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WO2019224035A1 - Compositions pharmaceutiques topiques comprenant un corticostéroïde - Google Patents

Compositions pharmaceutiques topiques comprenant un corticostéroïde Download PDF

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Publication number
WO2019224035A1
WO2019224035A1 PCT/EP2019/062217 EP2019062217W WO2019224035A1 WO 2019224035 A1 WO2019224035 A1 WO 2019224035A1 EP 2019062217 W EP2019062217 W EP 2019062217W WO 2019224035 A1 WO2019224035 A1 WO 2019224035A1
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WIPO (PCT)
Prior art keywords
weight
composition according
composition
isopropyl myristate
corticosteroid
Prior art date
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PCT/EP2019/062217
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English (en)
Inventor
Begoña Duarte Lopez
Pere Guiro Coll
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Almirall SA
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Almirall SA
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Publication of WO2019224035A1 publication Critical patent/WO2019224035A1/fr
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Classifications

    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams

Definitions

  • the present invention relates to topical pharmaceutical spray compositions comprising a corticosteroid, a volatile silicone and a solvent selected from isopropyl myristate, isopropyl palmitate and diisopropyl adipate. Said compositions are stable and non-greasy, and can be easily applied over the skin and the scalp. The invention further relates to a process for the preparation of said compositions and to methods of treatment by administering the
  • Topical corticosteroids demonstrate anti-inflammatory, anti-pruritic and
  • vasoconstrictive actions They are generally used to relieve the redness, skin edema (swelling), itching, crusting, flaking, blistering, cracking, oozing and discomfort of psoriasis, atopic dermatitis (atopic eczema) and other pathologies of the skin like contact dermatitis, seborrheic dermatitis, xerotic eczema, discoid eczema, venous eczema, dermatitis herpetiformis, neurodermatitis or autoeczematization.
  • topical corticosteroid products are available as creams, ointments, gels, foams, lotions and sprays.
  • semisolid dosage forms such as creams, ointments and gels are widely used.
  • a semisolid dosage form is applied on the skin, it is typically“rubbed in” which may further irritate the intended site of application.
  • These dosage forms may also cause clogging of pores and therefore block delivery of a suitable quantity of the active ingredient to the skin.
  • these types of semisolid compositions are difficult to apply and in some cases require the aid of a third person to apply them to areas that are difficult to access.
  • 5,972,920 describes topical sprayable formulations of clobetasol propionate characterized by a carrier compound formed of a combination of two components in a volume ratio of about 50/50, wherein the first carrier component is selected from the group consisting essentially of ethyl alcohol and isopropyl alcohol and the second carrier component is selected from the group consisting essentially of isopropyl myristate, isopropyl palmitate, octyl palmitate, octyl isononanoate and isocetyl stearate.
  • This patent covers the marketed formulation Clobex® spray, that comprises ethanol in an amount of about 50% w/w of the composition.
  • the high concentration of alcohol may cause burning at the site of application. This high concentration of alcohol also might cause dryness and itching at the application site.
  • Topical ethanol-free sprayable formulations of clobetasol propionate have been described in the International PCT Publications No. WO 2004/1 12798 and WO 2007/063254. These POT Publications disclose topical ethanol-free pharmaceutical compositions comprising clobetasol propionate, a volatile silicone and an oily phase such as sweet almond oil. However, the pharmaceutical compositions described result in greasy, and in some cases unstable formulations, unpleasant for the patient and not suitable for scalp application.
  • the International PCT Publication No. WO 2017/037663 describes topical pharmaceutical compositions comprising clobetasol propionate in submicron size droplets with oily excipients dispersed in an aqueous medium with a low alcohol content. Due to the high water
  • compositions do not dry quickly and might cause dripping at the application site, which makes them unpleasant for the patient and not suitable for hair-covered skin and hairy scalp.
  • topical pharmaceutical spray compositions comprising a) a corticosteroid, b) a volatile silicone and c) a solvent selected from isopropyl myristate, isopropyl palmitate and diisopropyl adipate are stable and exhibit comparable efficacy to other corticosteroid spray compositions available in the market.
  • Some commercially available formulations contain alcohol in order to have a fast drying action. This alcohol content may cause a burning and stinging sensation that is mitigated with the new composition.
  • Other topical spray compositions available in the market contain an aqueous vehicle which does not dry quickly and causes dripping at the application site.
  • the present invention due to their physicochemical properties, dry quickly, are easily applicable to the skin , including hairy areas, and are non-greasy, giving a more pleasant use to the patient.
  • compositions of the present invention do not cause burning, dryness and itching at the application site, and are stable, non-greasy and non-stinging.
  • the invention further relates to a composition as defined above for use in the treatment or prevention of psoriasis, atopic dermatitis (atopic eczema) and other skin disorders or diseases.
  • the invention further relates to the use of a composition as defined above for the manufacture of a medicament for the treatment or prevention of psoriasis, atopic dermatitis (atopic eczema) and other skin disorders or diseases.
  • the invention further relates to a method for treating a subject afflicted with psoriasis, atopic dermatitis (atopic eczema) and other skin disorders or diseases, which comprises applying to the affected area of skin of said subject an effective amount of a topical pharmaceutical composition as defined above.
  • component a) is a corticosteroid.
  • the corticosteroid is selected from alclometasone, amcinonide, betamethasone, clobetasol, desonide, desoximetasone, dexamethasone, diflorasone, fluocinolone, fluocinonide, flurandrenolide, fluticasone, halcinonide, halobetasol, hydrocortisone, mometasone, prednicarbate, triamcinolone and pharmaceutically acceptable salts, esters or acetonides thereof, and mixtures thereof.
