US 20060018937A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0018937 A1 Friedman et al. (43) Pub. Date: Jan. 26, 2006 (54) STEROID KIT AND FOAMABLE Oct. 25, 2002 (IL)................................................. 1524.86 COMPOSITION AND USES THEREOF (75) Inventors: Doron Friedman, Karmei Yosef (IL); Publication Classification Alex Besonov, Rehovet (IL); Dov Tamarkin, Maccabim (IL); Meir Eini, (51) Int. Cl. Ness Ziona (IL) A6IK 8/02 (2006.01) Correspondence Address: (52) U.S. Cl. .............................................................. 424/401 WILMER CUTLER PICKERING HALE AND DORR LLP (57) ABSTRACT 60 STATE STREET BOSTON, MA 02109 (US) A composition and therapeutic kit including an aeroSol packaging assembly including a container accommodating a (73) Assignee: Foamix Ltd. preSSurized product and an outlet capable of releasing a foamable composition, including a Steroid as a foam. The (21) Appl. No.: 11/114,410 preSSurized product includes a foamable composition including: a container accommodating a pressurized prod (22) Filed: Apr. 26, 2005 uct; and an outlet capable of releasing the pressurized Related U.S. Application Data product as a foam; wherein the pressurized product com O prises a foamable composition including: i. a steroid; ii. at (63) Continuation-in-part of application No. 10/911,367, least one organic carrier selected from the group consisting filed on Aug. 4, 2004. of hydrophobic Organic carrier, a polar solvent, an emol Continuation-in-part of application No. 10/532,618, lient and mixtures thereof, at a concentration of about 2% to filed as 371 of international application No. PCT/ about 50% by weight; iii. a surface-active agent, IV. about IB03/05527, filed on Oct. 24, 2003. 0.01% to about 5% by weight of at least OC polymeric additive Selected from the group consisting of a bioadhesive (60) Provisional application No. 60/492.385, filed on Aug. agent, a gelling agent, a film forming agent and a phase 4, 2003. Provisional application No. 60/429,546, filed change agent; v. water; and vi. liquefied or compressed gas on Nov. 29, 2002. propellant at a concentration of about 3% to about 25% by weight of the total composition. The composition further (30) Foreign Application Priority Data may include a therapeutically active foam adjuvant, Selected from the group consisting of a fatty alcohol, a fatty acid, a Oct. 24, 2003 (WO)............................ PCT/IB03/05527 hydroxyl fatty acid; and mixtures thereof. 90 AEROSOL VALVE G valvesTEM V32. WALWE CUP Y. triNER GASKET 2 Co OUTER GASKE 2- C - WALWE USG SPREG 3O 2. PTUE --> O Patent Application Publication Jan. 26, 2006 Sheet 1 of 2 US 2006/0018937 A1 Figure 1 AEROSOL VALVE G valve stEM V32. valve triNER GASKET 3 Co f OUTER GASKE 2- C - WAWE HOUSG SPREC 3O 2. OP TEBE r - O Patent Application Publication Jan. 26, 2006 Sheet 2 of 2 US 2006/0018937 A1 Figure 2 - microscopic pictures (x400, polarization Emulsion composition BV3 - no '. Aqueous composition BV6, including Crvstals are observed a polymeric agent and a surfactant - no Crystals are observed . (v. Aqueous composition BV4, $: Aqueous composition BV5, including one polymeric agent including two ploymeric agent (methocel) - crystals are observed (methocel+xanthan gum) - crystals are observed fr a commercial betamethasone Valerate 0.12% cream - Crystals are observed US 2006/OO18937 A1 Jan. 26, 2006 STEROID KIT AND FOAMABLE COMPOSITION both water and the occlusive agent; and wherein there is AND USES THEREOF enough occlusive agent to form an occlusive layer on the skin. CROSS REFERENCE TO RELATED APPLICATIONS 0006 A few dermatological foam products are available on the market. 0001. This application is a continuation-in-part applica tion of co-pending International Patent Application No. 0007 OluxTM Foam, produced by Connetics, Inc., con tains clobetasol propionate. Each gram of OluxTM Foam IB03/005527, designating the United States and filed on Oct. contains 0.5 mg clobetasol propionate, USP, in a thermo 24, 2003, which claims the benefit of priority under 35 labile foam, which consists of ethanol (60%), purified water, U.S.C. S.119(e) to U.S. Patent Application Ser. No. 60/492, propylene glycol, cetyl alcohol, Stearyl alcohol, polySorbate 546, filed on Nov. 29, 2002, both entitled “Cosmetic and 60, citric acid, and potassium citrate. It is dispensed from an Pharmaceutical Foam,” and which claims the benefit of aluminum can pressurized with a hydrocarbon propellant priority under 35 USC S119(a) to Israeli Patent Application. (propane/butane). Luxic" is another corticostroid foam No. 152486, filed Oct. 25, 2002, all of which are hereby medication, containing 1.2 mg betamethasone Valerate per incorporated in their entirety by reference. gram, in a vehicle, comprising