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WO2012005709A2 - Composition pharmaceutique comprenant du valsartan - Google Patents

Composition pharmaceutique comprenant du valsartan Download PDF

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Publication number
WO2012005709A2
WO2012005709A2 PCT/TR2011/000168 TR2011000168W WO2012005709A2 WO 2012005709 A2 WO2012005709 A2 WO 2012005709A2 TR 2011000168 W TR2011000168 W TR 2011000168W WO 2012005709 A2 WO2012005709 A2 WO 2012005709A2
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
calcium
composition according
sodium
cellulose
Prior art date
Application number
PCT/TR2011/000168
Other languages
English (en)
Other versions
WO2012005709A3 (fr
Inventor
Mahmut Bilgic
Original Assignee
Mahmut Bilgic
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 Mahmut Bilgic filed Critical Mahmut Bilgic
Publication of WO2012005709A2 publication Critical patent/WO2012005709A2/fr
Publication of WO2012005709A3 publication Critical patent/WO2012005709A3/fr

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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
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
    • 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
    • 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
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to a pharmaceutical composition composed of granules comprising valsartan and optionally pharmaceutically acceptable excipients.
  • Valsartan (Formula I), which was disclosed in the patent numbered EP0443983 (Bl) for the first time, is named (5)-3-methyl-2-[N-( ⁇ 4-[2-(2H-l,2,3,4-tetrazol-5- yl)phenyl]phenyl ⁇ methyl)pentanamido]butanoic acid.
  • the medicaments DIOVAN and CARDOPAN are two examples of the drugs comprising the active agent valsartan used in diseases such as hypertension and coronary failure. These drugs are in film coated tablet form.
  • valsartan When valsartan contacts with air, it absorbs the water vapor in the air due to its crystalline structure. This causes the pharmaceutical composition comprising it to contain moisture. Pharmaceutical compositions with high moisture hold problems such as adhesion, staining. Furthermore, high moisture leads to degradation of the active agents and excipients and hence affects the stability of the pharmaceutical composition negatively.
  • the inventor has surprisingly found that the pharmaceutical composition prepared with granules comprising valsartan in which the moisture rate is in the range of 3% to 10% minimizes or prevents the problems specified above.
  • the present invention provides a pharmaceutical composition that is composed of granules comprising valsartan and optionally pharmaceutically acceptable excipients in which the moisture rate of said granules is adjusted in the range of 3% to 10%.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising valsartan granules which optionally contain pharmaceutically acceptable excipients and/or pharmaceutically acceptable active agents.
  • the present invention provides a process developed in order to keep the moisture rate of the granules in the range of 3% to 10%.
  • valsartan optionally one or more pharmaceutically acceptable excipients and/or optionally one or more pharmaceutically acceptable active agents are granulated with a suitable granulation solution, they are taken to the fluid bed dryer and dried at 50°C.
  • the pharmaceutical composition is ensured to be stable by reducing the moisture rate.
  • the tablet is impeded to break into pieces or a layer to break apart from the main part of the tablet during compression or coating since the moisture rate of the pharmaceutical composition is not less than 3%.
  • the granulation solution used in preparation of the granules can be selected from a group comprising solvents such as water, deionized water, toluene, benzene, acetone, methyl acetate, tetrahydrofuran, heptane, hexane, acetonitrile, alcohol (e.g. ethyl alcohol) and/or alcohol mixture though it can preferably be ethyl alcohol and/or deionized water.
  • solvents such as water, deionized water, toluene, benzene, acetone, methyl acetate, tetrahydrofuran, heptane, hexane, acetonitrile, alcohol (e.g. ethyl alcohol) and/or alcohol mixture though it can preferably be ethyl alcohol and/or deionized water.
  • alcohol e.g. ethyl alcohol
  • alcohol mixture e.g. ethyl
  • valsartan also refers to pharmaceutically acceptable derivatives of valsartan.
  • Pharmaceutically acceptable derivatives of valsartan comprise its pharmaceutically acceptable solvates, hydrates, enantiomers or diastereomers, racemates, free base, organic salts, inorganic salts, esters, polymorphs, crystalline forms and amorphous forms and/or combinations thereof.