  • the corticosteroid is selected from betamethasone dipropionate, clobetasol propionate, desoximetasone, halobetasol propionate, triamcinolone acetonide, and mixtures thereof.
  • the amount of a) corticosteroid is present in the range of 0.001 to 2.5% by weight.
  • the corticosteroid is present in the range of 0.005 to 0.5% by weight. More preferably the corticosteroid is present in the range of 0.01 to 0.5% by weight.
  • the topical pharmaceutical composition comprises 0.01 %, 0.025%, 0.05%, 0.1 %, 0.25% or 0.5% by weight of the corticosteroid.
  • the corticosteroid is betamethasone dipropionate.
  • Betamethasone dipropionate is chemically known as 9-fluoro-1 1 b, 17,21 -trihydroxy-16b- methylpregna-1 ,4-diene-3,20-dione 17,21 -dipropionate, and is represented by the structural Formula 1 , which has the empirical formula C28H37FO7, and a molecular weight of 504.60 g/mol.
  • betamethasone dipropionate may be replaced by other pharmacologically active derivatives of betamethasone such as pharmaceutically acceptable salts of betamethasone, betamethasone base form, other ester forms, its isomer forms, its enantiomers, and solvate derivatives thereof.
  • Betamethasone dipropionate might be amorphous, crystalline or mixtures thereof, and might exist in different crystalline forms or polymorphs.
  • the amount of a) betamethasone dipropionate is present in the range of 0.001 to 0.1 % by weight.
  • betamethasone dipropionate is present in the range of 0.0064 to 0.064% by weight. More preferably betamethasone dipropionate is present in an amount of 0.0064%, 0.0128%,
  • the topical pharmaceutical composition comprises 0.064% by weight of betamethasone dipropionate.
  • the corticosteroid is clobetasol or pharmaceutically acceptable salts or esters thereof.
  • the corticosteroid is clobetasol propionate.
  • Clobetasol propionate is chemically known as 21-chloro-9-fluoro-1 i p,17-dihydroxy-16p- methylpregna-1 ,4-diene-3,20-dione 17-propionate, and is represented by the structural Formula 2, which has the empirical formula C25H32CIFO5, and a molecular weight of 466.97 g/mol.
  • clobetasol propionate may be replaced by other pharmacologically active derivatives of clobetasol such as pharmaceutically acceptable salts of clobetasol, clobetasol base form, other ester forms, its isomer forms, its enantiomers, and solvate derivatives thereof.
  • Clobetasol propionate might be amorphous, crystalline or mixtures thereof, and might exist in different crystalline forms or polymorphs.
  • the amount of a) clobetasol propionate is present in the range of 0.001 to 0.1 % by weight.
  • clobetasol propionate is present in the range of 0.005 to 0.05% by weight.
  • More preferably clobetasol propionate is present in an amount of 0.005%, 0.01 %, 0.015%, 0.02%, 0.025%, 0.03%, 0.035%, 0.04%, 0.045% or 0.05% by weight based on the total weight of the composition.
  • the topical pharmaceutical composition comprises 0.05% by weight of clobetasol propionate.
  • the corticosteroid is desoximetasone or pharmaceutically acceptable salts or esters thereof.
  • the corticosteroid is desoximetasone.
  • Desoximetasone is chemically known as (1 i p,16a)-9-fluoro-1 1 ,21 -dihydroxy-16-methylpregna- 1 ,4-diene-3,20-dione, and is represented by the structural Formula 3, which has the empirical formula C22H29FO4, and a molecular weight of 376.47 g/mol.
  • desoximetasone may be replaced by other pharmacologically active derivatives of desoximetasone such as pharmaceutically acceptable salts of desoximetasone, its ester forms, its isomer forms, its enantiomers, and solvate derivatives thereof.
  • Desoximetasone might be amorphous, crystalline or mixtures thereof, and might exist in different crystalline forms or polymorphs.
  • the amount of a) desoximetasone is present in the range of 0.01 to 1 % by weight.
  • desoximetasone is present in the range of 0.05 to 0.25% by weight.
  • desoximetasone is present in an amount of 0.05%, 0.10%, 0.15%, 0.20% or 0.25% by weight based on the total weight of the composition.
  • the topical pharmaceutical composition comprises 0.25% by weight of desoximetasone.
  • the corticosteroid is halobetasol or pharmaceutically acceptable salts or esters thereof.
  • the corticosteroid is halobetasol propionate.
  • Halobetasol propionate is chemically known as (6a,1 i p,16P)-21-Chloro-6,9-difluoro-1 1-hydroxy- 16-methyl-17-(1-oxopropoxy)pregna-1 ,4-diene-3,20-dione, and is represented by the structural Formula 4, which has the empirical formula C25H31CIF2O5, and a molecular weight of 484.96 g/mol.
  • halobetasol propionate may be replaced by other pharmacologically active derivatives of halobetasol such as pharmaceutically acceptable salts of halobetasol, halobetasol base form, other ester forms, its isomer forms, its enantiomers, and solvate derivatives thereof.
  • Halobetasol propionate might be amorphous, crystalline or mixtures thereof, and might exist in different crystalline forms or polymorphs.
  • the amount of a) halobetasol propionate is present in the range of 0.001 to 0.1 % by weight.
  • halobetasol propionate is present in the range of 0.005 to 0.05% by weight.
  • More preferably halobetasol propionate is present in an amount of 0.005%, 0.01 %, 0.015%, 0.02%, 0.025%, 0.03%, 0.035%, 0.04%, 0.045% or 0.05% by weight based on the total weight of the
  • the topical pharmaceutical composition comprises 0.05% by weight of halobetasol propionate.
  • the corticosteroid is triamcinolone or pharmaceutically acceptable salts, esters or acetonides thereof.
