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WO2014067501A1 - Comprimés dispersibles contenant du déférasirox - Google Patents

Comprimés dispersibles contenant du déférasirox Download PDF

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Publication number
WO2014067501A1
WO2014067501A1 PCT/CZ2013/000138 CZ2013000138W WO2014067501A1 WO 2014067501 A1 WO2014067501 A1 WO 2014067501A1 CZ 2013000138 W CZ2013000138 W CZ 2013000138W WO 2014067501 A1 WO2014067501 A1 WO 2014067501A1
Authority
WO
WIPO (PCT)
Prior art keywords
disintegrant
pharmaceutically acceptable
dispersible tablet
tablet according
deferasirox
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/CZ2013/000138
Other languages
English (en)
Inventor
Cyrus Victor SKARIA
Malgorzata Stokrocka
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zentiva KS
Original Assignee
Zentiva KS
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 Zentiva KS filed Critical Zentiva KS
Publication of WO2014067501A1 publication Critical patent/WO2014067501A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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
    • A61K31/33—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
    • A61K31/4196—1,2,4-Triazoles
    • 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
    • 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

Definitions

  • the present invention relates to dispersible tablets containing 4-[3,5-bis(2-hydroxyphenyl)- lH-[l,2,4]triazol-l-yl]benzoic acid or its pharmaceutically acceptable salts or crystalline forms and a combination of at least two disintegrants that have the same or different chemical composition and a different average size of particles while the total amount of the disintegrant in a tablet is more than 35% by weight.
  • Deferasirox is an orally active iron chelator that is indicated for treatment of iron overload in patients with anemia treated by blood transfusions, in specific cases for beta thalassemia, thalassemia intermedia and for sickle cell anemia to reduce morbidity and mortality caused by iron, and is also used to treat haemochromatosis.
  • the patent application WO2004/035026A describes dispersible tablets containing 5 to 40% by weight of deferasirox or its pharmaceutically acceptable salts and at least one disintegrant in the amount of 10% to 35% by weight.
  • the dispersible tablets are preferably prepared by wet granulation, which improves the physical characteristics of the drug, or the active substance, respectively, especially its poor flowability and sticking tendency.
  • the description emphasizes that even with the use of wet granulation the active component keeps sticking and is difficult to handle during tabletting.
  • This problem was solved by adding a lubricant to the tabletting mixtures.
  • a lubricant in amounts exceeding 0.2% by weight made the disintegration of dispersible tablets longer than 3 minutes. For this reason the lubricant is not added to the mixture, but is directly sprayed onto the punches of the tabletting machine in amounts lower than 0.2% by weight in order to meet the requirement of the European Pharmacopoeia for disintegration, which should be shorter than 3 minutes.
  • dispersible tablets containing deferasirox a combination of at least two disintegrants that have the same or different chemical composition and a different average size of particles, while the total amount of the disintegrant in a tablet is more than 35% by weight, and one or more pharmaceutically acceptable excipients have reduced the disintegration time of tablets and exhibited acceptable hardness and abrasion.
  • a lubricant added in an amount of up to 2% by weight has no significant impact on the disintegration time of the tablet and improves processability of the active substance and excipients.
  • the present invention provides a dispersible tablet containing deferasirox, its pharmaceutically acceptable salts or crystalline forms, a combination of at least two disintegrants that have the same or different chemical composition and a different average size of particles, the total amount of the disintegrant in the a tablet being more than 35% by weight, and one or more pharmaceutically acceptable excipients.
  • the dispersible tablet contains a combination of at least two disintegrants that have the same or different chemical composition where the average particle size of the first disintegrant is less than 75 ⁇ and the average particle size of the other disintegrant is more than 75 ⁇ and less than 400 ⁇ , preferably, the particle size of the first disintegrant is smaller than 50 ⁇ , preferably smaller than 15 ⁇ and the average particle size of the other disintegrant is from 100 ⁇ to 400 ⁇ , preferably from 110 ⁇ to 140 ⁇ .
  • the dispersible tablet contains deferasirox, its pharmaceutically acceptable salts or crystalline forms in an amount of from 15% by weight to 40% by weight.
  • the tablet preferably contains 25 - 35% by weight of deferasirox, its pharmaceutically acceptable salt or crystalline form.
  • the dispersible table contains the first and second disintegrant in a total amount of from 40% by weight to 58% by weight.
  • the first disintegrant with the particle size of less than 75 um is crospovidone, sodium starch glycolate, corn starch, sodium crosscarmellose or low-substituted hydroxypropyl cellulose.
  • the average particle size of examples of suitable disintegrants is presented in the table below.
  • the other disintegrant exhibiting an average particle size of more than 75 ⁇ and less than 400 ⁇ is crospovidone.
  • suitable variants of crospovidone with average particle sizes are presented in the table below.
  • the dispersible tablet further contains one or more pharmaceutically acceptable excipients comprising fillers, wetting agents, glidants and lubricants.
  • Suitable wetting agents are sodium lauryl sulphate, polysorbates, poloxamer, quaternary ammonium salts or any combinations thereof.
  • the average particle size of the first disintegrant is 75 ⁇ , preferably less than 50 ⁇ , most preferably less than 15 ⁇ , and the average particle size of the other disintegrant is from 75 ⁇ to 400 ⁇ , preferably from 100 ⁇ to 400 ⁇ , most preferably from 110 ⁇ to 140 ⁇ .
  • the dispersible tablets have a two-phase structure consisting of:
  • the disintegration time of the dispersible tablets in aqueous solutions is shorter than 3 minutes.
  • Crospovidone Polyplasdone XL 8.89
  • Crospovidone (Kollidon CL-M) 2.95
  • Example 3c Dispersible tablet formulation containing 1.99% by weight of magnesium stearate:

