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WO2006138035A1 - Vehicule pour l'administration d'agents pharmaceutiques solubles lipidiques topiques - Google Patents

Vehicule pour l'administration d'agents pharmaceutiques solubles lipidiques topiques Download PDF

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Publication number
WO2006138035A1
WO2006138035A1 PCT/US2006/020300 US2006020300W WO2006138035A1 WO 2006138035 A1 WO2006138035 A1 WO 2006138035A1 US 2006020300 W US2006020300 W US 2006020300W WO 2006138035 A1 WO2006138035 A1 WO 2006138035A1
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WIPO (PCT)
Prior art keywords
agents
oil
lipid soluble
pharmaceutical agent
soluble pharmaceutical
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2006/020300
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English (en)
Inventor
Paal Christian Klykken
Linda S. Nartker
Victor Albert Raul
Virginie Caprasse
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dow Silicones Corp
Original Assignee
Dow Corning Corp
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Filing date
Publication date
Application filed by Dow Corning Corp filed Critical Dow Corning Corp
Publication of WO2006138035A1 publication Critical patent/WO2006138035A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels

Definitions

  • This invention generally relates to a substantially anhydrous composition for topical delivery of a lipid soluble pharmaceutical agent.
  • the invention also generally relates to a method of delivering the pharmaceutical agent to a substrate.
  • compositions for the topical delivery of lipid soluble pharmaceutical agents are known in the art.
  • compositions containing lipophilic drugs in petrolatum base ointments are known.
  • These petrolatum-based compositions often contain a surfactant or propylene glycol to solubilize the drug and modulate drug release and/or skin permeation.
  • Petrolatum-based vehicles provide simple vehicles and provide chemical drug stability.
  • compositions containing water for the topical delivery of lipid soluble pharmaceutical agents are also known in the art.
  • oil in water emulsions containing lipophilic drugs are known.
  • compositions of this invention comprise a substantially anhydrous mixture containing a silicone elastomer, a solvent for the silicone elastomer, a surfactant and a lipid soluble pharmaceutical agent.
  • the method of the invention comprises mixing the solvent, the silicone elastomer, the surfactant and the lipid soluble pharmaceutical agent and applying the mixture to the substrate to which the pharmaceutical agent is to be released.
  • the present invention includes a composition comprising a substantially anhydrous mixture of a silicone elastomer, a solvent for the silicone elastomer, a surfactant and a lipid soluble pharmaceutical agent.
  • the present invention also includes a method of delivering the lipid soluble pharmaceutical agent to a substrate for a variety of applications including transdermal, pharmaceutical, veterinary, and oral health care uses.
  • substantially anhydrous denotes that water is not added to the composition as a component of the invention, but some residual water may be present in minor amounts in one of the other components added to the composition.
  • Silicone elastomers are known in the art. These are described, for example, in United States Patent No. 4,882,377 (issued November 21, 1989), United States Patent No. 5,654,362 (issued August 5, 1997), United States Patent No. 5,994,459 (issued November 30, 1999), United States Patent No. 6,015,858 (issued January 18, 2004), Unite States Patent No. 6,351,540, United States Patent No. 6,538,061, United States Patent No. 6,444,745, United States Patent No.
  • silicone elastomers are also commercially available from a variety of sources such as Dow Corning Corporation. These include Dow Corning® Elastomer 10 and 9041.
  • the silicone elastomers are present in the composition of the invention in an amount of 0.1 to 75 wt. %, alternatively about 1 to 40 wt. %. Mixtures of silicone elastomers can also be used.
  • the silicone elastomers are prepared by a crosslinking reaction between (A) ⁇ Si-H containing polysiloxanes and (B) an alpha, omega- diene in the presence of a platinum catalyst and (C) a low molecular weight linear or cyclic polysiloxane as described in US Patent No. 5,654,362.
  • the elastomers can be swollen with a low molecular weight polysiloxane under a shear force.
  • the ⁇ Si-H containing polysiloxane (A) is represented by compounds of the formula R 3 Si0(R' 2 Si0) a (R"HSi0) b SiR 3 designated herein as type A 1 and compounds of the formula HR 2 Si0(R' 2 Si0) c SiR 2 H or formula HR 2 Si0(R 2 Si0) a (R"HSi0) b SiR 2 H designated herein as type A 2 .