  • the corticosteroid is triamcinolone acetonide.
  • Triamcinolone acetonide is chemically known as (1 i ,16a)-9-fluoro-1 1 ,21 -dihydroxy-16, 17-[(1- methylethylidene)bis(oxy)]pregna-1 ,4-diene-3,20-dione, and is represented by the structural Formula 5, which has the empirical formula C24H31FO6, and a molecular weight of 434.50 g/mol.
  • triamcinolone acetonide may be replaced by other pharmacologically active derivatives of triamcinolone such as pharmaceutically acceptable salts of triamcinolone, triamcinolone base form, its ester forms, its isomer forms, its enantiomers, and solvate derivatives thereof.
  • Triamcinolone acetonide might be amorphous, crystalline or mixtures thereof, and might exist in different crystalline forms or polymorphs.
  • the amount of a) triamcinolone acetonide is present in the range of 0.01 to 0.5% by weight.
  • triamcinolone acetonide is present in the range of 0.05 to 0.2% by weight. More preferably triamcinolone acetonide is present in an amount of 0.05%, 0.1 %, 0.15% or 0. 2% by weight based on the total weight of the composition.
  • the topical pharmaceutical composition comprises 0.2% by weight of triamcinolone acetonide.
  • the corticosteroid is the only one active ingredient in the composition.
  • the only one active ingredient in the composition is betamethasone dipropionate.
  • the only one active ingredient in the composition is clobetasol propionate.
  • the only one active ingredient in the composition is desoximetasone.
  • the only one active ingredient in the composition is halobetasol propionate.
  • component b) is a volatile silicone.
  • volatile silicone as used herein means a polyorganosiloxane compound which has a measurable pressure under ambient condition.
  • the volatile silicone may be linear or cyclic.
  • cyclic volatile silicones according to the invention are polydimethylcyclosiloxanes, which can be represented by the Formula 6:
  • the polydimethylcyclosiloxane is the octamethylcyclotetrasiloxane.
  • Octamethylcyclotetrasiloxane has a boiling point of 176°C, a viscosity of 2.3 centistokes at 25° C, and is represented by the formula [(Me 2 )SiO] 4 . It is also known as cyclomethicone 4 or D4.
  • cyclomethicone 4 or D4 When“n” represents 5, the polydimethylcyclosiloxane is the decamethylcyclopentasiloxane.
  • Decamethylcyclopentasiloxane has a boiling point of 210°C, a viscosity of 3.87 centistokes at 25° C, and is represented by the formula [(Me2)SiO]s. It is also known as cyclopentasiloxane, cyclomethicone 5 or D5.
  • the polydimethylcyclosiloxane is the dodecamethylcyclohexasiloxane.
  • Dodecamethylcyclohexasiloxane has a boiling point of 245°C, a viscosity of 6.62 centistokes at 25° C and is represented by the formula [(Me2)SiO]6. It is also known as cyclomethicone 6 or D6.
  • the cyclic volatile silicone according to the invention is selected from cyclomethicone 4, cyclomethicone 5, cyclomethicone 6 and mixtures thereof.
  • the cyclic volatile silicone is cyclomethicone 5.
  • the linear volatile silicones according to the invention are low molecular weight linear polysiloxanes such as hexamethyldisiloxane and octamethyltrisiloxane or low molecular weight dimethicones.
  • the linear volatile silicones generally have a viscosity of less than approximately 5 centistokes at 25° C., whereas the cyclic volatile silicones have a viscosity of less than approximately 10 centistokes at 25°C.
  • the linear volatile silicone according to the invention is selected from:
  • the linear volatile silicone is hexamethyldisiloxane.
  • the volatile silicone is selected from cyclomethicone 4, cyclomethicone 5,
  • cyclomethicone 6 hexamethyldisiloxane, octamethyltrisiloxane and mixtures thereof.
  • the volatile silicone is selected from cyclomethicone 5,
  • the volatile silicone is cyclomethicone 5.
  • the volatile silicone is hexamethyldisiloxane.
  • topical pharmaceutical composition according to the invention comprises from 1 to 98% by weight of the volatile silicone.
  • the topical pharmaceutical composition comprises from 10 to 85% by weight of the volatile silicone.
  • the topical pharmaceutical composition comprises from 20 to 75% by weight of the volatile silicone.
  • the topical pharmaceutical composition comprises from 30 to 65% by weight of the volatile silicone.
  • the topical pharmaceutical composition comprises from 38 to 60% by weight of the volatile silicone.
  • component c) is a solvent selected from isopropyl myristate, isopropyl palmitate and diisopropyl adipate.
  • Isopropyl myristate is the ester of isopropyl alcohol and myristic acid. It is chemically known as propan-2-yl tetradecanoate, and is represented by structural Formula 7.
  • Isopropyl palmitate is the ester of isopropyl alcohol and palmitic acid. It is chemically known as propan-2-yl hexadecanoate, and is represented by structural Formula 8.
  • Diisopropyl adipate is the diester of isopropyl alcohol and adipic acid. It is chemically known as bis(1-methylethyl)hexanedioate, and is represented by structural Formula 9.
  • the solvent may be selected from isopropyl myristate, isopropyl palmitate, octyl palmitate, octyl isonotate, isocetyl stearate, squalene, C12-C15 alkyl benzoate, coco- caprylate/caprate, diisopropyl adipate, dimethiconol, apricot kernel oil peg-6 ester, peg-15 stearyl ether, isopropyl stearate, isopropyl isostearate, glyceryl ricinoleate, diisopropyl dimer dilinoleate, cethyl palmitate, cetearyl isononanoate, dimethyl isosorbide and mixtures thereof.