ethanol (60.4%), purified 0002 This application is a continuation-in-part applica water, propylene glycol, cetyl alcohol, Stearyl alcohol, tion of co-pending U.S. patent application Ser. No. 10/911, polySorbate 60, citric acid, and potassium citrate, and pres 367, filed on Aug. 4, 2004, which claims the benefit of surized with a hydrocarbon propellant. Cortifoam TM, a 10 wt priority under 35 U.S.C. S119(e) to U.S. Patent Application % hydrocortisone acetate rectal foam, is produced by Ser. No. 60/492,385, filed on Aug. 4, 2003, both entitled Schwartz Pharma GmbH. Non medicinal ingredients of “Foam Carrier Containing Amphiphilic Copolymer Gelling Cortifoam TM include cetyl alcohol, ethoxylated Stearyl alco Agent” and both hereby incorporated in their entirety by hol, methylparaben, polyoxyethylene-10 Stearyl ether, pro reference. pylene glycol, propylparaben, triethanolamine, water, and inert propellants, isobutene, and propane. BACKGROUND OF THE INVENTION 0008 Thus, low alcohol content foam compositions for 0.003 Steroids are available in topical dosage form. Com topical treatment containing higher concentrations of oils are positions containing Steroids for topical treatment of derma not currently commercially available. Foam compositions tologic disorders are available primarily in cream, lotion gel that are robust and Suitable for inclusion of a wide range of and ointment forms. While Semi-Solid compositions, Such as active ingredients are desired. creams, lotions, gels and ointments are commonly used by consumers, new forms are desirable, in order to achieve SUMMARY OF THE INVENTION better control of the application, while maintaining or bestowing the skin beneficial properties of Such products. 0009. The present invention provides a therapeutic kit Thus, the development of new compositions having break including a foamable Steroid composition. The kit includes able foam consistency when released from a container and an aerosol packaging assembly having a container accom liquid properties when applied onto the skin are advanta modating a pressurized product and an outlet capable of geous. releasing the pressurized product as a foam. 0004 Foams and, in particular, foam emulsions are com 0010. The therapeutic kit includes an aerosol packaging plicated Systems which do not form under all circumstances. assembly including (a) a container accommodating a pres Slight Shifts in foam emulsion composition, Such as by the Surized product and (b) outlet capable of releasing the addition of active ingredients, may destabilize the foamable preSSurized product as a foam; wherein the pressurized composition during Storage, and/or impair the quality of the product contains a foamable composition including: (i) a foam that is produced upon release from the aerosol con Steroid; (ii) at least one organic carrier Selected from the tainer. group consisting of a hydrophobic organic carrier, an organic polar Solvent, an emollient and mixtures thereof, at 0005 U.S. Pat. No. 6,126,920 discloses treatment of a concentration of about 2% to about 50% by weight; (iii) a various skin diseases, and in particular, Scalp psoriasis, using surface-active agent; (iv) about 0.01% to about 5% by a foamable pharmaceutical composition containing a corti weight of at least one polymeric additive Selected from the costeroid active Substance, an aliphatic alcohol, water, a group consisting of a bioadhesive agent, a gelling agent, a fatty alcohol, a Surface-active agent, a propellant and a film forming agent and a phase change agent, (v) water; and buffering agent. The foamable composition contains 40-90% (vi) liquefied or compressed gas propellant at a concentra w/w composition of an aliphatic alcohol. U.S. Pat. No. tion of about 3% to about 25% by weight of the total 6,126,920 is typical of many compositions that use aliphatic composition. alcohols in the foam composition. The alcohol promotes fast drying and thereby attempts to address the Sticky feeling left 0011. According to one or more embodiments, the foam by many topical formulations after application; however, able composition is Substantially alcohol-free, i.e., free of alcohols, and in particular the methyl, ethyl and isopropyl Short chain alcohols. Short chain alcohols, having up to 5 alcohols preferred in the 920 patent, are defatting agents carbon atoms in their carbon chain Skeleton and one and may cause skin to become dry and cracked. U.S. Pat. hydroxyl group, Such as ethanol, propanol, isopropanol, No. 6,730,288 teaches a pharmaceutical foam composition butanol, iso-butanol, t-butanol and pentanol, are considered including (a) an active ingredient; (b) an occlusive agent; (c) less desirable Solvents or polar Solvents due to their skin an aqueous Solvent; and (d) an organic