  • R, R 1 , and R are alkyl groups with 1-6 carbon atoms; a is 0-250; b is 1-250; and c is 0-250.
  • the molar ratio of compounds A 2 :A ! is generally 0-20, alternatively 0-5.
  • suitable alpha, omega-dienes for use herein are 1,4-pentadiene; 1,5-hexadiene; 1,6-heptadiene; 1,7-octadiene; 1,8-nonadiene; 1,9- decadiene; 1,11-dodecadiene; 1,13-tetradecadiene; and 1,19-eicosadiene.
  • the addition and crosslinking reaction requires a catalyst to effect the reaction between the ⁇ SiH containing polysiloxane and the alpha, omega-diene.
  • Suitable catalysts are Group VIII transition metals, i.e., the noble metals. Such noble metal catalysts are described in US Patent 3,923,705, incorporated herein by reference to show platinum catalysts.
  • One preferred platinum catalyst is Karstedt's catalyst, which is described in Karstedt's US Patents 3,715,334 and 3,814,730, incorporated herein by reference.
  • Karstedt's catalyst is a platinum divinyl tetramethyl disiloxane complex typically containing about one weight percent of platinum in a solvent such as toluene.
  • Another preferred platinum catalyst is a reaction product of chloroplatinic acid and an organosilicon compound containing terminal aliphatic unsaturation. It is described in US Patent 3,419,593, incorporated herein by reference.
  • the noble metal catalysts are used in amounts from 0.00001-0.5 parts per 100 weight parts of the ⁇ SiH containing polysiloxane, preferably 0.00001-0.02 parts, most preferably 0.00001-0.002 parts.
  • the solvent used herein may comprise a solvent for the silicone elastomer described above.
  • the solvent when combined with the elastomer, serves to suspend and swell the elastomer to provide an elastic, three- dimensional gel network or matrix.
  • the solvent for the polymer is liquid under ambient conditions and preferably has a low viscosity to provide for improved spreading on the skin.
  • the solvent is a low molecular weight silicone oil.
  • the phrase low molecular weight silicone oil is intended to include (i) low molecular weight linear and cyclic volatile methyl siloxanes, (ii) low molecular weight linear and cyclic volatile and non- volatile alkyl and aryl siloxanes, and (iii) low molecular weight linear and cyclic functional siloxanes.
  • VMS low molecular weight linear and/or cyclic volatile methyl siloxanes
  • volatile as used herein refers to materials which exhibit a vapor pressure of more than about 0.2 mm Hg at 25° C. at one atmosphere and/or to materials that have a boiling point at one atmosphere of less than about 300° C.
  • VMS compounds correspond to the average unit formula (CH 3 ) a Si0( 4-a ) /2 in which a has an average value of two to three.
  • the compounds contain siloxane units joined by ⁇ Si-O- Si ⁇ bonds.
  • Representative units are monofunctional "M” units (CHs) 3 SiO 1Z2 and difunctional "D” units (CH 3 ) 2 Si0 2/2 .
  • the presence of trifunctional "T” units CH 3 SiO 372 results in the formation of branched linear or cyclic volatile methyl siloxanes.
  • the presence of tetrafunctional "Q" units SiO 4/2 results in the formation of branched linear or cyclic volatile methyl siloxanes.
  • Linear VMS have the formula (CH 3 ) 3 SiO ⁇ (CH 3 ) 2 SiO ⁇ y Si(CH 3 ) 3 .
  • the value of y is 0-
  • Cyclic VMS have the formula ⁇ (CH 3 ) 2 Si0 ⁇ z .
  • the value of z is 3-6. These volatile methyl siloxane often have boiling points less than about 250 0 C and viscosities of about 0.65-5.0 centistokes (mm ⁇ /s).