  • component c) is a solvent selected from isopropyl myristate, isopropyl palmitate, diisopropyl adipate, dimethyl isosorbide, and mixtures thereof.
  • component c) is a solvent selected from isopropyl myristate, isopropyl palmitate and diisopropyl adipate.
  • the solvent is isopropyl myristate.
  • the solvent is isopropyl palmitate.
  • the solvent is diisopropyl adipate.
  • the topical pharmaceutical composition according to the invention comprises from 1 to 98% by weight of the solvent.
  • the topical pharmaceutical composition comprises from 10 to 85% by weight of the solvent. In a more preferred embodiment, the topical pharmaceutical composition comprises from 20 to 75% by weight of the solvent.
  • the topical pharmaceutical composition comprises from 30 to 65% by weight of the solvent.
  • the topical pharmaceutical composition comprises from 38 to 60% by weight of the solvent.
  • the present invention provides topical pharmaceutical compositions comprising
  • the topical pharmaceutical composition of the invention comprises
  • cyclomethicone 5 1 to 98% by weight of cyclomethicone 5, preferably 10 to 85% by weight, more preferably 20 to 75% by weight, and
  • topical pharmaceutical composition of the invention comprises
  • topical pharmaceutical composition of the invention comprises
  • topical pharmaceutical composition of the invention comprises
  • the present invention provides topical pharmaceutical compositions comprising
  • the topical pharmaceutical composition of the invention comprises
  • topical pharmaceutical composition of the invention comprises
  • topical pharmaceutical composition of the invention comprises
  • the topical pharmaceutical composition of the invention comprises a) 0.05% by weight of clobetasol propionate,
  • the topical pharmaceutical composition of the invention comprises less than 10% of water, preferably less than 5%, more preferably less than 2%.
  • the topical pharmaceutical composition of the invention is substantially free of water. More preferably, the topical pharmaceutical composition of the invention does not comprise water.
  • the topical pharmaceutical composition of the invention comprises less than 15% of an alcohol, preferably less than 10% and more preferably less than 5%.
  • the topical pharmaceutical composition of the invention comprises less than 2% of an alcohol.
  • the topical pharmaceutical composition of the invention is substantially free of ethanol or isopropanol.
  • the topical pharmaceutical composition of the invention does not comprise ethanol or isopropanol.
  • the topical pharmaceutical compositions according to the invention may optionally further comprise other well-known pharmaceutically and/or cosmetically acceptable additives, such as, e.g. anti-irritants, antioxidants, chelating agents, emollients, bulking agents, penetration enhancers, thickening agents or viscosity correctors, skin conditioning agents, humectants, preservatives, co-solvents, surfactants or emulsifiers, defoamers or antifoamings agents, propellants, colouring agents and the likes, or mixtures thereof.
  • additives such as, e.g. anti-irritants, antioxidants, chelating agents, emollients, bulking agents, penetration enhancers, thickening agents or viscosity correctors, skin conditioning agents, humectants, preservatives, co-solvents, surfactants or emulsifiers, defoamers or antifoamings agents, propellants, colouring agents
  • the topical pharmaceutical compositions according to the invention may optionally further comprise other well-known pharmaceutically and/or cosmetically acceptable additives, such as, e.g. anti-irritants, antioxidants, chelating agents, emollients, bulking agents, penetration enhancers, thickening agents or viscosity correctors, skin conditioning agents, humectants, preservatives, co-solvents, surfactants or emulsifiers, defoamers or antifoamings agents, colouring agents and the likes, or mixtures thereof.
  • other well-known pharmaceutically and/or cosmetically acceptable additives such as, e.g. anti-irritants, antioxidants, chelating agents, emollients, bulking agents, penetration enhancers, thickening agents or viscosity correctors, skin conditioning agents, humectants, preservatives, co-solvents, surfactants or emulsifiers, defoamers or antifoamings agents
  • Suitable anti-irritants are aloe vera, chamomile, alpha-bisabolol, cola nitida extract, green tea extract, tea tree oil, licoric extract, batyl alcohol (ooctadecyl glyceryl ether), selachyl alcohol (a-9-octadecenyl glyceryl ether), chimyl alcohol (a-hexadecyl glyceryl ether), panthenol, allantoin, caffeine or other xanthines, glycyrrhizic acid and derivatives thereof, and mixtures thereof.
  • the antioxidants used can be any antioxidant which is suitable or customary for cosmetic and/or dermatological applications.
  • Suitable antioxidants are advantageously selected from the group consisting of amino acids (for example glycine, histidine, tyrosine, tryptophan) and derivatives thereof, imidazoles (e.g. urocanic acid) and derivatives thereof, peptides such as D,L-carnosine, D-carnosine, L-carnosine and derivatives thereof (e.g. anserine), carotenoids, carotenes (e.g. a- carotene, b-carotene, lycopene) and derivatives thereof, lipoic acid and derivatives thereof (e.g.
  • thiols e.g. thioredoxin, glutathione, cysteine, cystine, cystamine and the glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, y-linoleyl, cholesteryl and glyceryl esters thereof
  • salts thereof dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and sulphoximine compounds (e.g.
  • buthionine sulphoximines in very small tolerated doses (e.g. pmol to pmol/kg), also (metal) chelating agents (e.g. a-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), a-hydroxy acids (e.g.
  • citric acid citric acid, lactic acid, malic acid
  • humic acid bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and derivatives thereof
  • unsaturated fatty acids and derivatives thereof e.g. g-linolenic acid, linoleic acid, oleic acid
  • folic acid and derivatives thereof ubiquinone and ubiquinol and derivatives thereof
  • vitamin C and derivatives e.g. ascorbyl palmitate, Mg ascorbyl phosphate, ascorbyl acetate
  • tocopherols and derivatives e.g.
