WO2010043376A1 - Comprimés contenant du valsartan - Google Patents

Comprimés contenant du valsartan Download PDF

Info

Publication number
WO2010043376A1
WO2010043376A1 PCT/EP2009/007347 EP2009007347W WO2010043376A1 WO 2010043376 A1 WO2010043376 A1 WO 2010043376A1 EP 2009007347 W EP2009007347 W EP 2009007347W WO 2010043376 A1 WO2010043376 A1 WO 2010043376A1
Authority
WO
WIPO (PCT)
Prior art keywords
valsartan
active ingredient
pharmaceutically acceptable
acceptable salt
powder
Prior art date
Application number
PCT/EP2009/007347
Other languages
German (de)
English (en)
Inventor
Peng Junqing
Zhou Shilin
Gao Huiyan
Hu Gongyun
Original Assignee
Alfred E. Tiefenbacher Gmbh & Co. Kg
Huahai
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 Alfred E. Tiefenbacher Gmbh & Co. Kg, Huahai filed Critical Alfred E. Tiefenbacher Gmbh & Co. Kg
Priority to EP09736570A priority Critical patent/EP2349215A1/fr
Publication of WO2010043376A1 publication Critical patent/WO2010043376A1/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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5084—Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs
    • 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
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/549—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
    • 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 a process for producing a valsartan-containing tablet. Furthermore, the invention relates to an active ingredient granules which consists exclusively of valsartan or a pharmaceutically acceptable salt thereof and optionally another active ingredient, as well as its use in the preparation of a tablet containing valsartan.
  • Valsartan is an angiotensin II receptor antagonist and is mainly used for the treatment of hypertension and mild to moderate heart failure.
  • Valtartan containing film-coated tablets of the strengths 40 mg, 80 mg and 160 mg are marketed under the trade names Diovan or Cordinate.
  • the active substance combination valsartan / hydrochlorothiazide (HCT) containing film-coated tablets of the strengths 80 mg / 12.5 mg, 160 mg / 12.5 mg, 160 mg / 25 mg, 320 mg / 12.5 mg and 320 mg / 25 mg are administered under Trade name Co-Diovan ® marketed.
  • Valsartan is obtained in its preparation as a powder which has a low bulk density, which can lead to problems in tabletting, since tabletting machines usually dose volumetrically and, as a result, variations in the dosage can occur. In addition, has powdered Valsartan poor flow properties, which makes it difficult to produce tabletting mixtures.
  • WO 97/49394 proposes to grind valsartan and pharmaceutically acceptable excipients and to prepare a mixture thereof, which is subsequently subjected to a dry granulation process by compacting the mixture, preferably with compacting rollers, and then granulating the resulting compact or Schülpe. The granules are then pressed into the tablet.
  • the compaction be carried out at a minimum pressing force so that the granules can disintegrate into its primary particles at a sufficiently high rate when it comes in contact with the surrounding liquid.
  • This minimum force must be determined individually for each formulation, and it depends on the amount of valsartan in the granule and on the amount and nature of the pharmaceutically acceptable excipients used.
  • WO 97/49394 proposes a range of 25 to 65 kN for the minimum compacting force in compaction.
  • the tablet prepared by the method described above has a similar high rate of disintegration as observed for capsule formulations.
  • relatively small tablets can be obtained which have a high rate of disintegration, thus giving a sufficiently high rate of release of the active ingredient from the formulation, which is essentially due to the use of a minimum compaction force.
  • a granule of active ingredient consisting exclusively of valsartan or a pharmaceutically acceptable salt thereof and optionally another active substance
  • a tablet containing this active substance or active substances preferably a film tablet, which has a high release rate for valsartan
  • the term granules the usual meaning for the skilled person and is an aggregation or aggregation of finer powder particles.
  • the present invention therefore relates to a process for the preparation of a valsartan-containing tablet, comprising the step:
  • Valsartan is soluble in ethanol and methanol and less soluble in water.
  • Valsartan is self-adhesive, so it can act as its own binder.
  • the active ingredient granules according to the invention can be prepared by wet granulation with the abovementioned solvents and mixtures thereof as granulating liquid, ie without the addition of the binders customarily used in wet granulation, or by dry granulation.
  • the active ingredient granules according to the invention are obtained by dry granulation, wherein the dry granulation comprises the steps: - A -
  • step (i) compacting a powder of valsartan or a pharmaceutically acceptable salt thereof; or compacting a powder mixture of valsartan or a pharmaceutically acceptable salt thereof and another active ingredient, and ii) granulating the concentrate of step (i).
  • the compacting is roll compaction. It has been found that for the preparation of the active ingredient granules, the compacting rollers preferably exert a compression pressure of 40 to 80 bar.
  • the method according to the invention comprises the additional steps:
  • Step (a) pharmaceutically acceptable auxiliaries, optionally another active ingredient and optionally valsartan or a pharmaceutically acceptable salt thereof as a powder, and c) compressing the mixture from step (b) to the tablet.
  • the other active ingredient is preferably a diuretic, e.g. Hydrochlorothiazide (HCT).
  • HCT Hydrochlorothiazide
  • AIs fillers may, for.
  • cellulose powder calcium diphosphate, various starches such. Corn starch, microcrystalline cellulose, silicified microcrystalline cellulose, calcium carbonate, calcium lactate, dextrose, lactose (anhydrous or as monohydrate), mannitol and the like.
  • Sodium starch glycolate, microcrystalline cellulose and low substituted sodium carboxymethyl cellulose and the like As a lubricant for improving the flow properties or the flowability, in particular highly disperse silica, z.
  • a colloidal, anhydrous silicic acid, magnesium trisilicate, cellulose powder, talc, tricalcium phosphate and the like can be used.
  • stearic acid, magnesium stearate, polyethylene glycol (PEG 4000-8000), talc and the like can be used particularly.
  • the present invention relates to a drug granules consisting solely of valsartan or a pharmaceutically acceptable salt thereof and optionally another active ingredient.
  • This active ingredient granules is an intermediate in the preparation of a valsartan-containing tablet according to the method of the invention.
  • the active ingredient granules according to the invention are prepared by:
  • step (i) compacting a powder of valsartan or a pharmaceutically acceptable salt thereof; or compacting a powder mixture of valsartan or a pharmaceutically acceptable salt thereof and another active ingredient, and ii) granulating the concentrate of step (i).
  • Release rate of valsartan from the tablet is not impaired, although the skilled person would have to assume that a compression of the active ingredient into a granulate should lead to a decrease in the release rate. That this is not the case is apparent in particular from the release profiles shown in Example 1, which were determined for tablet formulations in which different mass ratios of the active ingredient granules to the active ingredient valsartan in powder form were established.
  • the formulations Ia to Ie showed a similar release profile that was comparable to that determined for the marketed Diovan ® -Filmtablette release profile.
  • the valsart granules were obtained by roll compaction of the active ingredient powder and subsequent granulation of the resulting slugs.
  • Example 2 The film-coated tablets were prepared as indicated in Example 1. Table 2. Release profiles of the tablets of Example 2 in comparison to the Diovan ® -Filmtablette 160 mg in different dissolution media
  • the valsart granules were obtained by roll compaction of the active ingredient powder and subsequent granulation of the resulting slugs.
  • the colloidal anhydrous silica was mixed with the valsartan powder. To this mixture was then added in the order given below silicified microcrystalline cellulose, crospovidone, sodium starch glycolate and hydrochlorothiazide. After mixing, the drug granules were added. After mixing again, magnesium stearate was added and mixed again. The tableting mixture thus obtained was pressed into a tablet core. The tablet core was then film-coated.
  • the valsart granules were obtained by roll compaction of the active ingredient powder and subsequent granulation of the resulting slugs.
  • Example 5 The ingredients of the tabletting mixture except for the magnesium stearate were mixed. The resulting mixture was then treated with magnesium stearate. The tableting mixture thus obtained was mixed and pressed into a tablet core. The tablet core was then film-coated.
  • Example 5 The ingredients of the tabletting mixture except for the magnesium stearate were mixed. The resulting mixture was then treated with magnesium stearate. The tableting mixture thus obtained was mixed and pressed into a tablet core. The tablet core was then film-coated.
  • Valsartan and hydrochlorothiazide each in powder form, were mixed.
  • the active ingredient granules consisting of valsartan and hydrochlorothiazide were obtained by roll compaction of the abovementioned powder mixture and subsequent granulation of the resulting slugs.
  • the ingredients of the tabletting mixture except for the magnesium stearate were mixed.
  • the resulting mixture was then treated with magnesium stearate.
  • the tableting mixture thus obtained was mixed and pressed into a tablet core.
  • the tablet core was then film-coated.

