OIL-BASED FOAMABLE CARRIERS AND FORMULATIONS

• US 20110268665A1
• Filed: 10/06/2009
• Published: 11/03/2011
• Est. Priority Date: 12/07/2007
• Status: Active Grant

• Current Assignee: Journey Medical Corp. (Fortress Biotech, Inc.)
• Original Assignee: Foamix Ltd. (VYNE Therapeutics, Inc.)
• Inventors: Hazot, Yohan, Schuz, David, Tamarkin, Dov, Gazal, Elana
• Granted Patent: US 8,518,376 B2
• Time in Patent Office: Days
• US Class Current: 424/43
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 17/12 Keratolytics, e.g. wart or anti-corn preparations
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

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.

Claims

1. A waterless foamable pharmaceutical composition, comprising a foamable carrier and at least one liquefied or compressed gas propellant wherein the foamable carrier consists essentially of:

about 60% to about 98% by weight of at least one liquid oil; and

about 2% to about 40% by weight of a surfactant, wherein the surfactant comprises at least a glyceride; and

optionally an additive selected from the group consisting of a foam adjuvant, a polymer stabilizer, a thickener, and mixtures thereof;

wherein the ingredients are compatible with a minocycline antibiotic; and

wherein the foamable carrier is substantially a single phase, is in a compatible canister and wherein upon dispensing the foamable carrier composition forms a breakable foam that is thermally stable, yet breaks easily upon application of shear force.

2. The waterless foamable pharmaceutical composition of claim 1, wherein the average bubble size of the foam is less than about 200 microns.

3. The waterless foamable pharmaceutical composition of claim 1, wherein the glyceride is a monoglyceride, diglyceride, or a triglyceride.

4. The waterless foamable pharmaceutical composition of claim 3, wherein the side chain of the monoglyceride, diglyceride, or triglyceride is a C8-C24 saturated hydrocarbon.

5. The waterless foamable pharmaceutical composition of claim 3, wherein the side chain of the monoglyceride is a C8-C24 saturated hydrocarbon and the side chain of the diglyceride or triglyceride is a C8-C14 saturated hydrocarbon.

6. The waterless foamable pharmaceutical composition of claim 1, wherein the surfactant further comprises a surfactant selected from the group consisting of polysorbate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan monooleate, a polyoxyethylene fatty acid ester, polyoxyethylene (8) stearate (Myrj 45), polyoxyethylene (20) stearate (Myrj 49), polyoxyethylene (40) stearate (Myrj 52), and polyoxyethylene (100) stearate (Myrj 59), a polyoxyethylene alkyl ether, polyoxyethylene cetyl ether, a steareth such as steareth 2, steareth 21 (Brij 721), polyoxyethylene (23) cetyl ether (Brij 38), polyoxyethylene (2) cetyl ether (Brij 52), polyoxyethylene (10) cetyl ether (Brij 56), a sucrose ester, a partial ester of sorbitol and its anhydrides, sorbitan monolaurate, isoceteth-20 and mono-, and di- and tri-esters of sucrose with fatty acids.

7. The waterless foamable pharmaceutical composition of claim 4, wherein the side chain of the monoglyceride contains at least 8 carbon atoms.

8. The waterless foamable pharmaceutical composition of claim 4, wherein the monoglyceride is glyceryl monostearate.

9. The waterless foamable pharmaceutical composition of claim 4, wherein the monoglyceride is a solid.

10. The waterless foamable pharmaceutical composition of claim 1, wherein at least one liquid oil comprises mineral oil.

11. The waterless foamable pharmaceutical composition of claim 1, wherein at least one oil is selected from the group consisting of mineral oil, MCT oil, liquid paraffin, vegetable oil, essential oil, organic oil, lipid, or a mixture of two or more thereof.

12. The waterless foamable pharmaceutical composition of claim 10, wherein the oil is a mixture of light mineral oil and heavy mineral oil.

