WO2001047494A1 - Procede de co-broyage de substances et de lactose au moyen d'un broyeur a jet fluide - Google Patents

Procede de co-broyage de substances et de lactose au moyen d'un broyeur a jet fluide Download PDF

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Publication number
WO2001047494A1
WO2001047494A1 PCT/EP2000/012569 EP0012569W WO0147494A1 WO 2001047494 A1 WO2001047494 A1 WO 2001047494A1 EP 0012569 W EP0012569 W EP 0012569W WO 0147494 A1 WO0147494 A1 WO 0147494A1
Authority
WO
WIPO (PCT)
Prior art keywords
substance
lactose
grinding
micronized
pyrazolo
Prior art date
Application number
PCT/EP2000/012569
Other languages
German (de)
English (en)
Inventor
Tobias Laich
Original Assignee
Bayer Aktiengesellschaft
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 Bayer Aktiengesellschaft filed Critical Bayer Aktiengesellschaft
Priority to AU25104/01A priority Critical patent/AU2510401A/en
Publication of WO2001047494A1 publication Critical patent/WO2001047494A1/fr

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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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
    • 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

Definitions

  • the present application relates to a process for co-grinding substances and lactose in jet mills and the micronized substance-lactose mixtures obtainable therewith.
  • This process step increases the surface of the fabric and can e.g. increase the dissolution rate or bioavailability of active substances in the manufacture of pharmaceuticals.
  • the surface of the active ingredient can also influence the release profile (EP-A-047899). These parameters are of great interest for the drug formulation.
  • the comminution (micronization) of the substances is carried out in gas jet mills, e.g. in spiral jet or fluidized bed counter jet mills.
  • lactose milk sugar
  • co-grinding joint micronization of the substance-lactose mixture
  • the substance is mixed with lactose in a ratio of 100: 10 - 85 (w / w).
  • Mixing of the substance with lactose in a ratio of 100: 15-60 (w / w) is preferred, particularly preferably 100: 20 -50 (w / w).
  • the advantages of the reduced material structure according to the invention do not have.
  • metal abrasion often occurs with other materials, such as calcium phosphate, which leads to discoloration of the ground product. This is unacceptable when manufacturing drugs or food.
  • the lactose has the advantage that it is pharmaceutically harmless and easily removable from the micronized mixture in the case of non-water-soluble substances, which is important in process control e.g. is advantageous for particle size measurement.
  • the properties of tablets made from microfine mixtures, such as compactibility or tablet disintegration, are not adversely affected by lactose.
  • the starting particle size of the lactose is practically without influence in the process according to the invention: particles with an average particle size distribution (volume distribution) of 75 ⁇ m to 300 ⁇ m are preferred.
  • substances are micronized in which 90% or more have a size of less than or equal to 25 ⁇ m. The percentage refers to the number of particles.
  • the method according to the invention for co-grinding is basically suitable for all
  • the substances to be micronized are active ingredients, in particular cardiovascular agents and in particular substituted pyrazole derivatives such as 5-cyclopropyl-2- [1 - (2-fluoro-benzyl) -1 H-pyrazolo [3, 4 -b] pyridin-3-yl] -pyrimidin-4-ylamine or 2- [1 - (2-fluoro-benzyl) -lH-pyrazolo [3,4-b] pyridin-3-yl] -5-mo ⁇ holin- 4-yl-pyrimidine-4,6-diamine.
  • active ingredients in particular cardiovascular agents and in particular substituted pyrazole derivatives such as 5-cyclopropyl-2- [1 - (2-fluoro-benzyl) -1 H-pyrazolo [3, 4 -b] pyridin-3-yl] -pyrimidin-4-ylamine or 2- [1 - (2-fluoro-benzyl) -lH-pyrazolo [3,4-
  • the mixture to be micronized can of course be admixed with other substances which do not negatively influence the co-grinding behavior.
  • auxiliaries of pharmaceutical technology are added, such as disintegrants, lubricants, matrix formers,
  • the fineness and surface of the ground material can be adjusted.
  • the present invention furthermore relates to compositions for oral administration, containing micronized active ingredient and micronized lactose, in particular tablets and enteric-coated tablets, ⁇ art capsules, soft capsules, dragees, pills, granules, pellets, powders and suspensions. All drug forms mentioned can also be modified in their release behavior by coatings or additives.
  • Active ingredient A 100.00 68.42% 136.84 crystalline
  • micronized mixture is mixed with 0.49 g of sodium lauryl sulfate (Texapon, from Henkel, Germany) and 5.95 g of sodium carboxymethyl cellulose (Ac-Di-Sol, from FMC, United States) and 1.98 g of magnesium stearate (from. Greven, Germany) and mixed again for 5 min in a turbulami mixer (30 rpm). The mixture is then compressed into tablets (146.16 mg tablet weight).
  • sodium lauryl sulfate Texapon, from Henkel, Germany
  • sodium carboxymethyl cellulose Ac-Di-Sol, from FMC, United States
  • magnesium stearate from. Greven, Germany
  • Active ingredient B 100.00 58.82% 29.41 crystalline
  • micronized The micronized mixture is mixed with 6.85 g of microcrystalline cellulose (Avicel P ⁇ 1010, from FMC, United States) and 1.47 g of sodium carboxymethyl cellulose (Ac-Di-Sol, from FMC, United States) and 0.5 g of magnesium stearate (from . Greven, Germany) and again for 5 min in
  • Active ingredient A 100.00 79.26% 158.53 crystalline
  • Active ingredient B 100.00 66.67% 33.33 crystalline
  • micronized The micronized mixture is mixed with 7.77 g of microcrystalline cellulose (Avicel P ⁇ 1010, from FMC, United States) and 1.67 g of sodium carboxymethyl cellulose (Ac-Di-Sol, from FMC, United States) and 0.57 g of magnesium stearate ( Greven, Germany) and again for 5 min
  • Active ingredient A 100.00 68.42% 410.52 crystalline
  • active ingredient A 136.84 g of active ingredient A are mixed with 54.73 g of Emcompress (calcium phosphate dihydrate, from Mendell, United States) in a Turbula mixer for 10 min at 30 rpm. The mixture is then milled with an LSM 50 spiral jet mill (stainless steel version, 50 mm grinding chamber, 0.85 mm injector nozzle, 0.75 mm grinding nozzles, 14 mm outlet disc, 2.5 mm Teflon catch nozzle with nitrogen.
  • Emcompress calcium phosphate dihydrate, from Mendell, United States
  • the micronized mixture is 0.49 g
  • 200.0 g of active ingredient A are milled with nitrogen using an LSM 50 spiral jet mill (stainless steel version, 50 mm grinding chamber, 0.85 mm injector nozzle, 0.75 mm grinding nozzle, 14 mm outlet disc, 2.5 mm Teflon catch nozzle. Injector pressure 5 bar, grinding pressure 4.5 bar. grinding time approx. 25 min) micronized.
  • LSM 50 spiral jet mill stainless steel version, 50 mm grinding chamber, 0.85 mm injector nozzle, 0.75 mm grinding nozzle, 14 mm outlet disc, 2.5 mm Teflon catch nozzle.
  • Injector pressure 5 bar, grinding pressure 4.5 bar. grinding time approx. 25 min) micronized.