  • vitamin E acetate vitamin E acetate
  • stilbene oxide, trans-stilbene oxide and the derivatives (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of said active ingredients which are suitable according to the invention, or mixtures thereof.
  • chelating agents are ethylenediaminetetraacetic acid (EDTA) and derivatives thereof (such as tetrasodium EDTA and disodium EDTA), sodium gluconate, sodium phytate, trisodium ethylenediamine disuccinate, derivatives thereof, and the like, or mixtures thereof.
  • Suitable emollients which can be used in the composition of the present invention include, for example, dodecane, squalane, cholesterol, isohexadecane, isononyl isononanoate, PPG ethers, petrolatum, lanolin, safflower oil, castor oil, coconut oil, cottonseed oil, palm kernel oil, palm oil, peanut oil, soybean oil, polyol carboxylic acid esters, derivatives thereof, and the like, or combinations thereof.
  • excipients that may act as bulking agents are starch, silicones, derivatives of celluloses such as carboxymethylcellulose, hydroxyethylcellulose and mixtures of thereof, polialcohols such as sorbitol and xylitol, derivatives thereof, and the like, or combinations thereof.
  • Suitable penetration enhancers can include, e.g., dimethylsulfoxide (DMSO), N- methyl pyrrolidine, dimethyl formamide (DMF), allantoin, urazole, N,N- dimethylacetamide (DMA), decylmethylsulfoxide, polyethylene glycol monolaurate, propylene glycol, propylene glycol monolaurate, glycerol monolaurate, lecithin, the 1 -substituted azacycloheptan-2-ones, particularly 1-n-dodecylcyclazacycloheptan-2-one, alcohols, glycerin, hyaluronic acid, transcutol, and the like, or combinations thereof.
  • Certain oil components e.g., certain vegetable oils such as, e.g., safflower oil, cottonseed oil and corn oil also can exhibit penetration enhancing properties.
  • Thickening agents or viscosity correctors can be included to generally thicken the liquid pharmaceutical compositions. While any suitable thickening agent can be included in the compositions of the present invention, a preferred thickening agent, when used, includes natural gums like carrageenan (E407, a polysaccharide obtained from red seaweeds), locust bean gum (E410, a natural gum polysaccharide from the seeds of the carob tree), pectin (E440, a polysaccharide obtained from apple or citrus-fruit), gelatine (E441 , made by partial hydrolysis of animal collagen), guar gum, agar-agar, starch tragacanth and xanthan gum or pectins and mixtures of thereof.
  • carrageenan E407, a polysaccharide obtained from red seaweeds
  • locust bean gum E410, a natural gum polysaccharide from the seeds of the carob tree
  • pectin E440, a polysaccharide
  • alginic acid bentonite and alginic acid derivatives such as sodium alginate (E401 ), potassium alginate (E402), ammonium alginate (E403), calcium alginate (E404) - polysaccharides from brown algae, and any combination thereof.
  • alginic acid derivatives such as sodium alginate (E401 ), potassium alginate (E402), ammonium alginate (E403), calcium alginate (E404) - polysaccharides from brown algae, and any combination thereof.
  • acrylic polymers like carbomers and cellulose derivatives like, carboxymethylcellulose calcium or sodium, methyl cellulose ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose,
  • hydroxypropylmethylcellulose methylcellulose or maltodextrin
  • polyvinyl alcohol povidone
  • propylene carbonate propylene glycol alginate, sodium alginate, sodium starch glycolate, or any combination thereof.
  • Suitable skin conditioning agents are hydrolyzed collagen, nicotinamide, Panthenol, sodium hyaluronate, vegetable extracts such as Dunaliella salina extract, Bobgunnia
  • Madagascariensis wood extract Tilia Cordata flower extract, sesame seed extract or Vitis Vinifera (grape)
  • cholesterol derivatives such as cholesteryl isostearate, cholesteryl chloride or cholesteryl nonanoate, tocopherol and peptides, or mixtures thereof.
  • humectants chemical substances that increase the spreading and penetrating properties of a liquid by lowering its surface tension
  • humectants include one or more cationic surfactants, such as benzalkonium chloride; non-ionic surfactants such as polyoxyethylene and
  • polyoxypropylene block copolymers polyoxyethylene fatty acid glycerides and oils (such as polyoxyethylene (6) caprylic/capric mono- and diglycerides), polyoxyethylene (40) hydrogenated castor oil; polyoxyethylene sorbitan esters, such as polysorbate 20 and polysorbate 80;
  • propylene glycol fatty acid esters such as propylene glycol laureate
  • glyceryl fatty acid esters such as glyceryl monostearate
  • sorbitan esters such as sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate and sorbitan monostearate
  • glyceryl fatty acid esters for example glyceryl monostearate
  • anionic surfactants such as sodium lauryl sulphate, sodium lauryl ether sulphate
  • fatty acids and salts thereof such as oleic acid, sodium oleate and triethanolamine oleate and mixtures thereof.
  • preservatives to prevent microbial contamination examples include alkylparabens (particularly methylparaben, ethylparaben, propylparaben and butylparaben), sodium benzoate, butylated hydroxy toluene, butylated hydroxyanisole, ethylenediamine tetraacetic acid, chlorobutanol, benzyl alcohol, phenylethylalcohol, phenoxyethanol, dehydroacetic acid, sorbic acid, undecylenic acid, potassium sorbate, benzalkonium chloride, benzethonium chloride, and mixtures thereof.
  • the amount of preservative generally utilized will vary depending upon the preservative selected.
