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
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
  • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• • 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
  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
  • A61K9/4841—Filling excipients; Inactive ingredients
  • A61K9/4866—Organic macromolecular compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

• the present invention relates generally to softgels or soft gelatin capsules and fill
• compositions therefor and in particular to a soft gelatin capsule that contains a highly hydrophilic material.
• ibuprofen-containing soft gelatin capsules in which up to 30 parts by weight of ibuprofen
• polyoxypropylene polymer or in a mixture of from 30 to 76 parts by weight of a
• polyalkylene glycol and from 7 to 40 parts by weight of a surfactant having a very rapid
• Preferred suitable surfactants include,
• polyoxyethyleneglycerol trihydroxystearate polyoxyethylene (C 12 - 18 )-fatty
• alcohol ethers polyoxyethylene stearate, polyoxyethylenesorbitan mono(C 12 - 18 )-fatty
• ibuprofen may also be suspended in the fill.
• fill formulations may be liquid, semi-solid or solid, and are formed by
• ibuprofen 1-20% by weight water, and 4-12% by weight glycerine or propylene glycol in
• the preferred average molecular weight of the polyvinylpyrrolidone is 10,000-
• polyvinylpyrrolidone are used to prepare semi-solid and solid formulations for
• suppositiories two piece capsules, and tablets.
• the hydroxyl ions source e.g., sodium
• hydroxide or potassium hydroxide partially forms an ibuprofen salt, and the water forms
• concentrations i.e., greater than 30% by weight, of ibuprofen in solution in its free acid
• the present invention relates to a liquid softgel fill formulation comprising greater
• ibuprofen in free acid form in solution from about 30 to about 60%
• polyethylene glycol by weight polyethylene glycol; and from about 10 to about 30 % by weight of
• liquid softgel fill formulations containing ibuprofen in free acid More specifically, liquid softgel fill formulations containing ibuprofen in free acid
• softgel capsules comprised of a gelatin sheath enclosing such fill formulations
• glycol and at least 10% by weight of a polyvinylpyrrolidone having an average molecular
• the formulations may also include a
• the present invention relates to softgel fill formulations containing high
• concentrations i.e., greater than 30% by weight of ibuprofen in its free acid form
• solvent components being present in a defined amount in the composition, and with each
• the formulation also includes a
• formulations of the present invention are comprised of greater
• ibuprofen less than 30% and up to 40% or more by weight ibuprofen, from 30 to 60 % by weight
• polyethylene glycol and from 10 to 30 % by weight of polyvinylpyrrolidone.
• polyvinylpyrrolidone Preferably,
• the formulations are comprised of from 35 to 40% by weight ibuprofen, from 30 to 50 %
• polyethylene glycol by weight polyethylene glycol, and from 15 to 30% by weight of polyvinylpyrrolidone.
• a nasal decongestant such as pseudoephedrine
• hydrochloride or up to 10% of an antihistaminic, such as diphenhydramine
• hydrochloride may be included in the formulation.
• the preferred embodiments of the invention also contain at least about 10%,
• the composition preferably from about 1% to about 10% by weight of a surfactant.
• the surfactant preferably from about 1% to about 10% by weight of a surfactant.
• ibuprofen while being miscible with polyethylene glycol to form a clear solution.
• Suitable surfactants include esters of d-alpha tocopheryl, polyoxyethylene castor oil
• Polyoxyethylene castor oil derivatives are the
• reaction products of ethylene oxide and castor oil or hydrogenated castor oil sold, for example, as Cremophors by BASF.
• Suitable polyglycolyzed glycerides are sold under
• Vitamin E TPGS Company under the trademark Vitamin E TPGS.
• the polyethylene glycol component of the formulation should have an average
• the polyethylene glycol has an average molecular weight of at least about
• PEG 600 is especially preferred.
• the average molecular weight of the polyvinylpyrrolidone used in the present invention is the average molecular weight of the polyvinylpyrrolidone used in the present invention.
• formulations may be in the range of from 2,000 to 54,000, but preferably is in the range
• polyvinylpyrrolidones are sold under the