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

Abstract

L'invention concerne un procédé de co-broyage de substances et de lactose dans un broyeur à jet fluide, ainsi que le mélange de substances-lactose micronisé ainsi obtenu.
PCT/EP2000/012569 1999-12-24 2000-12-12 Procede de co-broyage de substances et de lactose au moyen d'un broyeur a jet fluide WO2001047494A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU25104/01A AU2510401A (en) 1999-12-24 2000-12-12 Method for co-grinding substances and lactose by means of jet mils

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19962926.9 1999-12-24
DE19962926A DE19962926A1 (de) 1999-12-24 1999-12-24 Verfahren zur Co-Mahlung von Stoffen und Lactose mittels Strahlmühlen

Publications (1)

Publication Number Publication Date
WO2001047494A1 true WO2001047494A1 (fr) 2001-07-05

Family

ID=7934436

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/012569 WO2001047494A1 (fr) 1999-12-24 2000-12-12 Procede de co-broyage de substances et de lactose au moyen d'un broyeur a jet fluide

Country Status (3)

Country Link
AU (1) AU2510401A (fr)
DE (1) DE19962926A1 (fr)
WO (1) WO2001047494A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017106175A2 (fr) 2015-12-14 2017-06-22 Ironwood Pharmaceuticals, Inc. Utilisation de stimulateurs de la sgc pour le traitement d'un dysfonctionnement du sphincter gastro-intestinal
WO2018111795A2 (fr) 2016-12-13 2018-06-21 Ironwood Pharmaceuticals, Inc. Utilisation de stimulateurs de sgc pour le traitement de la motilité œsophagienne
WO2020014504A1 (fr) 2018-07-11 2020-01-16 Cyclerion Therapeutics, Inc. Utilisation de stimulateurs gcs pour le traitement de maladies mitochondriales

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006086270A1 (fr) 2005-02-10 2006-08-17 Glaxo Group Limited Procedes de fabrication du lactose au moyen de techniques de pre-classification et preparations pharmaceutiques ainsi obtenues

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998031352A1 (fr) * 1997-01-20 1998-07-23 Astra Aktiebolag Nouvelle formulation pour inhalation ayant une masse volumique apparente de 0,28 a 0,38 g/ml, procede de preparation et utilisation de cette formulation
EP1048295A2 (fr) * 1999-04-27 2000-11-02 SHERMAN, Bernard Charles Compositions pharmaceutiques contenant du fénofibrate co-micronisé

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998031352A1 (fr) * 1997-01-20 1998-07-23 Astra Aktiebolag Nouvelle formulation pour inhalation ayant une masse volumique apparente de 0,28 a 0,38 g/ml, procede de preparation et utilisation de cette formulation
EP1048295A2 (fr) * 1999-04-27 2000-11-02 SHERMAN, Bernard Charles Compositions pharmaceutiques contenant du fénofibrate co-micronisé

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017106175A2 (fr) 2015-12-14 2017-06-22 Ironwood Pharmaceuticals, Inc. Utilisation de stimulateurs de la sgc pour le traitement d'un dysfonctionnement du sphincter gastro-intestinal
WO2018111795A2 (fr) 2016-12-13 2018-06-21 Ironwood Pharmaceuticals, Inc. Utilisation de stimulateurs de sgc pour le traitement de la motilité œsophagienne
WO2020014504A1 (fr) 2018-07-11 2020-01-16 Cyclerion Therapeutics, Inc. Utilisation de stimulateurs gcs pour le traitement de maladies mitochondriales

Also Published As

Publication number Publication date
AU2510401A (en) 2001-07-09
DE19962926A1 (de) 2001-06-28

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