13. The waterless foamable pharmaceutical composition of claim 12, wherein the weight ratio of the light mineral oil to the heavy mineral oil ranges from about 1:

1 to about 1;

2.

14. The waterless foamable pharmaceutical composition of claim 1, further comprising an active agent.

15. The waterless foamable pharmaceutical composition according to claim 14, wherein the active agent is soluble in the liquid oil, the monoglyceride or the carrier.

16. The waterless foamable pharmaceutical composition according to claim 14, wherein the foamable carrier including the active agent is a substantially homogenous suspension.

17. The waterless foamable pharmaceutical composition of claim 14, wherein the active agent is selected from the group consisting of an acaricides, 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 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 mixtures thereof.

18. The waterless foamable pharmaceutical composition of claim 14, wherein the active agent is a tetracycline antibiotic agent.

19. The waterless foamable pharmaceutical composition of claim 18, wherein the tetracycline antibiotic agent comprises minocycline or doxycycline.

20. The waterless foamable pharmaceutical composition of claim 14, wherein the 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 mixtures thereof.

21. The waterless foamable pharmaceutical composition of claim 1, wherein the composition further comprises one or more additional components selected from the group consisting of anti-perspirants, anti-static agents, buffering agents, anti-oxidants/free radical scavengers, bulking agents, chelating agents, cleansers, colorants, conditioners, deodorants, diluents, dyes, fragrances, hair conditioners, humectants, modulating agents, pearlescent aids, perfuming agents, permeation enhancers, pH-adjusting agents, occlusive agents, preservatives, protectants, skin penetration enhancers, softeners, solubilizers, sunscreens, sun blocking agents, sunless tanning agents, viscosity modifiers, and vitamins.

29. A method of delivering an active agent to a patient in need of treatment, the method comprising administering the waterless foamable pharmaceutical composition of claim 14 to a skin surface, a mucosal surface, the eye, or a body cavity.

30. The method of claim 29, wherein a pharmaceutically effective amount of the composition is administered to the skin or mucosal surface.

32. A method according to claim 29, wherein the pharmaceutical composition comprises a combination of at least two active agents.

33. A method according to claim 29, wherein a pharmaceutically effective amount of the composition is administered to a body cavity, wherein the cavity is selected from the group consisting of the nose, the mouth, the ear canal, the respiratory system cavities, the vagina and the rectum.

42. The method of claim 29 for treating a disorder selected from the group consisting of skin, body cavity, mucosal membrane, ear channel, eye, nasal, oral, respiratory, vaginal, rectal and urethra disorders, or for treating a disorder 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, 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, 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, post-surgical adhesions, acne, and rosacea.

45. The waterless foamable pharmaceutical composition of claim 10, wherein the oil is a mixture of a vegetable oil, a mineral oil, a silicone oil, and a castor oil.

46. The waterless foamable pharmaceutical composition of claim 10, wherein the oil contains a wax.

22. A waterless foamable pharmaceutical composition, comprising a foamable carrier and at least one liquefied or compressed gas propellant wherein the foamable carrier comprises:

about 60% to about 98% by weight of at least one liquid oil;

about 2% to about 40% by weight of a surfactant, wherein the surfactant comprises at least a glyceride; and

an additive selected from the group consisting of a foam adjuvant and a polymer stabilizer;

wherein the foamable carrier is substantially a single phase and wherein upon dispensing the foamable carrier composition forms a breakable foam that is thermally stable, yet breaks easily upon application of shear force.

28. The waterless foamable pharmaceutical composition of claim 22, wherein the additive comprises a foam adjuvant, which is selected from the group consisting of a fatty alcohol, a fatty acid and a hydroxyl fatty acid.

31. A method of delivering an active agent to a patient in need of treatment, the method comprising administering the waterless foamable pharmaceutical composition of claim 22 to a skin surface, a mucosal surface, an eye surface, or a body cavity.

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