  • the pharmaceutically acceptable excipient used in the pharmaceutical composition can be selected from a group comprising diluents, binders, disintegrants, glidant, alkalinizing agents, lubricants, coating agents and/or combinations thereof.
  • the pharmaceutical composition can further comprise other excipients such as solvents, electrolytes and coloring agents.
  • the present invention provides a medicament in which the excipients are selected from a group comprising diluents such as calcium carbonate, calcium phosphate, dibasic calcium phosphate, calcium lactate, tribasic calcium sulfate cellulose, microcrystalline cellulose, siliconized microcrystalline cellulose, cellulose powder, dextrate, dextrin, dextrose, fructose, kaolin, lactitol, lactose, maltose, mannitol, sorbitol, starch, pregelatinized starch, pregelatinized sucrose, compressible sugar and/or combinations thereof; and in which these diluents are preferably mannitol, microcrystalline cellulose and/or lactose.
  • diluents such as calcium carbonate, calcium phosphate, dibasic calcium phosphate, calcium lactate, tribasic calcium sulfate cellulose, microcrystalline cellulose, siliconized microcrystalline cellulose, cellulose powder, dextrate, dex
  • the present invention provides a medicament in which the excipients are selected from a group comprising binders such as starch, pregelatinized starch, pregelatinized syrup, alginic acid, carboxymethyl cellulose, sodium cellulose, microcrystalline dextrin ethyl cellulose gelatin glucose, microcrystalline cellulose, hydroxyethyl cellulose, hydroxyproyl cellulose, low-substituted hydroxypropyl cellulose, polyvinylpyrrolidone, crospovidone, polymethacrylate and/or combinations thereof; and in which these binders are preferably crospovidone, starch, pregelatinized starch and/or microcrystalline cellulose.
  • binders such as starch, pregelatinized starch, pregelatinized syrup, alginic acid, carboxymethyl cellulose, sodium cellulose, microcrystalline dextrin ethyl cellulose gelatin glucose, microcrystalline cellulose, hydroxyethyl cellulose, hydroxyproyl cellulose, low-sub
  • the present invention provides a medicament in which the excipients are selected from a group comprising disintegrants such as alginic acid cellulose, microcrystalline croscarmellose sodium, carboxymethyl cellulose sodium, crospovidone, polacrylline potassium, sodium starch glicolate, starch, pregelatinized starch and/or combinations thereof; and in which these disintegrants are preferably crospovidone and/or microcrystalline cellulose.
  • disintegrants such as alginic acid cellulose, microcrystalline croscarmellose sodium, carboxymethyl cellulose sodium, crospovidone, polacrylline potassium, sodium starch glicolate, starch, pregelatinized starch and/or combinations thereof.
  • the present invention provides a medicament comprising valsartan and/or pharmaceutically acceptable derivatives thereof and excipients in which the excipients are selected from a group comprising glidants such as calcium silicate, magnesium silicate, magnesium trisilicate, tribasic calcium phosphate, metallic stearates, metallic lauryl sulfates, silicone dioxide, colloidal talc, colloidal silicone dioxide, microcrystalline cellulose and/or combinations thereof; and in which these glidants are preferably silicone dioxide.
  • glidants such as calcium silicate, magnesium silicate, magnesium trisilicate, tribasic calcium phosphate, metallic stearates, metallic lauryl sulfates, silicone dioxide, colloidal talc, colloidal silicone dioxide, microcrystalline cellulose and/or combinations thereof; and in which these glidants are preferably silicone dioxide.
  • the present invention provides a medicament in which the excipients are selected from a group comprising alkalinizing agents such as alkali metal salts such as sodium carbonate, sodium hydroxide, sodium silicate, disodium hydrogen orthophosphate, sodium aluminate; alkaline earth metal salts such as calcium carbonate, calcium hydroxide, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, calcium acetate, calcium gluconate, calcium glycerophosphate, magnesium carbonate, magnesium hydroxide, magnesium sulphate, magnesium acetate, magnesium silicate, magnesium aluminate; and organic compounds such as primary, secondary and tertiary amines, cyclic amines, ⁇ , ⁇ '- dibenzylethylenediamine, diethanolamine, ethylenediamine, meglumine, monosodium glutamate, polacryline sodium, sodium alginate and/or combinations thereof; and in which these alkalinizing agents are preferably sodium hydrogen carbonate.