• polyvinylpyrrolidones have approximate molecular weights of 2,500 and 10,000
• the fill formulations may be prepared by heating the polyethylene glycol and
• the fill formulation is encapsulated into one-piece gelatin sheath or shell that
• a plasticizer to control the softness and flexibility of the sheath, water, and
• the softgel optionally, other additives, such as flavorants, colorants, opacifiers, etc.
• additives such as flavorants, colorants, opacifiers, etc.
• capsules may be produced in a known manner with a rotary die process in which a molten
• rollers and brought together at a convergent angle into the nip of a pair of roller dies that
• a fill formulation to be encapsulated is fed into the wedge-
• the gelatin ribbons are continuously conveyed between the dies, with portions of
• suitable sheath formulations may be selected from any suitable sheath formulations of the present invention.
• suitable sheath formulations may be selected from any suitable sheath formulations.
• gelatin examples include from about 35 to about 50 % by weight gelatin; at least 20% by weight, and
• a plasticizer preferably up to about 40 % by weight, of a plasticizer; and from about 25 to about 50 %
• capsule sheaths comprised of from about 45 to about 75 % by weight gelatin; from about
• plasticizer 20% to about 40 % by weight plasticizer; and from about 5 to about 15 % by weight
• the gelatin will normally have a bloom in the range of from about 150 to about
• 275 may be Type A or B gelatins or a mixture thereof. Limed bone, acid bone, fish
• pig skin gelatins may be used.
• the sheath plasticizer preferably is sorbitol, sorbitol special (a mixture of sorbitol
• the ibuprofen may esterify with the glycerin, reducing the amount
• the non-glycerin plasticizers are preferred.
• the sheath formulations may also contain other ingredients, such as taste
• Taste modifiers include non-reacted ком ⁇ онентs, coloring agents, and moisture retaining agents.
• Taste modifiers include non-reacted ком ⁇ онентs, coloring agents, and moisture retaining agents.
• Taste modifiers include non-reacted ком ⁇ онентs, coloring agents, and moisture retaining agents.
• Taste modifiers include non-reacted ком ⁇ онентs, coloring agents, and moisture retaining agents.
• reducing sugars such as xylitol, maltitol, or Lycasin ® manufactured by Roquette
• Suitable moisture retaining agents include celluloses, cellulose
• the softgel capsule should be of a size
• the fill size of the capsule will be less than 600 mg
• the capsule preferably about 500 mg or less, for the capsule to be of an acceptably small
• the required effective dosage of ibuprofen will normally be at least 175 mg
• the preferred capsules will contain at least
• the overall volume of the fill is also made possible by the fact that only polyethylene
• glycol and polyvinylpyrrolidone are required for dissolution, with a surfactant preferably
• compositions may be free of water and other ingredients that increase the fill volume.
• Examples 1-10 are representative fill
• Examples 11-13 are representative sheath formulations used to encapsulate the fill

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Epidemiology (AREA)
• Pain & Pain Management (AREA)
• Rheumatology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Medicinal Preparation (AREA)
• Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Priority Applications (6)

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Publications (1)

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Family Applications (1)

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Cited By (5)

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Citations (7)

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• 1999
  • 1999-09-02 US US09/389,003 patent/US6251426B1/en not_active Expired - Lifetime
• 2000
  • 2000-09-01 AU AU70949/00A patent/AU780212B2/en not_active Ceased
  • 2000-09-01 DE DE60034044T patent/DE60034044T2/de not_active Expired - Fee Related
  • 2000-09-01 PL PL00362850A patent/PL362850A1/xx not_active Application Discontinuation
  • 2000-09-01 CA CA002382292A patent/CA2382292C/en not_active Expired - Fee Related
  • 2000-09-01 AT AT00959667T patent/ATE357229T1/de not_active IP Right Cessation
  • 2000-09-01 WO PCT/US2000/023908 patent/WO2001015688A1/en not_active Ceased
  • 2000-09-01 JP JP2001519902A patent/JP2003508434A/ja active Pending
  • 2000-09-01 EP EP00959667A patent/EP1207872B1/en not_active Expired - Lifetime

Patent Citations (7)

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