Landscapes

  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne un procédé de fabrication d'un comprimé contenant du valsartan ainsi qu'un granulat de substance active qui est constitué exclusivement de valsartan ou d'un sel pharmaceutiquement acceptable de celui-ci et éventuellement d'une autre substance active, et son utilisation dans la fabrication du comprimé.
PCT/EP2009/007347 2008-10-17 2009-10-13 Comprimés contenant du valsartan WO2010043376A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP09736570A EP2349215A1 (fr) 2008-10-17 2009-10-13 Comprimés contenant du valsartan

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102008051783.6 2008-10-17
DE200810051783 DE102008051783A1 (de) 2008-10-17 2008-10-17 Valsartan enthaltende Tablette

Publications (1)

Publication Number Publication Date
WO2010043376A1 true WO2010043376A1 (fr) 2010-04-22

Family

ID=41511125

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2009/007347 WO2010043376A1 (fr) 2008-10-17 2009-10-13 Comprimés contenant du valsartan

Country Status (3)

Country Link
EP (1) EP2349215A1 (fr)
DE (1) DE102008051783A1 (fr)
WO (1) WO2010043376A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20230346709A1 (en) * 2017-10-13 2023-11-02 Alfred E. Tiefenbacher (Gmbh & Co. Kg) Tablet containing valsartan and sacubitril