  • Representative linear volatile methyl siloxanes (I) are hexamethyldisiloxane (MM) with a boiling point of 100 0 C, viscosity of 0.65 mm ⁇ /s, and formula Me3SiOSiMe3; octamethyltrisiloxane (MDM) with a boiling point of 152 °C, viscosity of 1.04 mm ⁇ /s, and formula Me3SiOMe2SiOSiMe3; decamethyltetrasiloxane (MD2M) with a boiling point of
  • Representative cyclic volatile methyl siloxanes (II) are hexamethylcyclotrisiloxane (D3) a solid with a boiling point of 134 °C and formula ⁇ (M ⁇ 2)SiO ⁇ 3; octamethylcyclotetrasiloxane (D4) with a boiling point of 176 °C, viscosity of 2.3 mm ⁇ /s, and formula ⁇ (Me2)SiO ⁇ 4; decamethylcyclopentasiloxane (D5) with a boiling point of 210 °C, viscosity of 3.87 mnvVs, and formula ⁇ (Me2)SiO ⁇ 5; and dodecamethylcyclohexasiloxane
  • Representative branched volatile methyl siloxanes (III) and (IV) are heptamethyl-3- ⁇ (trimethylsilyl)oxy ⁇ trisiloxane (M3T) with a boiling point of 192 °C, viscosity of 1.57 mm ⁇ /s, and formula ⁇ 9!!3003Si 4 ; hexamethyl-3,3,bis ⁇ (trimethylsilyl)oxy ⁇ trisiloxane (M4Q) with a boiling point of 222 °C, viscosity of 2.86 mm ⁇ /s, and formula Ci2H36 ⁇ 4 Si5; and pentamethyl ⁇ (trimethylsilyl)oxy ⁇ cyclotrisiloxane (MD3) with the formula C 8 H 24 O 4 Si 4 .
  • M3T heptamethyl-3- ⁇ (trimethylsilyl)oxy ⁇ trisiloxane
  • M4Q hexamethyl-3,3,bis ⁇ (trimethylsilyl)oxy ⁇ trisiloxan
  • the invention also includes using low molecular weight linear and cyclic volatile and non-volatile alkyl and aryl siloxanes.
  • Representative linear polysiloxanes are compounds of the formula R 3 Si0(R 2 Si0) y SiR 3
  • representative cyclic polysiloxanes are compounds of the formula (R 2 SiO) 2 .
  • R is an alkyl group of 1-6 carbon atoms, or an aryl group such as phenyl.
  • the value of y is 0-80, preferably 0-20.
  • the value of z is 0-9, preferably 4-6.
  • solvents can swell the silicone elastomer.
  • a single solvent or a mixture of solvents may be used.
  • solvent we mean (i) organic compounds, (ii) compounds containing a silicon atom, (iii) mixtures of organic compounds, (iv) mixtures of compounds containing a silicon atom, or (v) mixtures of organic compounds and compounds containing a silicon atom.
  • the organic compounds are aromatic hydrocarbons, aliphatic hydrocarbons, alcohols, aldehydes, ketones, amines, esters, ethers, glycols, glycol ethers, alkyl halides, or aromatic halides.
  • alcohols such as methanol, ethanol, 1-propanol, cyclohexanol, benzyl alcohol, 2-octanol, ethylene glycol, propylene glycol, and glycerol
  • aliphatic hydrocarbons such as pentane, cyclohexane, heptane, VM &P solvent, and mineral spirits
  • alkyl halides such as chloroform, carbon tetrachloride, perchloroethylene, ethyl chloride, and chlorobenzene
  • amines such as isopropylamine, cyclohexylamine, ethanolamine, and diethanolamine
  • aromatic hydrocarbons such as benzene, toluene, ethylbenzene, and xylene
  • esters such as ethyl acetate, isopropyl acetate, ethyl acetoacetate, amyl acetate, isobutyl is
  • miscellaneous organic solvents can also be used, such as acetonitrile, nitromethane, dimethylformamide, propylene oxide, trioctyl phosphate, butyrolactone, furfural, pine oil, turpentine, and m-creosol.