  • co-solvents are, for example, nonionic surfactants from at least one of the following groups: products of the addition of 1 to 30 moles of ethylene oxide and/or 0 to 5 moles of propylene oxide onto linear C8-C22 fatty alcohols, C12-C22 fatty acids and alkyl phenols containing 8 to 15 carbons in the alkyl group; alkyl and/or alkenyl oligoglycosides containing 8 to 22 carbons in the alkyl group and ethoxylated analogs thereof; addition products of 1 to 15 moles of ethylene oxide with castor oil and/or hydrogenated castor oil; addition products of 15 to 60 moles of ethylene oxide with castor oil and/or hydrogenated castor oil; partial esters of glycerol and/or sorbitan with unsaturated or saturated, linear or branched fatty acids containing 12 to 22 carbons and/or hydroxycarboxylic acids containing 3 to 18 carbon atoms and addition products thereof with 1 to 30 moles
  • Particularly preferred solubilizing agents are products of the addition of 1 to 30 moles of ethylene oxide and/or 0 to 5 moles of propylene oxide onto linear C8-C22 fatty alcohols such as lauryl, myristyl, cetyl (palmityl), stearyl, oleyl, and ricinoleyl alcohols, or technical grade mixtures thereof such as cetostearyl alcohol or palmitoleyl alcohol.
  • linear C8-C22 fatty alcohols such as lauryl, myristyl, cetyl (palmityl), stearyl, oleyl, and ricinoleyl alcohols, or technical grade mixtures thereof such as cetostearyl alcohol or palmitoleyl alcohol.
  • surfactants or emulsifiers are the anionic surfactants such as sodium lauryl sulfate (sodium dodecyl sulfate, SLS, or SDS), and the related alkyl-ether sulfates such as sodium laureth sulfate (sodium lauryl ether sulfate or SLES), and sodium myreth sulfate.
  • anionic surfactants such as sodium lauryl sulfate (sodium dodecyl sulfate, SLS, or SDS)
  • alkyl-ether sulfates such as sodium laureth sulfate (sodium lauryl ether sulfate or SLES)
  • Others include, docusate (dioctyl sodium sulfosuccinate), perfluorooctanesulfonate (PFOS),
  • carboxylates that are the most common surfactants, comprise alkyl carboxylates , such as sodium stearate. More specialized species include sodium lauroyl sarcosinate and carboxylate- based fluorosurfactants such as perfluorononanoate and perfluorooctanoate (PFOA or PFO).
  • PFOA or PFO perfluorononanoate
  • PFO perfluorooctanoate
  • Polyethylene glycol derivatives of the castor oil or the hydrogenated castor oil such as PEG-30 castor oil, PEG-33 castor oil, PEG-35 castor oil, PEG-36 castor oil and PEG-40 castor oil, PEG- 30 hydrogenated castor oil and PEG-40 hydrogenated castor oil, PEG-80 glyceryl cocoate, derivatives thereof, and the like, or mixtures of thereof may also act as surfactants.
  • a defoamer or an anti-foaming agent is a chemical additive that reduces and hinders the formation of foam in the manufacturing process of liquids.
  • examples of this are oil based defoamers, powder defoamers based on silica, water based defoamers, silicone based defoamers, EO/PO based defoamers that contain polyethylene glycol and polypropylene glycol copolymers, and mixtures thereof.
  • propellant refers to the substance that helps in the propelling the composition out of the container.
  • Suitable examples of propellants are selected from the group consisting of conventional, non-ozone depleting hydrocarbon propellants, such as propane, butane, isobutene, cyclopropane, 1 ,1 ,1 ,2-tetrafluorethane, 1 ,1 ,1 ,2,3,3,3-heptafluoropropane, 1 ,1- difluoroethane, 1 ,1 ,1 ,3,3,3-hexafluoropropane, and mixtures thereof; fluorocarbon gas; and liquefied petroleum gas.
  • colouring agents are aluminum lake pigments produced from the FD&C dyes that are oil dispersible (but generally not oil soluble) and thus can be mixed with oils and fats, natural food dyes such as caramel, made from caramelized sugar, annatto, a reddish-orange dye made from the seed of the achiote, a green dye made from chlorella algae (chlorophyll), cochineal, a red dye derived from the cochineal insect, Dactylopius coccus, Betanin extracted from beets Turmeric (curcuminoids), Saffron (carotenoids), Paprika Elderberry juice, Pandan (Pandanus amaryllifolius), a green food colouring and Butterfly pea (Clitoria ternatea), a blue food dye and artificial colours dyes like FD&C Blue No. 1 - Brilliant Blue FCF, E133 (blue shade), FD&C blue No. 2 - Indigotine, E132 (dark blue shade), FD
  • the topical pharmaceutical composition of the invention is a solution to be sprayed.
  • the topical composition of the present invention is administered in the form of a sprayable composition.
  • the compositions according to the invention will preferably have a viscosity of less than 50 centistokes, and more preferably less than 10 centistokes.
  • the sprayable form, or spray can be obtained from the liquid solution using a conventional spraying system without pressurization.
  • the composition may be sprayed by means of a mechanical spraying device which pumps the composition from a container, bottle or equivalent.
  • the composition passes through a nozzle which can be aimed directly at the desired site of application.
  • the spraying mechanism must be capable of always delivering the same amount of active agent.
  • the mechanisms for controlling the amount of composition to be delivered by the spray are also known to those skilled in the art.
  • composition may be propelled by means of a gas, as is well known by the person skilled in the art.
  • propellants such as air or hydrocarbons are effective provided that they do not interfere with the composition.
  • the topical pharmaceutical spray composition of the present invention does not comprise propellants.