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997049394A2 (fr) * 1996-06-27 1997-12-31 Novartis Ag Formes posologiques solides de valsartan administrees par voie orale
EP1674080A1 (fr) * 2004-12-24 2006-06-28 KRKA, D.D., Novo Mesto Composition pharmaceutique comprenant du valsartan
WO2007022113A2 (fr) * 2005-08-17 2007-02-22 Novartis Ag Formes posologiques solides de valsartan et d'amlodipine et procede de preparation afferent
US20080020042A1 (en) * 2003-10-14 2008-01-24 Peter Gruber Dosage form of sodium ibuprofen

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9415048D0 (en) * 1994-07-26 1994-09-14 Leo Pharm Prod Ltd Tablet
WO2005082329A2 (fr) * 2004-02-19 2005-09-09 Ranbaxy Laboratories Limited Procede de preparation de formes posologiques solides de valsartan et d'hydrochlorthiazide
DE502006005084D1 (de) * 2005-08-15 2009-11-26 Siegfried Generics Int Ag Filmtablette oder Granulat enthaltend ein Pyridylpyrimidin
DE102005054610B4 (de) * 2005-11-08 2010-06-10 Awd.Pharma Gmbh & Co. Kg Flupirtin enthaltende Arzneimittelzubereitung mit kontrollierter Wirkstofffreisetzung
WO2008064338A2 (fr) * 2006-11-22 2008-05-29 Rubicon Research Pvt. Ltd. Formulation de valsartan pour administration pulsatile

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997049394A2 (fr) * 1996-06-27 1997-12-31 Novartis Ag Formes posologiques solides de valsartan administrees par voie orale
US20080020042A1 (en) * 2003-10-14 2008-01-24 Peter Gruber Dosage form of sodium ibuprofen
EP1674080A1 (fr) * 2004-12-24 2006-06-28 KRKA, D.D., Novo Mesto Composition pharmaceutique comprenant du valsartan
WO2007022113A2 (fr) * 2005-08-17 2007-02-22 Novartis Ag Formes posologiques solides de valsartan et d'amlodipine et procede de preparation afferent

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20230346709A1 (en) * 2017-10-13 2023-11-02 Alfred E. Tiefenbacher (Gmbh & Co. Kg) Tablet containing valsartan and sacubitril

Also Published As

Publication number Publication date
DE102008051783A1 (de) 2010-04-22
EP2349215A1 (fr) 2011-08-03

Similar Documents

Publication Publication Date Title
DE69434479T2 (de) Tramadolhaltiges Arzneimittel mit gesteuerter Wirkstoffabgabe
DE69820287T2 (de) Pharmazeutische Zubereitung, die Chlodronat als Wirkstoff und silicifizierte mikrokristalline Cellulose als Exipienten umfasst
DE69730834T2 (de) Verfahren zur herstellung von festen oralen dosierungsformen von valsartan
DE69730314T2 (de) Dosierungsform von ibuprofen
DE69629755T2 (de) Irbesartanhaltiges Arzneimittel
DE69431247T2 (de) Oxybutyninformulierungen mit gesteuerter freisetzung
EP2477660B1 (fr) Composition pharmaceutique renfermant les agents actifs metformine et sitagliptine ou vildagliptine
DE69913197T2 (de) Natriumhydrogendivalproat-formulierungen mit gesteuerter freigabe
DE60210139T2 (de) Pharmazeutische zusammensetzungen enthaltend tegaserod
EP1762230A1 (fr) Tablette enrobé ou granulate comprenante un pyridylpyrimidine
DE69814850T2 (de) Paracetamol enthaltende schlickbare tablette
DE102004008804A1 (de) Mehrschichttablette
EP1904180A2 (fr) Forme dosifiee pharmaceutique contenant une association de principes actifs de nifedipine et/ou de nisoldipine et un antagoniste de l'angiotensine-ii
WO2012010669A2 (fr) Médicament d'administration orale contenant un mélange de silodosine et d'un copolymère basique
EP2203156A2 (fr) Candesartan cilexetil
EP2515852B1 (fr) Comprimé orodispersible contenant une base de sildenafil compactée
DE102004045037A1 (de) Pharmazeutische Darreichungsformen mit erschwerter Extrahierbarkeit eines Sympathomimetikums aus der Darreichungsform
WO2010043376A1 (fr) Comprimés contenant du valsartan
WO2019012552A4 (fr) Compositions de composés organiques ferriques
EP2303239A1 (fr) Comprimés d'aliskirène fabriqués par compression directe
DE602004009731T2 (de) Solid Darreichungsform enthaltend Koffein
DE69614694T2 (de) Therapeutische brausemischung
WO2017045743A1 (fr) Comprimés à libération des principes actifs indépendante des substances de libération
DE69909163T2 (de) Eine feste Präparation und dessen Herstellungsverfahren
KR20150096787A (ko) Ｎ-[5-[2-(3,5-디메톡시페닐)에틸]-2ｈ-피라졸-3-일]-4-[(3ｒ,5ｓ)-3,5-디메틸피페라진-1-일]벤즈아미드의 약학 제제

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09736570

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2009736570

Country of ref document: EP