  • Still other solvents include volatile flavoring agents such as oil of wintergreen; peppermint oil; spearmint oil; menthol; vanilla; cinnamon oil; clove oil; bay oil; anise oil; eucalyptus oil; thyme oil; cedar leaf oil; oil of nutmeg; oil of sage; cassia oil; cocoa; licorice; high fructose corn syrup; citrus oils such as lemon, range, lime, and grapefruit; fruit essences such as apple, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, and apricot; and other useful flavoring agents including aldehydes and esters such as cinnamyl acetate, cinnamaldehyde, eugenyl formate, p- methylanisole, acetaldehyde, benzaldehyde, anisic aldehyde, citral, neral, decanal, vanillin, tolyl aldehyde, 2,6-d
  • solvent can also include volatile fragrances such as natural products and perfume oils.
  • Some representative natural products and perfume oils are ambergris, benzoin, civet, clove, leaf oil, jasmine, mate, mimosa, musk, myrrh, orris, sandalwood oil, and vetivert oil; aroma chemicals such as amyl salicylate, amyl cinnamic aldehyde, benzyl acetate, citronellol, coumarin, geraniol, isobornyl acetate, ambrette, and terpinyl acetate; and the various classic family perfume oils such as the floral bouquet family, the oriental family, the chypre family, the woody family, the citrus family, the canoe family, the leather family, the spice family, and the herbal family.
  • the solvent is generally used in the invention in an amount of about 1 to 99 wt. %, alternatively 5 to 70 wt. %. Mixtures of solvents can also be used.
  • the composition of the present invention also includes a surfactant.
  • the surfactant helps disperse, suspend and/or solubilize the lipid soluble pharmaceutical agent and other ingredients in the form of micelles, vesicles, liquid crystals, lamellar phases, and other thermodynamically stable associative phases or structures. Further, the surfactant provides the ability to coat the substrate and provides additional sensory benefits.
  • Known or conventional surfactants can be used in the composition, provided that the selected surfactant is chemically and physically compatible with essential components of the composition and provides the desired dispersion characteristics.
  • surfactants include those selected from the group consisting of anionic surfactants, nonionic surfactants, amphoteric surfactants, non- lathering surfactants, emulsifiers and mixtures thereof.
  • anionic surfactants include those selected from the group consisting of anionic surfactants, nonionic surfactants, amphoteric surfactants, non- lathering surfactants, emulsifiers and mixtures thereof.
  • Non-limiting examples of surfactants useful in the compositions of the present invention are disclosed in U.S. Pat. No. 6,280,757, to McAtee et al., issued Aug. 28, 2001 which is included by reference herein.
  • anionic surfactants useful in the compositions of the present invention are disclosed in McCutcheon's, Detergents and Emulsifiers, North American edition (1986), published by allured Publishing Corporation; McCutcheon's, Functional Materials, North American Edition (1992); and U.S. Pat. No. 3,929,678, to Laughlin et al., issued Dec. 30, 1975, which is incorporated by reference herein. These include those selected from the group consisting of sarcosinates, sulfates, isethionates, taurates, phosphates, lactylates, glutamates, and mixtures thereof.
  • fatty acid soaps i.e., alkali metal salts, e.g., sodium or potassium salts
  • fatty acid soaps typically having from a fatty acid having about 8 to about 24 carbon atoms, preferably from about 10 to about 20 carbon atoms.
  • These fatty acids used in making the soaps can be obtained from natural sources such as, for instance, plant or animal-derived glycerides (e.g., palm oil, coconut oil, soybean oil, castor oil, tallow, lard, etc.)
  • the fatty acids can also be synthetically prepared. Soaps and their preparation are described in detail in U.S. Pat. No. 4,557,853.
  • anionic materials include phosphates such as monoalkyl, dialkyl, and trialkylphosphate salts.
  • anionic lathering surfactants useful herein include those selected from the group consisting of sodium lauryl sulfate, ammonium lauryl sulfate, ammonium laureth sulfate, sodium laureth sulfate, sodium trideceth sulfate, ammonium cetyl sulfate, sodium cetyl sulfate, ammonium cocoyl isethionate, sodium lauroyl isethionate, sodium lauroyl lactylate, triethanolamine lauroyl lactylate, sodium caproyl lactylate, sodium lauroyl sarcosinate, sodium myristoyl sarcosinate, sodium cocoyl sarcosinate, sodium lauroyl methyl taurate, sodium cocoyl methyl taurate, sodium lauroyl glutamate, sodium myristoyl gluta
  • Non-limiting examples of nonionic surfactants for use in the compositions of the present invention are disclosed in McCutcheon's, Detergents and Emulsifiers, North American edition (1986), published by allured Publishing Corporation; and McCutcheon's, Functional Materials, North American Edition (1992). These include those selected from the group consisting of alkyl glucosides, alkyl polyglucosides, polyhydroxy fatty acid amides, alkoxylated fatty acid esters, sucrose esters, amine oxides, and mixtures thereof.
