WO2000025750A1 - Compositions de metamizole a liberation prolongee - Google Patents

Compositions de metamizole a liberation prolongee Download PDF

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Publication number
WO2000025750A1
WO2000025750A1 PCT/EP1999/008120 EP9908120W WO0025750A1 WO 2000025750 A1 WO2000025750 A1 WO 2000025750A1 EP 9908120 W EP9908120 W EP 9908120W WO 0025750 A1 WO0025750 A1 WO 0025750A1
Authority
WO
WIPO (PCT)
Prior art keywords
controlled
metamizole
release tablets
fatty
tablets according
Prior art date
Application number
PCT/EP1999/008120
Other languages
English (en)
Inventor
Mauro Valenti
Flavio Fabiani
Original Assignee
Farmaceutici Formenti S.P.A.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Farmaceutici Formenti S.P.A. filed Critical Farmaceutici Formenti S.P.A.
Priority to AU11550/00A priority Critical patent/AU1155000A/en
Publication of WO2000025750A1 publication Critical patent/WO2000025750A1/fr

Links

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
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • 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
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • 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

  • Metamizole or [2 , 3-dihydro-l , 5 -dimethyl -3 -oxo-2- phenyl-lH-pyrazol-4-yl) -methylamino] methane sulfonic acid sodium or magnesium salt is an orally active analgesic .
  • Metamizole has been commercially available for a long time in the form of conventional pharmaceutical compositions such as tablets, drops, suppositories and the like, as an analgesic and antipyretic. Controlled- release formulations of metamizole have never been disclosed.
  • the present invention provides therefore controlled release tablets comprising: a) metamizole, or its pharmaceutically acceptable salt as the active ingredient, coated by a fatty compound ; b) an hydrophilic water swellable polymer; c) suitable excipients.
  • the fatty compound consists of hydrophobic high molecular weight compounds, preferably waxes, triglycerides of long chain fatty acids, vegetable or mineral oils, fatty acids, high molecular weight alcohols or glycols, esters and ethers thereof. It is preferred the use of compounds having a melting point ranging from at least 30 to 150°C. Glyceryl behenate is particularly preferred.
  • suitable hydrophilic polymers include polyethylenglycols, alginates, cellulose and its derivatives (ethers, esters, salts) , acrylic acid polymers or co-polymers. Hydroxypropylcellulose is particularly preferred. Conventional excipients, commonly used in the preparation of oral solid dosage forms, can be added to the compositions of the invention.
  • excipients include lubricants, diluents, disgregating agents, colouring agents, etc.
  • Each tablet will typically contain from 200 to 1500 mg of active ingredient.
  • the percentage of the fatty compound in the mixture with metamizole will range from about 2 to about 40% by weight, preferably from about 5 to 15%.
  • the percentage of the hydrophilic polymer ranges from 5 to 50% of the weight of the active ingredient, preferably from 10 to 40%.
  • the invention also relates to multi-layer tablets, preferably double-layer tablets, in which one of the layers has a controlled release and one of the others has an immediate release.
  • compositions of the invention may be prepared by a process comprising: a) subjecting metamizole and the fatty compound to melt granulation; b) mixing the granulate obtained in a) with an hydrophilic compound and suitable excipients; c) tabletting the mixture obtained in b) .
  • the melt granulation step is carried out by heating the mixture to the melting point of the fatty compound in a fluid bed, a static oven or a conventional granulating apparatus.
  • the tablets may be film-coated in order to provide taste-masking or a further enhancement of the release characteristics .
  • the release characteristics of the composition may be changed by adjusting the ratio of the fatty compound to the hydrophilic polymer.
  • the in vitro release may range, for instance, from 6-8 up to 24 hours.
  • compositions of the invention may be accordingly administered twice or even once a day, according to the desired therapeutic needs.
  • compositions of the invention are moreover characterized by a remarkable stability, possibly in view of the protective effect the fatty compound exerts on the water-instable active ingredient.
  • each tablet contains:
  • a melt granulation process is carried out with a high speed granulator mixing Metamizole and glyceryl behenate.
  • the obtained granulate is mixed thereafter with the other excipients and tabletted.
  • the in vitro release profile is shown. The test was carried out in water, 1000 ml, stirring speed 50 rpm, 37°C, UV detection at 300 nm.
  • each tablet contains:
  • each tablet contains :
  • each tablet contains: Sodium Metamizole Monohydrate mg 1000. ,0 Cetyl alcohol mg 80. ,0
  • each tablet contains:
  • each tablet contains:
  • each tablet contains:
  • Example 8 each tablet contains: Sodium Metamizole Monohydrate mg 1000.0
  • each tablet contains:
  • Acrylic Acid Co-polymers mg 120.0 The preparation method and the determination of the in vitro release were carried out as in Example 1.
  • each tablet contains:
  • Microcrystalline Cellulose mg 40 . 0 Colloidal Silica mg 6 , . 5
  • each tablet contains:
  • each tablet contains:
  • Example 11 The preparation method of Example 11 was followed, using a first tabletting step followed by sieving and then by a second tabletting step. The amount of magnesium stearate is portioned into two equal parts. Time (hours) (%) Released
  • each tablet contains: Sodium Metamizole Monohydrate mg 1000 . . 0
  • Example 14 each tablet contains:
  • Titanium bioxide mg 2 .0 The melt granulation process is carried out with a high speed granulator mixing Metamizole and glyceryl behenate. The obtained granulate is mixed thereafter with the other excipients and tabletted.
  • the film composition is the one referred to as the coating, the aim being masking the taste without changing the release profile .
  • each tablet contains:
  • the melt granulation process is carried out with a high speed granulator mixing Metamizole and glyceryl behenate. The obtained granulate is mixed thereafter with the other excipients and tabletted.
  • Magnesium stearate mg 2.0 Metamizole is mixed with the other excipients.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Rheumatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pain & Pain Management (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)
  • Macromonomer-Based Addition Polymer (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Compositions solides à libération prolongée pour administration orale, obtenues en soumettant le principe actif et un composé gras à la granulation par fusion, puis en mélangeant le granulat obtenu avec un polymère hydrophile et des excipients classiques.
PCT/EP1999/008120 1998-11-03 1999-10-27 Compositions de metamizole a liberation prolongee WO2000025750A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU11550/00A AU1155000A (en) 1998-11-03 1999-10-27 Controlled-release formulations of metamizole

