and wherein the breakable foam breaks under shear force. 
     
     
         2 . The method of  claim 1 , wherein the gelling agent comprises a cellulose polymer. 
     
     
         3 . The method of  claim 1 , wherein the polar solvent is a PEG, and the PEG is selected from the group consisting of PEG 200, PEG 300, PEG 400, PEG 600, PEG 1000, PEG 4000, PEG 6000, and PEG 8000. 
     
     
         4 . The method of  claim 1 , wherein the foamable hygroscopic pharmaceutical composition does not contain a surface-active agent. 
     
     
         5 . The method of  claim 1 , wherein the polar solvent is a polyol, and the polyol comprises at least one of glycerin, butane-1,2,3-triol, butane-1,2,4-triol, hexane-1,2,6-triol, propylene glycol, butanediol, butenediol, butynediol, pentanediol, hexanediol, octanediol, neopentyl glycol, 2-methyl-1,3-propanediol, diethylene glycol, triethylene glycol, tetraethylene glycol, dipropylene glycol, and dibutylene glycol, or a mixture of at least two polyols. 
     
     
         6 . The method of  claim 1 , wherein the polar solvent comprises a mixture of at least one polyol and at least one PEG. 
     
     
         7 . The method of  claim 1 , wherein the foamble hygroscopic pharmaceutical composition is substantially non-aqueous. 
     
     
         8 . The method of  claim 1 , wherein the foamble hygroscopic pharmaceutical composition is substantially free of short-chain alcohols. 
     
     
         9 . The method of  claim 1 , wherein the foamble hygroscopic pharmaceutical composition forms a stable foam at normal skin temperature for at least about 240 seconds upon release from the pressurized container. 
     
     
         10 . The method of  claim 1 , wherein the carrier composition further comprises about 0.2% to about 5% by weight of the carrier composition of a surface-active agent. 
     
     
         11 . The method of  claim 10 , wherein the surface-active agent comprises a non-ionic surfactant. 
     
     
         12 . The method of  claim 10 , wherein the surface-active agent comprises at least one non-ionic surfactant and at least one ionic surfactant. 
     
     
         13 . The method of  claim 10 , wherein the carrier composition further comprises a hygroscopic substance selected from the group consisting of monosaccharides, disaccharides, oligosaccharides, sugar alcohols, honey, and a PEG containing surfactant; and wherein the carrier composition has an Aw value of less than 0.9. 
     
     
         14 . The method of  claim 1 , wherein the disorder is selected from the group consisting of 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, fungal infection of nail and nail bed, infection of mucosa, 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, and 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; and wherein the active agent is suitable for treating the disorder. 
     
     
         15 . The method of  claim 1 , wherein the active agent is selected from the group consisting of alclometasone dipropionate, amcinafel, amcinafide, amcinonide, beclomethasone, beclomethasone dipropionate, betamethsone, betamethasone benzoate, betamethasone dexamethasone-phosphate, dipropionate, betamethasone valerate, budesonide, chloroprednisone, chlorprednisone acetate, clescinolone, clobetasol, clobetasol propionate, clobetasol valerate, clobetasone, clobetasone butyrate, clocortelone, cortisone, cortodoxone, craposone butyrate, desonide, desoxymethasone, dexamethasone, desoxycorticosterone acetate, dichlorisone, diflorasone diacetate, diflucortolone valerate, difluorosone diacetate, diflurprednate, fluadrenolone, flucetonide, flucloronide, fluclorolone acetonide, flucortine butylesters, fludroxycortide, fludrocortisone, flumethasone, flumethasone pivalate, flumethasone pivalate, flunisolide, fluocinolone, fluocinolone acetonide, fluocinonide, fluocortin butyl, fluocortolone, fluorometholone, fluosinolone acetonide, fluperolone, fluprednidene acetate, fluprednisolone hydrocortamate, fluradrenolone, fluradrenolone acetonide, flurandrenolone, fluticasone, halcinonide, halobetasol, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone cyclopentylpropionate, hydrocortisone valerate, hydroxyltriamcinolone, medrysone, meprednisone, alpha-methyl dexamethasone, methylprednisolone, methylprednisolone acetate, mometasone fiaroate, paramethasone, prednisolone, prednisone, pregnenolone, progesterone, spironolactone, triameinolone, triameinolone acetonide, and salts thereof. 
     
     
         16 . The method of  claim 1 , wherein the active agent is an anti-infective agent and the anti-infective agent is selected from one or more of an antibiotic agent, an antibacterial agent, an antifungal agent, an agent that controls yeast, an antiviral agent, and an antiparasitic agent. 
     
     
         17 . The method of  claim 16 , wherein the anti-infective agent is an antifungal agent and the antifungal agent is selected from the group consisting of a polyene, natamycin, nystatin; an allylamine, naflifine, terbinafine; an imidazole, bifonazole, clotrimazole, econazole, fenticonazole, ketocanazole, miconazole, oxiconazole; a diazole, a triazoles, fluconazole, itraconazole, terconazole, tolnafiate, ciclopirox, undecylenic acid, sulbentine, griseofulvin, Amphotericin B, flucytosine (5FC), a morpholine compound, amorolfine, and salts thereof. 
     
     
         18 . The method of  claim 16 , wherein the anti-infective agent is an antibacterial agent and the antibacterial agent is selected from the group consisting of a beta-lactam antibiotic, an aminoglycoside, an ansa-type antibiotic, an anthraquinone, an azole, metronidazole, an antibiotic glycopeptide, a macrolide, erythromycin, clindamycin, an antibiotic nucleoside, an antibiotic peptide, polymyxin B, an antibiotic polyene, an antibiotic polyether, an antibiotic quinolone, an antibiotic steroid, fucidic acid, mupirocin, chioramphenicol, a sulfonamide, tetracycline, an antibiotic metal, silver, copper, zinc, mercury, tin, lead, bismuth, cadmium, chromium, an oxidizing agent, iodine, iodate, a periodate, a hypochlorite, a permanganate, a substance that release free radicals and/or active oxygen, a cationic antimicrobial agent, a quaternary ammonium compound, a biguanide, chlorohexidine, a triguanide, a bisbiguanide, a polymeric biguanide, a naturally occurring antibiotic compound, and salts thereof. 
     
     
         19 . The method of  claim 16 , wherein the active agent comprises a combination of (1) a corticosteroid; and (2) and active agent selected from the group consisting of an anti-infective agent, an antifungal agent, an antimicrobial agent, an antiviral agent, an anti-acne agent, a retinoid, a vitamin D3, calcipotriol, and antipsoriasis agent, a keratolytic agent, an anti-proliferative agent, an anti-cancer agent, a non-steroidal anti-inflammatory agent, an immunomodulator, an immunosuppressant, and an anti-rosacea agent. 
     
     
         20 . The method of  claim 1 , wherein the active agent comprises a combination of (1) a keratolytic agent; and (2) and active agent selected from the group consisting of a corticosteroid, an anti-infective agent, an antifungal agent, an antimicrobial agent, an antiviral agent, an anti-acne agent, a retinoid, a vitamin D3, calcipotriol, and antipsoriasis agent, an anti-proliferative agent, an anti-cancer agent, a non-steroidal anti-inflammatory agent, an immunomodulator, an immunosuppressant, and an anti-rosacea agent. 
     
     
         21 . The method of  claim 17 , wherein the active agent is terbinafine and the disorder is a fungal infection, a yeast infection, or both.