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne des comprimés dispersibles contenant un acide 4-[3,5-bis (2-hydroxyphényl)-1H-[1,2,4]triazol-1-yl] benzoïque (déférasirox), ou ses sels pharmaceutiquement acceptables ou formes cristallines, et une combinaison d'au moins deux désagrégeants présentant une composition chimique identique ou différente et des tailles de particules moyennes différentes, la quantité totale du désagrégeant dans le comprimé étant supérieure à 35 % en poids.
PCT/CZ2013/000138 2012-10-31 2013-10-25 Comprimés dispersibles contenant du déférasirox Ceased WO2014067501A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CZ2012-743A CZ2012743A3 (cs) 2012-10-31 2012-10-31 Dispergovatelné tablety obsahující deferasirox
CZPV2012-743 2012-10-31

Publications (1)

Publication Number Publication Date
WO2014067501A1 true WO2014067501A1 (fr) 2014-05-08

Family

ID=49641429

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CZ2013/000138 Ceased WO2014067501A1 (fr) 2012-10-31 2013-10-25 Comprimés dispersibles contenant du déférasirox

Country Status (2)

Country Link
CZ (1) CZ2012743A3 (fr)
WO (1) WO2014067501A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016114624A3 (fr) * 2015-01-16 2016-09-09 대원제약주식회사 Suspension contenant du déférasirox
WO2019151967A3 (fr) * 2017-12-29 2019-10-17 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Formulations de comprimés dispersibles dans l'eau comprenant du déférasirox

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090142395A1 (en) * 2007-11-19 2009-06-04 Uri Zadok Deferasirox pharmaceutical compositions
WO2012003987A1 (fr) * 2010-07-08 2012-01-12 Ratiopharm Gmbh Forme posologique orale de déférasirox

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090142395A1 (en) * 2007-11-19 2009-06-04 Uri Zadok Deferasirox pharmaceutical compositions
WO2012003987A1 (fr) * 2010-07-08 2012-01-12 Ratiopharm Gmbh Forme posologique orale de déférasirox

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ROWE ET AL.: "Handbook of Pharmaceutical Excipients Fourth Edition", 26 November 2002, PUBLISHER - SCIENCE AND PRACTICE, ROYAL PHARMACEUTICAL SOCIETY OF GREAT BRITAIN, London, UK, article "Cellulose, Microcrystalline", pages: 108 - 111, XP002719369 *
ROWE ET AL.: "Handbook of Pharmaceutical Excipients Fourth Edition", 26 November 2002, PUBLISHER - SCIENCE AND PRACTICE, ROYAL PHARMACEUTICAL SOCIETY OF GREAT BRITAIN, London, Uk, article "Crospovidone", pages: 184 - 184, XP002719370 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016114624A3 (fr) * 2015-01-16 2016-09-09 대원제약주식회사 Suspension contenant du déférasirox
WO2019151967A3 (fr) * 2017-12-29 2019-10-17 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Formulations de comprimés dispersibles dans l'eau comprenant du déférasirox

Also Published As

Publication number Publication date
CZ2012743A3 (cs) 2014-05-07

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