  • compositions of the present invention include those selected form the group consisting of C 8 -C 14 glucose amides, C 8 -C 14 alkyl polyglucosides, sucrose cocoate, sucrose laurate, lauramine oxide, cocoamine oxide and mixtures thereof.
  • amphoteric lathering surfactants can be used in the compositions of the present invention.
  • Particularly useful are those which are broadly described as derivatives of aliphatic secondary and tertiary amines, preferably wherein the nitrogen is in a cationic state, in which the aliphatic radicals can be straight or branched chain and wherein one of the radicals contains an ionizable water solubilizing group, e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate.
  • amphoteric surfactants useful in the compositions of the present invention are disclosed in McCutcheon's, Detergents and Emulsifiers, North American edition (1986), published by allured Publishing Corporation; and McCutcheon's, Functional Materials, North American Edition (1992).
  • Non-limiting examples zwitterionic surfactants are those selected from the group consisting of betaines, sultaines, hydroxysultaines, alkyliminoacetates, iminodialkanoates, aminoalkanoates, and mixtures thereof. [0037] A wide variety of non-lathering surfactants are useful herein.
  • Nonlimiting examples of these non-lathering compositions are: polyethylene glycol 20 sorbitan monolaurate (Polysorbate 20), polyethylene glycol 5 soya sterol, Steareth-20, Ceteareth-20, PPG-2 methyl glucose ether distearate, Ceteth-10, Polysorbate 80, cetyl phosphate, potassium cetyl phosphate, diethanolamine cetyl phosphate, Polysorbate 60, glyceryl stearate, PEG-100 stearate, polyoxyethylene 20 sorbitan trioleate (Polysorbate 85), sorbitan monolaurate, polyoxyethylene 4 lauryl ether sodium stearate, polyglyceryW isostearate, hexyl laurate, steareth-20, ceteareth-20, PPG-2 methyl glucose ether distearate, ceteth-10, diethanolamine cetyl phosphate, glyceryl stearate, PEG-100 stearate, and mixtures thereof
  • Suitable surfactants also include silicone surfactants. Suitable silicone surfactants include dimethicone based surfactants, surfactant silicone elastomers, and combinations thereof. In one embodiment, surfactant silicone elastomers or other silicone surfactants are uses herein. [0039] In one embodiment, the surfactant is a silicone copolyol. This material also allows a controlled rate of the delivery of the pharmaceutical agent to the substrate. That is, the dispersing agent functions as a drug release modulator to control the rate at which the pharmaceutical agent is released for delivery to the substrate.
  • the silicone copolyol are polydimethyl siloxanes that have been modified to include polyether side or pendant chains such as polyethylene oxide chains, polypropylene oxide chains, mixtures of these chains, and polyether chains containing moieties derived from both ethylene oxide and propylene oxide. Also included are polydimethyl siloxanes that have been modified to include polyglycerine side chains. Other examples include alkyl-modified dimethicone copolyols, (i.e., compounds that contain C2- C30 pendant side chains). Still other useful dimethicone copolyols include materials having various cationic, anionic, amphoteric, and zwitterionic pendant moieties.
  • dimethicone copolyols also include lauryl dimethicone copolyol, dimethicone copolyol acetate, dimethicone copolyol adipate, dimethicone copolyolamine, and dimethicone copolyol behenate. See International Cosmetic Ingredient Dictionary, Fifth Edition, 1993. [0042] Examples of commercially available dimethicone copolyols useful herein sold by Dow Coming Corporation are Dow Corning.RTM. 190, 193, Q2-5220, 2501 Wax, 2-5324 fluid, and 3225C (this later material being sold as a mixture with cyclomethicone).
