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
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2022—Organic macromolecular compounds
  • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
  • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• • 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
  • A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
• • 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
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2022—Organic macromolecular compounds
  • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
  • A61P7/10—Antioedematous agents; Diuretics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P9/00—Drugs for disorders of the cardiovascular system
  • A61P9/12—Antihypertensives

Definitions

• the invention relates to torasemide-containing pharmaceutical compositions which, for. B. are effective as prophylactic or therapeutic agents against hypertension and edema, or as diuretics.
• Torasemide [chemical name: l-isopropyl-3- (4-m-toluidino-3-pyridyl) sulfonyl) urea] is e.g. B. effective as a diuretic in the context of hypertension therapy.
• Orally administered preparations containing torasemide are produced by a generally customary process by adding, for example, sugar, starch, starch derivatives, cellulose, cellulose derivatives, mold release agents, non-stick agents or other customary auxiliaries; they are applied, for example, as tablets to which lactose, corn starch, silicon oxide or magnesium stearate is added (EP-A-0,212,537).
• compositions are desired in which the storage stability of the torase itself is improved, especially when stored over a longer period of time, changes in the appearance of the preparation caused by moisture absorption are avoided, and the absorption of the torasemide is avoided is further improved by the digestive tract and which have good bioavailability. It has been found that changes in the formulations which have occurred can be caused by corn starch present in the formulation. Accordingly, this invention aims to solve such problems as are encountered in the conventional art and to make better torasemide-containing preparations available for oral administration. To solve the problems described above, numerous commonly used components, such as. B. binders and disintegrants, tests carried out.
• torasemide-containing compositions which contain hydroxypropyl cellulose or polyvinylpyrrolidone (PVP) as binders, sodium croscarmellose or crospovidone as disintegrants and customary shaping agents, such as, for. B. lactose and / or crystalline cellulose and lubricants such as. B. magnesium stearate, have excellent properties as preparations for oral administration.
• PVP polyvinylpyrrolidone
• customary shaping agents such as, for. B. lactose and / or crystalline cellulose and lubricants such as. B. magnesium stearate
• the active ingredient, the binder and the disintegrant are to be used in certain ratios to one another.
• the invention therefore relates to pharmaceutical compositions containing torasemide or a compatible salt thereof, a binder selected from the products hydroxypropyl cellulose and polyvinylpyrrolidone (PVP), a disintegrant selected from the products sodium croscarmellose, crospovidone, calcium carboxymethyl cellulose, contain low-substituted hydroxypropyl cellulose, modified starch and sodium carboxymethyl starch and conventional shaping agents and lubricants.
• PVP polyvinylpyrrolidone
• a disintegrant selected from the products sodium croscarmellose, crospovidone, calcium carboxymethyl cellulose
• torasemide preferably the active ingredient in modification 1
• the torasemide salts are not subject to any particular restriction if they are pharmacologically acceptable substances; as examples, salts with organic acids, such as. B. acetic acid, suberic acid, maleic acid, fumaric acid, malic acid, tartaric acid or methanesulfonic acid, and salts with inorganic acids, such as. As hydrochloric acid, hydrobromic acid, phosphoric acid or sulfuric acid.
• hydroxypropyl cellulose is preferred as the binder; in particular, it was found that especially those with a high degree of substitution are suitable.
• the degree of substitution of such a highly substituted hydroxypropyl cellulose is normally 50-80%, preferably 60-70%, expressed as a content (%) of hydroxypropoxyl groups.
• Commercial hydroxypropyl cellulose is used specifically.
• Polyvinylpyrrolidone is also preferred.
• Sodium croscarmellose, crospovidone, calcium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, modified starch or sodium carboxymethyl starch are preferably used as disintegrants.
• sodium croscarmellose or crospovidones are preferred.
• Sodium croscarmellose is usually understood to mean sodium carboxy ethyl cellulose, crosslinked, crosprovidone polyvinylpyrrolidone, crosslinked.
• a modified starch is preferably a starch converted to the position.
• Shaping agents or lubricants will also be added to the pharmaceutical composition according to this invention; as shaping agents are preferred z.
• the mixing ratio of the individual components in the pharmaceutical composition of this invention is normally 0.1-50 parts (here and hereinafter: parts by weight), preferably 0.5-15 parts, more preferably 1-10 parts of torasemide; 1-10 parts, preferably 2-5 parts binder; 1-20 parts, preferably 3-15 parts, more preferably 5-10 parts of disintegrant.
• the proportions of the other components that are mixed into the pharmaceutical composition of this invention are 10-150 parts, preferably 70-140 parts, more preferably 100-130 parts of shaping agents, and 0.1-5 parts, preferably 0.2-2 Parts, more preferably 0.5-1.5 parts of lubricant.
• the pharmaceutical composition of this invention is e.g. B. as a prophylactic or therapeutic against hypertension and edema, or ideally administered orally as a diuretic.
• the pharmaceutical composition of this invention is processed into a powder, granule, tablet or pellet by conventional methods.
• the application of the pharmaceutical composition according to the invention varies depending on the sex, body weight, age, disease state, etc. of the patient; Usually, a daily dose of approximately 1 to 200 mg of torasemide is administered to an adult, preferably 1 to 30 mg, divided into one to several times a day.
• 40 g torasemide were mixed with 1,064 g lactose, 32 g hydroxypropyl cellulose (content of hydroxypropoxyl groups 62%) and 24 g sodium croscarmellose, pelleted with water, dried and then sieved. 12.9 g of sodium croscarmellose and 3.2 g of magnesium stearate were mixed with 466 g of this substance and the whole was then processed into tablets by a customary process. About 2,300 tablets containing 4 mg of torasemide per tablet were produced in this way.
• the numbers indicate the weight (mg) of the ingredients in the tablet.

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• Health & Medical Sciences (AREA)
• Public Health (AREA)
• Chemical & Material Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Animal Behavior & Ethology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• General Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Epidemiology (AREA)
• Organic Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Diabetes (AREA)
• Hematology (AREA)
• Cardiology (AREA)
• Heart & Thoracic Surgery (AREA)
• Medicinal Preparation (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (3)

Publications (1)

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• 1991
  • 1991-06-25 JP JP18182091A patent/JP3586471B2/ja not_active Expired - Lifetime
• 1992
  • 1992-06-25 WO PCT/EP1992/001437 patent/WO1993000097A1/de not_active Application Discontinuation
  • 1992-06-25 EP EP92913781A patent/EP0591363A1/de not_active Withdrawn

Non-Patent Citations (1)

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