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
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• • 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
  • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
  • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
• • 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
  • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
  • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
  • A61K47/38—Cellulose; Derivatives thereof
• • 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

Definitions

• the invention relates to a corticosteroid-containing pharmaceutical preparation intended for topical use.
• Corticosteroids constitute a large group of compounds with a pregnene or pregnadiene backbone and with versatile medical uses. In particular they are used topically as anti-inflammatory dermatological medicines.
• Examples of corticosteroids on the market include hydrocortisone, dexamethasone, betamethasone, methylprednisolone, prednisolone, prednisone, beclomethasone, fludrocortisone, triamsinolone, desonide, fluprednidene, clobetasone, alclomethasone, momethasone, desoxymethasone, fluosinonide, budesonide and fluosinolone .
• ester-form glucocorticoids such as betamethasonide propionate
• Carbomer i.e. carboxyvinyl polymer
• Hydrocortisone gels are not available on the market. Attempts to prepare a hydrocortisone gel by using conventional gellants such as Carbomer polymer have failed owing to the poor stability of hydrocortisone.
• a corticosteroid-containing pharmaceutical formulation according to the invention is characterized in that the formulation has been brought to gel form by means of a gellant, the gellant being hydroxyalkyl cellulose.
• the corticosteroid may be any pharmaceutically acceptable corticosteroid.
• the corticosteroid is hydrocortisone.
• the hydroxyalkyl cellulose used as the gellant is hydroxyethyl cellulose or hydroxypropyl cellulose, in particular hydroxyethyl cellulose.
• the solvent used is preferably a mixture of water and a lower alcohol, such as ethanol or propanol.
• a mixture of water and ethanol or of water and isopropanol is especially preferable .
• Glycerol or propylene glycol is preferably added to the formulation in order to prevent skin drying caused by the alcohol (ethanol).
• alcohol ethanol
• some oil component such as Cetiol SN (cetearyl- isononanoate)
• suitable perfumes and preservatives include methylparahydroxybenzoate, propyl- parahydroxybenzoate and benzyl alcohol.
• hydrocortisone-containing gel batches I, II, III and IV were prepared. Batches I and II were prepared on a laboratory scale (1000 g/batch) and batches III and IV were prepared on an industrial scale (150 kg/batch). The soft gels were packed into polyethylene tubes. The stability of the gels was monitored for 18 months (batch I), 12 months (batch II) and 3 months (batches III and IV).
• the gels were prepared as follows: HEC was added to a mixture of water and ethanol (containing only a portion of the ethanol) while stirring, and the mixture was allowed to gel. Thereafter the glycerol was added while stirring. The balance of the ethanol was added while stirring. Thereafter the active ingredient was added to the gel while stirring.
• the batches were stored at a relative humidity of 60 %.
• the temperature was 25 °C (batches I, III and IV) and respectively 20 °C (batch II).
• the amount of degradation products may be at maximum 5 %, the amount of hydrocortisone should be 9.0 - 11.0 mg/g, and the pH should be 5 - 8.5.
• hydrocortisone gel formulations A, B, C and D were prepared, in which the gellant used was carboxyvinyl polymer Carbomer 980 or Carbomer 940, or polymer Stabileze R QM, which is a copolymer of methylvinyl ether and maleic acid anhydride, cross- bridged with 1 , 9-decadiene .
• These gellants yield a very low pH value (the pH of a 1 % aqueous dispersion of Carbomer polymer is 2.5 - 3.0), and therefore sodium hydroxide was added to adjust the pH to the desired range.
• the auxiliary compositions and hydrocortisone concentrations of the preparations are shown in Table 1, which also shows the stabilities of the preparations .
• Table 1 shows that, already after three months of storage, a large quantity of degradation products of hydrocortisone had formed. After six months of storage the concentration of hydrocortisone degradation products in preparations A, B and D clearly exceeded the guideline values (guideline value at maximum 5 % ) , and the concentration of degradation products in preparation C was also very high (4 %).

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Public Health (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• General Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Animal Behavior & Ethology (AREA)
• Inorganic Chemistry (AREA)
• General Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Engineering & Computer Science (AREA)
• Oil, Petroleum & Natural Gas (AREA)
• Dermatology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (3)

Publications (1)

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Family Applications (1)

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• 1997
  • 1997-12-23 FI FI974610A patent/FI974610A0/fi not_active Application Discontinuation
• 1998
  • 1998-12-21 EP EP98962440A patent/EP1047430A1/de not_active Withdrawn
  • 1998-12-21 WO PCT/FI1998/001000 patent/WO1999033471A1/en not_active Application Discontinuation
  • 1998-12-21 AU AU17607/99A patent/AU1760799A/en not_active Abandoned
• 2002
  • 2002-11-01 DK DK200200342U patent/DK200200342U3/da not_active IP Right Cessation

Non-Patent Citations (1)

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