  • Cetyl dimethicone copolyol is commercially available as a mixture with polyglyceryl-4 isostearate (and) hexyl laurate and is sold under the tradename ABIL.RTM. WE-09 (available from Goldschmidt). Cetyl dimethicone copolyol is also commercially available as a mixture with hexyl laurate (and) polyglyceryl-3 oleate (and) cetyl dimethicone and is sold under the tradename ABIL.RTM. WS-08 (also available from Goldschmidt). Other nonlimiting examples include the SILWET series and SILSOFT series available from Crompton/OSi.
  • the composition contains from about 0.1 to about 25 wt. % surfactant, alternatively from about 0.5% to about 10 wt. %. Mixtures of surfactants can also be used.
  • the pharmaceutical agent used herein is lipid soluble.
  • agents include drugs used in dermatology for the treatment of dermatoses (such as clobetasol, betamethasone dipropionate, hydrocortisone, dexamethasone sodium phosphate, retinal, tretinoin, isotretinoin, dapsone, calipotriene, ketoconazole, clotrimazole, itraconazole and arotinoid), drugs for hormonal replacement therapy (such as estradiol, ethinyl estradiol and norethindrone), drugs that inhibit the synthesis and actions of adrenocortical hormones (such as Cortisol, cortisone and prednisone), drugs such as clonidine, scopolamine, propranolol, estradiol, phenylpropanolamine hydrochloride, ouabain, atropine, haloperidol, isosorbide, nitroglycerin, ibuprofen, ubiquinones, indome
  • compositions of the invention contain from about 0.001 to about 10 wt. % lipid soluble pharmaceutical agent, alternatively from about 0.01% to about 5 wt. %.
  • various excipients may be incorporated into the composition. As generally understood by those skilled in the art, excipients are additives that are used to convert the pharmaceutical agent into appropriate dosage forms that are suitable for application to the substrate. Excipients may also be added to stabilize the composition and to optimize application characteristics, such as flowability.
  • excipients examples include, but are not limited to, those that are found in the CTFA ingredient Database and the handbook of pharmaceutical excipients such as absorbents, anticacking agents, antistatic agents, astringents, binders, buffering agents, bulking agents, chelating agents, colorants, cosmetic astringents, cosmetic biocides, deodorant agents, emollients, external analgesics, film formers, flavoring agents, fragrance ingredients, humectants, lytic agents, moisturizing agents, occlusivity enhancers, opacifying agents, oxidizing agents, reducing agents, penetration enhancers including oleic acid, azone, methyl laurate, lauryl alcohol and ethyl oleate, pesticides, plasticizers, preservatives, skin bleaching agents, skin conditioning agents, skin protectants, slip modifiers, solubilizing agents, solvents, sunscreen agents, surface modifiers, surfactants and emulsifying agents, suspending agents,
  • excipients include, but are not limited to, sugars and derivatives, starch derivatives, cellulosic materials, polysaccharides, polyethers, polyvinyl alcohols, acrylic and methacrylic acid polymers, pyrrolidone derivatives, glycuronam polymer and derivatives, solid diluents, solid lubricants, suspending agents, cyclodextrins, and others.
  • cosmetic, personal care, and cosmeceutical components may be included aside from the excipient or excipients.
  • suitable cosmetic, personal care, and cosmeceutical components include, but are not limited to, sunscreen agents, lipid soluble vitamins, alcohols, fatty alcohols and polyols, aldehydes, alkanolamines, alkoxylated alcohols, alkoxylated amides, alkoxylated amines, alkoxylated carboxylic acids, amides including salts, amines, amino acids including salts and alkyl substituted derivatives, esters, alkyl substituted and acyl derivatives, polyacrylic acids, acrylamide copolymers, adipic acid copolymers, alcohols, aminosilicones, biological polymers and derivatives, butylene copolymers, carbohydrates, carboxylic acids, carbomers, esters, ethers and polymeric ethers, glyceryl esters and derivatives, halogen
  • compositions of the invention can be made by merely mixing all the ingredients and subjecting resultant mixture to shear force to form the desired product.