  • the invention further relates to a topical pharmaceutical spray composition as defined above for use in the treatment or prevention of psoriasis, atopic dermatitis (atopic eczema) and other skin disorders or diseases, such as contact dermatitis, seborrheic dermatitis, xerotic eczema, dyshidrosis, discoid eczema, venous eczema, dermatitis herpetiformis, neurodermatitis or autoeczematization.
  • atopic dermatitis atopic dermatitis
  • other skin disorders or diseases such as contact dermatitis, seborrheic dermatitis, xerotic eczema, dyshidrosis, discoid eczema, venous eczema, dermatitis herpetiformis, neurodermatitis or autoeczematization.
  • the invention relates to a topical pharmaceutical spray composition for use in the treatment or prevention of psoriasis.
  • plaque psoriasis as used herein includes plaque psoriasis (or psoriasis vulgaris), guttate psoriasis, inverse psoriasis, pustular psoriasis and erythrodermic psoriasis.
  • plaque psoriasis or psoriasis vulgaris
  • guttate psoriasis inverse psoriasis
  • pustular psoriasis erythrodermic psoriasis.
  • plaque psoriasis Preferably, plaque psoriasis.
  • the invention further relates to the use of a topical pharmaceutical spray composition as defined above for the manufacture of a medicament for the treatment or prevention of psoriasis, atopic dermatitis (atopic eczema) and other skin disorders or diseases, such as contact dermatitis, seborrheic dermatitis, xerotic eczema, dyshidrosis, discoid eczema, venous eczema, dermatitis herpetiformis, neurodermatitis or autoeczematization.
  • atopic dermatitis atopic dermatitis
  • other skin disorders or diseases such as contact dermatitis, seborrheic dermatitis, xerotic eczema, dyshidrosis, discoid eczema, venous eczema, dermatitis herpetiformis, neurodermatitis or autoeczematization.
  • the invention relates to the use of a topical pharmaceutical spray composition as defined above for the manufacture of a medicament for the treatment or prevention of psoriasis.
  • the invention further relates to a method for treating a subject afflicted with psoriasis, atopic dermatitis (atopic eczema) and other skin disorders or diseases, such as contact dermatitis, seborrheic dermatitis, xerotic eczema, dyshidrosis, discoid eczema, venous eczema, dermatitis herpetiformis, neurodermatitis or autoeczematization, which comprises applying to the affected area of skin of said subject an effective amount of a topical pharmaceutical composition as defined above.
  • atopic dermatitis atopic dermatitis
  • other skin disorders or diseases such as contact dermatitis, seborrheic dermatitis, xerotic eczema, dyshidrosis, discoid eczema, venous eczema, dermatitis herpetiformis, neurodermatitis or autoeczematization
  • the invention relates to a method for treating a subject afflicted with psoriasis.
  • BP betamethasone dipropionate
  • CP clobetasol propionate
  • CMT-5 cyclometicone 5
  • HMD hexamethyldisiloxane
  • IPM is isopropyl myristate
  • IPP is isopropyl palmitate
  • DIPA is diisopropyl adipate
  • DMI is dimethylisosorbide
  • UEA is undecylenic acid
  • PHE is phenoxyethanol
  • MePB/EtPB/PrPB is methylparaben/ethylparaben/propylparaben.
  • betamethasone propionate corresponds to 0.05%wt of betamethasone base.
  • Betamethasone dipropionate was dissolved in to corresponding solvent.
  • step 3 The volatile silicone was added to the solution of step 2, and the mixture was stirred to complete homogenization.
  • Clobetasol propionate was dissolved in to corresponding solvent. When corresponding, the preservative was added to the solution and the mixture was stirred to complete solubilization. 2) The volatile silicone was added to the solution of step 1 , and the mixture was stirred to complete homogenization.
  • Desoximetasone was dissolved in to corresponding solvent. When corresponding, the preservative was added to the solution and the mixture was stirred to complete solubilization.
  • step 2 2) The volatile silicone was added to the solution of step 1 , and the mixture was stirred to complete homogenization.
  • 2 lsobutane is used as a propellant, which can be interchanged by other propellants such as propane, butane, cyclopropane, 1 ,1 ,1 ,3,3,3,-hexafluoropropane, fluorocarbon gas and liquefied petroleum gas, or mixtures thereof.
  • Halobetasol propionate was dissolved in to corresponding solvent.
  • step 2 2) The volatile silicone was added to the solution of step 1 , and the mixture was stirred to complete homogenization.
  • 2 lsobutane is used as a propellant, which can be interchanged by other propellants such as propane, butane, cyclopropane, 1 ,1 ,1 ,3,3,3, -hexafluoropropane, fluorocarbon gas and liquefied petroleum gas, or mixtures thereof.
  • Triamcinolone acetonide was dissolved in to corresponding solvent.
  • step 2 2) The volatile silicone was added to the solution of step 1 , and the mixture was stirred to complete homogenization.
  • clobetasol spray formulations of the present invention were compared with Clobex® spray in a TPA model of ear inflammation in BALB/c mice.
  • the results show that clobetasol spray formulations of the present invention applied topically full inhibit the ear swelling induced by the topical application of TPA. This results are in concordance with those obtained with Clobex® spray.

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  • Life Sciences & Earth Sciences (AREA)
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  • Pharmacology & Pharmacy (AREA)
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Abstract

L'invention concerne des compositions de pulvérisation pharmaceutiques topiques comprenant un corticostéroïde, une silicone volatile et un solvant choisi parmi le myristate d'isopropyle, le palmitate d'isopropyle et l'adipate de diisopropyle. Lesdites compositions sont stables et non grasses, et peuvent être facilement appliquées sur la peau et le cuir chevelu. L'invention concerne en outre un procédé de préparation desdites compositions et des procédés de traitement par administration des compositions.
