EP0859600A1 - New technology for wet granulation - Google Patents

New technology for wet granulation

Info

Publication number
EP0859600A1
EP0859600A1 EP96934274A EP96934274A EP0859600A1 EP 0859600 A1 EP0859600 A1 EP 0859600A1 EP 96934274 A EP96934274 A EP 96934274A EP 96934274 A EP96934274 A EP 96934274A EP 0859600 A1 EP0859600 A1 EP 0859600A1
Authority
EP
European Patent Office
Prior art keywords
active ingredient
solubility
electrolyte
compound
wet granulation
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
EP96934274A
Other languages
German (de)
English (en)
French (fr)
Inventor
Simon Bechard
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.)
Merck Frosst Canada and Co
Original Assignee
Merck Frosst Canada and Co
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
Priority claimed from GBGB9604277.5A external-priority patent/GB9604277D0/en
Application filed by Merck Frosst Canada and Co filed Critical Merck Frosst Canada and Co
Publication of EP0859600A1 publication Critical patent/EP0859600A1/en
Ceased legal-status Critical Current

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
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient

Definitions

  • This invention is concerned with a novel method of wet granulation in the manufacture of tablets comprising a large dose of a highly soluble compound as active ingredient.
  • the novel method comprises the addition of a second compound having the capability of decreasing solubility of the active ingredient prior to agglomeration.
  • the invention is particularly concerned with the novel method wherein the active ingredient is a highly soluble ionic compound.
  • the novel method of this invention is a wet granulation of an active ingredient which is a highly soluble compound and is to be inco ⁇ orated in a relatively high concentration in compressed tablets which comprises the addition of a second compound to reduce the solubility of the active ingredient prior to the agglomeration step.
  • the solubility of the active ingredient is decreased and a signficant increase in the viscosity of the granulation is adequately suppressed.
  • This novel method is particularly useful wherein the active ingredient is ionic and has an aqueous solubility of about 10 to about 500 mg/ml, especially about 135 to about 235 mg/ml of water.
  • the second compound added during the novel process is ordinarily a soluble ionic compound that can suppress the solubility of the active ingredient especially an electrolyte having an ion in common with that of the active ingredient.
  • the tablet compositions prepared by the novel method of this invention are generally art recognized and employ standard excipients based on their compatibility with one another and with the active ingredient .
  • excipients are such as: microcrystalline cellulose, dextrates, calcium phosphates, or pregelatinized starch for their compactibility properties, lactose, mannitol, sorbitol, xylitol, sucrose or glucose because of their water solubility which improves the agglomeration process; hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinly pyrrolidone as binders or adhesives; Croscarmelose, crospovidone or sodium starch glycolate as disintegrants; and lastly, magnesium or calcium stearate, stearic acid, sodium stearyl fumarate, or polyethylene glycols as lubricants; and a granulating fluid such as water or ethanol: water mixtures.
  • the active agent is dry blended with the excipients, and an aqueous solution of the second compound is atomized onto the blend.
  • the blend is then granulated by spraying onto it an aqueous solution of the granulating fluid, which may or may not contain the binder. After drying, the granulation is sized, lubricated with magnesium stearate and then compressed to form the tablet cores.
  • the active ingredient in the following Example is identified as montelukast sodium. This name is listed in USAN and is used by T.R. Jones, et al in Can. J. Physiol. Pharmacol.. (1995) 73(2), 191-201. It has the name and absolute structural formula as follows:
  • Sodium chloride was dissolved in 540 g of water. Hydroxypropyl cellulose was dissolved in 1485 g of water. The microcrystalline cellulose, montelukast sodium, lactose hydrous and Croscarmellose were added together and blended for 5 minutes. The sodium chloride solution was added over 30 seconds and blended for 30 seconds. The hydroxypropylcellulose solution was sprayed onto the mixture over 1.5 minutes and mixed for 30 seconds. After drying, the granulation was sized and then lubricated by addition of the magnesium stearate. The lubricated blend was then compressed to form tablet cores.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Manufacturing Of Micro-Capsules (AREA)
EP96934274A 1995-11-02 1996-10-31 New technology for wet granulation Ceased EP0859600A1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US616195P 1995-11-02 1995-11-02
US6161P 1995-11-02
GB9604277 1996-02-29
GBGB9604277.5A GB9604277D0 (en) 1996-02-29 1996-02-29 New technology for wet granulation
PCT/CA1996/000724 WO1997016173A1 (en) 1995-11-02 1996-10-31 New technology for wet granulation

Publications (1)

Publication Number Publication Date
EP0859600A1 true EP0859600A1 (en) 1998-08-26

Family

ID=26308826

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96934274A Ceased EP0859600A1 (en) 1995-11-02 1996-10-31 New technology for wet granulation

Country Status (5)

Country Link
EP (1) EP0859600A1 (ja)
JP (1) JPH11514382A (ja)
AU (1) AU709301B2 (ja)
CA (1) CA2236175A1 (ja)
WO (1) WO1997016173A1 (ja)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MY148466A (en) * 2001-10-26 2013-04-30 Merck Frosst Canada Ltd Granule formulation
CZ298224B6 (cs) * 2003-04-29 2007-07-25 Pliva Istrazivanje I Razvoj D.O.O. Farmaceutická kompozice obsahující jako úcinnou látku ribavirin a zpusob její výroby
SI1976522T2 (sl) 2005-12-30 2019-11-29 Krka Tovarna Zdravil D D Novo Mesto Farmacevtski sestavek, ki vsebuje montelukast
KR101278572B1 (ko) * 2011-10-18 2013-06-25 주식회사 네비팜 류코트리엔 길항제와 에피나스틴의 복합제제
WO2014012954A1 (en) 2012-07-18 2014-01-23 Takeda Gmbh Treatment of partly controlled or uncontrolled severe asthma
CA2936332A1 (en) 2014-01-22 2015-07-30 Takeda Gmbh Treatment of partly controlled or uncontrolled severe asthma with a pde4 inhibitor (and in combination with a leukotriene modifier)
EP2949321A1 (en) 2014-05-26 2015-12-02 Sanovel Ilac Sanayi ve Ticaret A.S. Multilayer formulations of fexofenadine and montelukast
WO2017182644A1 (en) 2016-04-22 2017-10-26 Sanovel Ilac Sanayi Ve Ticaret A.S. Tablet formulations of montelukast sodium and rupatadine fumarate
WO2017182641A1 (en) 2016-04-22 2017-10-26 Sanovel Ilac Sanayi Ve Ticaret A.S. Bilayer tablet formulations of montelukast and rupatadine

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5350584A (en) * 1992-06-26 1994-09-27 Merck & Co., Inc. Spheronization process using charged resins

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9716173A1 *

Also Published As

Publication number Publication date
CA2236175A1 (en) 1997-05-09
AU7274196A (en) 1997-05-22
AU709301B2 (en) 1999-08-26
WO1997016173A1 (en) 1997-05-09
JPH11514382A (ja) 1999-12-07

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Legal Events

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