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITMI98A002365 1998-11-03
IT1998MI002365A IT1303693B1 (it) 1998-11-03 1998-11-03 Composizioni a rilascio controllato di metamizolo.

Publications (1)

Publication Number Publication Date
WO2000025750A1 true WO2000025750A1 (fr) 2000-05-11

Family

ID=11380995

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1999/008120 WO2000025750A1 (fr) 1998-11-03 1999-10-27 Compositions de metamizole a liberation prolongee

Country Status (6)

Country Link
AR (1) AR020998A1 (fr)
AU (1) AU1155000A (fr)
CO (1) CO5160319A1 (fr)
IT (1) IT1303693B1 (fr)
PE (1) PE20001231A1 (fr)
WO (1) WO2000025750A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000066088A1 (fr) * 1999-05-04 2000-11-09 Hexal Ag Composition pharmaceutique a liberation controlee contenant du metamizol
US20110046072A1 (en) * 2008-05-07 2011-02-24 Bayer Animal Health Gmbh Solid pharmaceutical formulation with delayed release
WO2018087109A1 (fr) 2016-11-08 2018-05-17 Grünenthal GmbH Forme galénique multiparticulaire à libération de métamizole contrôlée
US10682337B2 (en) * 2015-03-03 2020-06-16 Kindred Biosciences, Inc. Compositions and methods for treatment and prevention of pyrexia in horses

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998047534A1 (fr) * 1997-04-18 1998-10-29 Klinge Pharma Gmbh Medicaments stabilises renfermant des derives cysteinyle

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998047534A1 (fr) * 1997-04-18 1998-10-29 Klinge Pharma Gmbh Medicaments stabilises renfermant des derives cysteinyle

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 91, no. 10, 3 September 1979, Columbus, Ohio, US; abstract no. 78844, XP002110962 *
L.V.N.PRISTA ET AL.: "COMPRESSED DIPYRONE TABLETS WITH PROLONGED ACTION", AN. FAC. FARM. UNIV. FED. PERNAMBUCO (BR), vol. 15, 1976, pages 57 - 68 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000066088A1 (fr) * 1999-05-04 2000-11-09 Hexal Ag Composition pharmaceutique a liberation controlee contenant du metamizol
US20110046072A1 (en) * 2008-05-07 2011-02-24 Bayer Animal Health Gmbh Solid pharmaceutical formulation with delayed release
US10682337B2 (en) * 2015-03-03 2020-06-16 Kindred Biosciences, Inc. Compositions and methods for treatment and prevention of pyrexia in horses
WO2018087109A1 (fr) 2016-11-08 2018-05-17 Grünenthal GmbH Forme galénique multiparticulaire à libération de métamizole contrôlée

Also Published As

Publication number Publication date
AU1155000A (en) 2000-05-22
CO5160319A1 (es) 2002-05-30
PE20001231A1 (es) 2000-11-29
AR020998A1 (es) 2002-06-05
ITMI982365A1 (it) 2000-05-03
IT1303693B1 (it) 2001-02-23

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