PCT/EP2019/062217 2018-05-24 2019-05-13 Compositions pharmaceutiques topiques comprenant un corticostéroïde Ceased WO2019224035A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210308231A1 (en) * 2018-12-21 2021-10-07 Gelita Ag Collagen hydrolysate for use with skin disorders and intestinal disorders
US12447161B2 (en) * 2021-06-25 2025-10-21 Rades Gmbh Topical pharmaceutical formulation

Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5972920A (en) 1998-02-12 1999-10-26 Dermalogix Partners, Inc. Formulation containing a carrier, active ingredient, and surfactant for treating skin disorders
US5990100A (en) 1998-03-24 1999-11-23 Panda Pharmaceuticals, L.L.C. Composition and method for treatment of psoriasis
WO2004112798A1 (fr) 2003-06-23 2004-12-29 Galderma Research & Development, S.N.C. Compositions sous forme de spray comprenant un actif pharmaceutique, au moins un silicone volatile et une phase huileuse non volatile
WO2007063254A1 (fr) 2005-11-30 2007-06-07 Galderma S.A. Composition sous forme de spray comprenant un corticoide et une phase huileuse
US20090104125A1 (en) * 2005-05-27 2009-04-23 Taro Pharmaceuticals North America, Inc. Stable liquid desoximethasone compositions with reduced oxidized impurity
US20100055137A1 (en) * 2004-08-31 2010-03-04 Stiefel Research Australia Pty Ltd Microemulsion & sub-micron emulsion process & compositions
US8272780B1 (en) 2009-08-21 2012-09-25 Rantec Power Systems, Inc. Multiple-unit thermal test apparatus for electrical devices
WO2015044857A1 (fr) 2013-09-25 2015-04-02 Ranbaxy Laboratories Limited Composition de pulvérisation topique d'halobétasol
WO2015072909A1 (fr) * 2013-11-14 2015-05-21 Lipidor Ab Véhicule topique pulvérisable et composition comprenant de la phosphatidylcholine
US9364485B2 (en) 2009-08-31 2016-06-14 Dr. Reddy's Laboratories Ltd. Topical formulations comprising a steroid
WO2016157112A1 (fr) * 2015-03-31 2016-10-06 Dr. Reddy’S Laboratories Limited Compositions de pulvérisation topiques de furoate de mométasone
WO2017037663A1 (fr) 2015-09-02 2017-03-09 Cadila Healthcare Limited Compositions topiques comprenant des corticostéroïdes

Patent Citations (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5972920A (en) 1998-02-12 1999-10-26 Dermalogix Partners, Inc. Formulation containing a carrier, active ingredient, and surfactant for treating skin disorders
US5990100A (en) 1998-03-24 1999-11-23 Panda Pharmaceuticals, L.L.C. Composition and method for treatment of psoriasis
WO2004112798A1 (fr) 2003-06-23 2004-12-29 Galderma Research & Development, S.N.C. Compositions sous forme de spray comprenant un actif pharmaceutique, au moins un silicone volatile et une phase huileuse non volatile
US20100055137A1 (en) * 2004-08-31 2010-03-04 Stiefel Research Australia Pty Ltd Microemulsion & sub-micron emulsion process & compositions
US20090104125A1 (en) * 2005-05-27 2009-04-23 Taro Pharmaceuticals North America, Inc. Stable liquid desoximethasone compositions with reduced oxidized impurity
US8715624B2 (en) 2005-05-27 2014-05-06 Taro Pharmaceuticals North America, Inc. Stable liquid desoximethasone compositions with reduced oxidized impurity
WO2007063254A1 (fr) 2005-11-30 2007-06-07 Galderma S.A. Composition sous forme de spray comprenant un corticoide et une phase huileuse
US8272780B1 (en) 2009-08-21 2012-09-25 Rantec Power Systems, Inc. Multiple-unit thermal test apparatus for electrical devices
US9439911B2 (en) 2009-08-31 2016-09-13 Dr. Reddy's Laboratories Ltd. Topical formulations comprising a steroid
US9364485B2 (en) 2009-08-31 2016-06-14 Dr. Reddy's Laboratories Ltd. Topical formulations comprising a steroid
US9433630B1 (en) 2009-08-31 2016-09-06 Dr. Reddy's Laboratories Ltd. Topical formulations comprising a steroid
US9655907B2 (en) 2009-08-31 2017-05-23 Dr. Reddy's Laboratories Ltd. Topical formulations comprising a steroid
US9877974B2 (en) 2009-08-31 2018-01-30 Dr. Reddy's Laboratories, Ltd. Topical formulations comprising a steroid
WO2015044857A1 (fr) 2013-09-25 2015-04-02 Ranbaxy Laboratories Limited Composition de pulvérisation topique d'halobétasol
WO2015072909A1 (fr) * 2013-11-14 2015-05-21 Lipidor Ab Véhicule topique pulvérisable et composition comprenant de la phosphatidylcholine
WO2016157112A1 (fr) * 2015-03-31 2016-10-06 Dr. Reddy’S Laboratories Limited Compositions de pulvérisation topiques de furoate de mométasone
WO2017037663A1 (fr) 2015-09-02 2017-03-09 Cadila Healthcare Limited Compositions topiques comprenant des corticostéroïdes

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210308231A1 (en) * 2018-12-21 2021-10-07 Gelita Ag Collagen hydrolysate for use with skin disorders and intestinal disorders
US12138297B2 (en) * 2018-12-21 2024-11-12 Gelita Ag Collagen hydrolysate for use with skin disorders and intestinal disorders
US12447161B2 (en) * 2021-06-25 2025-10-21 Rades Gmbh Topical pharmaceutical formulation

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