  • Any type of mixing and shearing equipment may be used to perform these steps such as a batch mixer, planetary mixer, single or multiple screw extruder, dynamic or static mixer, colloid mill, homogenizer, sonolator, or a combination thereof.
  • the pharmaceutical agent is first mixed with the surfactant.
  • the resultant mixture is then added to the swollen silicone elastomer.
  • the method of delivering the pharmaceutical agent to the substrate further includes the step of applying the composition of the invention to the substrate to deliver the pharmaceutical agent to the substrate. Upon application, a film is formed on the substrate. The film contains the pharmaceutical agent. Following application, the pharmaceutical agent is delivered through the film to the substrate.
  • the composition is applied to the skin to deliver the pharmaceutical agent to the skin.
  • the composition may be applied, i.e., rubbed or coated, directly onto the skin.
  • the composition may be deposited on a transdermal patch prior to application to the substrate.
  • Clobetasol was dispersed in Dow Corning® Emulsifier 10 (a silicone alkylmethyl glycol).
  • Dow Corning® Elastomer 10 a silicone elastomer blended in decamethyl cyclopentasiloxane to form a gel
  • Dow Corning® 9041 a silicone elastomer in dodecamethyl pentasiloxane
  • Decamethyl cyclopentasiloxane was added to the mixture if necessary to make 100 wt %.
  • the clobetasol was mixed directly with the Elastomer 10.
  • Emulsifier 10 10%
  • Emulsifier 10 2.5%
  • Emulsifier 10 10%

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Abstract

L'invention concerne une composition pour administrer un agent pharmaceutique soluble lipidique à un substrat, cette composition comprenant un mélange sensiblement anhydre contenant un solvant, un élastomère de silicone, un tensioactif et un agent pharmaceutique soluble lipidique.
PCT/US2006/020300 2005-06-13 2006-05-24 Vehicule pour l'administration d'agents pharmaceutiques solubles lipidiques topiques Ceased WO2006138035A1 (fr)

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Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009007764A3 (fr) * 2007-07-10 2009-08-06 Egis Gyogyszergyar Nyilvanosan Préparations pharmaceutiques contenant des silicones hautement volatiles
WO2010089617A3 (fr) * 2009-02-06 2011-06-16 EGIS GYÓGYSZERGYÁR Nyilvánosan Müködö Részvénytársaság Préparations pharmaceutiques transdermiques
WO2012007776A3 (fr) * 2010-07-12 2012-06-07 Egis Gyógyszergyár Nyilvánosan Működő Részvénytársaság Formulation désinfectante et antiseptique à teneur réduite en iode
WO2014134502A1 (fr) * 2013-02-28 2014-09-04 Novan, Inc. Compositions topiques et leurs procédés d'utilisation
AP3434A (en) * 2010-07-19 2015-10-31 Egis Semisolid pharmaceutical formulations
US9289442B2 (en) 2011-07-05 2016-03-22 Novan, Inc. Topical compositions
US9427605B2 (en) 2005-03-24 2016-08-30 Novan, Inc. Cosmetic treatment with nitric oxide, device for performing said treatment and manufacturing method therefor
US9757397B2 (en) 2011-07-05 2017-09-12 Novan, Inc. Methods of manufacturing topical compositions and apparatus for the same
US10045935B2 (en) 2012-07-31 2018-08-14 Egis Pharmaceuticals Plc Transdermal formulation containing COX inhibitors
US10206947B2 (en) 2013-08-08 2019-02-19 Novan, Inc. Topical compositions and methods of using the same
US10226483B2 (en) 2013-08-08 2019-03-12 Novan, Inc. Topical compositions and methods of using the same
US10912743B2 (en) 2016-03-02 2021-02-09 Novan, Inc. Compositions for treating inflammation and methods of treating the same
US11154535B2 (en) 2012-07-31 2021-10-26 Egis Pharmaceuticals Plc Transdermal formulation containing COX inhibitors
US11166980B2 (en) 2016-04-13 2021-11-09 Novan, Inc. Compositions, systems, kits, and methods for treating an infection

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Cited By (29)

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US9427605B2 (en) 2005-03-24 2016-08-30 Novan, Inc. Cosmetic treatment with nitric oxide, device for performing said treatment and manufacturing method therefor
CN101815510B (zh) * 2007-07-10 2013-01-16 埃吉斯药物股份公开有限公司 包含高挥发性硅氧烷的药物制剂
AU2008273905B2 (en) * 2007-07-10 2014-02-20 Egis Gyogyszergyar Nyilvanosan Mukodo Reszvenytarsasag Pharmaceutical preparations containing highly volatile silicones
EA020094B1 (ru) * 2007-07-10 2014-08-29 Эгиш Дьёдьсердьяр Ньильваношан Мюкеде Ресвеньтаршашаг Фармацевтические препараты, содержащие легколетучие силиконы
WO2009007764A3 (fr) * 2007-07-10 2009-08-06 Egis Gyogyszergyar Nyilvanosan Préparations pharmaceutiques contenant des silicones hautement volatiles
US9775908B2 (en) 2007-07-10 2017-10-03 Egis Gyogyszergyar Nyilvanosan Mukodo Reszvenytarsasag Pharmaceutical preparations containing highly volatile silicones
EA023502B1 (ru) * 2009-02-06 2016-06-30 Эгиш Дьёдьсердьяр Ньильваношан Мюкеде Ресвеньтаршашаг Трансдермальная фармацевтическая композиция (варианты)
WO2010089617A3 (fr) * 2009-02-06 2011-06-16 EGIS GYÓGYSZERGYÁR Nyilvánosan Müködö Részvénytársaság Préparations pharmaceutiques transdermiques
CN103349643A (zh) * 2009-02-06 2013-10-16 埃吉斯药物股份公开有限公司 透皮药物制剂
WO2012007776A3 (fr) * 2010-07-12 2012-06-07 Egis Gyógyszergyár Nyilvánosan Működő Részvénytársaság Formulation désinfectante et antiseptique à teneur réduite en iode
AP3434A (en) * 2010-07-19 2015-10-31 Egis Semisolid pharmaceutical formulations
US10500220B2 (en) 2011-07-05 2019-12-10 Novan, Inc. Topical compositions
US9289442B2 (en) 2011-07-05 2016-03-22 Novan, Inc. Topical compositions
US9757397B2 (en) 2011-07-05 2017-09-12 Novan, Inc. Methods of manufacturing topical compositions and apparatus for the same
US10265334B2 (en) 2011-07-05 2019-04-23 Novan, Inc. Anhydrous compositions
US10045935B2 (en) 2012-07-31 2018-08-14 Egis Pharmaceuticals Plc Transdermal formulation containing COX inhibitors
US11154535B2 (en) 2012-07-31 2021-10-26 Egis Pharmaceuticals Plc Transdermal formulation containing COX inhibitors
US10258564B2 (en) 2013-02-28 2019-04-16 Novan, Inc. Topical compositions and methods of using the same
US9855211B2 (en) 2013-02-28 2018-01-02 Novan, Inc. Topical compositions and methods of using the same
CN105392472A (zh) * 2013-02-28 2016-03-09 诺万公司 局部组合物及其使用方法
WO2014134502A1 (fr) * 2013-02-28 2014-09-04 Novan, Inc. Compositions topiques et leurs procédés d'utilisation
CN105392472B (zh) * 2013-02-28 2021-08-10 诺万公司 局部组合物及其使用方法
US11285098B2 (en) 2013-02-28 2022-03-29 Novan, Inc. Topical compositions and methods of using the same
US10226483B2 (en) 2013-08-08 2019-03-12 Novan, Inc. Topical compositions and methods of using the same
US10828323B2 (en) 2013-08-08 2020-11-10 Novan, Inc. Topical compositions and methods of using the same
US10206947B2 (en) 2013-08-08 2019-02-19 Novan, Inc. Topical compositions and methods of using the same
US11813284B2 (en) 2013-08-08 2023-11-14 Novan, Inc. Topical compositions and methods of using the same
US10912743B2 (en) 2016-03-02 2021-02-09 Novan, Inc. Compositions for treating inflammation and methods of treating the same
US11166980B2 (en) 2016-04-13 2021-11-09 Novan, Inc. Compositions, systems, kits, and methods for treating an infection

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