  • the present invention provides a medicament in which the excipients are selected from a group comprising lubricants such as calcium stearate, glyceryl behenate, magnesium stearate, calcium stearate, mineral oil, polyethylene glycol, sodium stearyl fumarate, stearic acid, talc, vegetable oil, fatty acid esters, paraffins, leucine, hydrogenated vegetable oils, metallic lauryl sulfate, sodium chloride sodium benzoate, sodium acetate and/or combinations thereof; and in which the lubricant is preferably magnesium stearate.
  • lubricants such as calcium stearate, glyceryl behenate, magnesium stearate, calcium stearate, mineral oil, polyethylene glycol, sodium stearyl fumarate, stearic acid, talc, vegetable oil, fatty acid esters, paraffins, leucine, hydrogenated vegetable oils, metallic lauryl sulfate, sodium chloride sodium benzoate, sodium a
  • the present invention provides a medicament in which the excipients are selected from a group comprising coating agents such as carboxymethyl cellulose, sodium cellulose acetate phthalate, ethylcellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose phthalate, methacrylic acid copolymer, methylcellulose polyethylene glycol, polyvinyl acetate, titanium dioxide, wax, carnauba wax and/or combinations thereof; and in which these coating agents are preferably hydroxyl propyl methyl cellulose, titanium dioxide and/or polyethylene glycol.
  • coating agents such as carboxymethyl cellulose, sodium cellulose acetate phthalate, ethylcellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose phthalate, methacrylic acid copolymer, methylcellulose polyethylene glycol, polyvinyl acetate, titanium dioxide, wax, carnauba wax and/or combinations thereof;
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a. valsartan in the range of 10% to 34% by weight and preferably in the range of 25% to 34% by weight;
  • disintegrant in the range of 1% to 15% by weight and preferably in the range of 1% to 10% by weight;
  • glidant in the range of 0% to 10% by weight and preferably in the range 0,1% to 5% by weight;
  • alkalinizing agent in the range of 0% to 15% by weight and preferably in the range of ⁇ % to 10% by weight;
  • lubricant in the range of 0% to 10% by weight and preferably in the range of 0,1% to 5% by weight.
  • the pharmaceutical composition in another aspect, can be in coated or uncoated tablet, orally disintegrated tablet, capsule, pellet, powder, granule or mini tablet form and preferably in coated tablet form.
  • the pharmaceutical composition can be prepared by conventional methods after the granulation and drying operations of the present invention are applied.
  • the pharmaceutical composition can additionally comprise one or more excipients selected from a group comprising rennin inhibitor, angiotensin converting enzyme inhibitor, calcium channel blocker, aldosterone synthesis inhibitor, aldosterone antagonist, endothelin antagonist and diuretic.
  • excipients selected from a group comprising rennin inhibitor, angiotensin converting enzyme inhibitor, calcium channel blocker, aldosterone synthesis inhibitor, aldosterone antagonist, endothelin antagonist and diuretic.
  • the pharmaceutical composition can additionally comprise one or more active agents selected from a group comprising aliskiren, remikiren, captopril, zofenopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, fosinopril, alacepril, cilazapril, delapril, imidapril, moexipril, rentiapril, spinapril, temocapril, trandolapril; dihydropyridines such as amlodipine, nifedipine, nilvadipine, nicardipine; verapamil, gallopamil, diltiazem, fendiline, mibefradil, bepridil, fluspirilene, spironolactone, eplerenone, canrenone, prorenone, mexrenone,
  • the present invention relates to use of the pharmaceutical composition in the treatment or prophylaxis of, as preferably hypertension, congestive heart failure, angina, myocardial infarction, embolism, diabetic nephropathy, diabetic cardiomyopathy, renal failure, peripheral vascular diseases, left ventricular hypertrophy, cognitive dysfunction, Alzheimer disease, paralysis, headache and chronic heart disease.
  • a granulation solution is prepared by mixing a suitable amount of ethyl alcohol and deionized water.
  • the active agent valsartan of 80 mg is mixed with the granulation solution prepared and it is granulated.
  • the granules are taken to the fluid bed dryer. They are dried at 50°C there and valsartan granules with 3,5% moisture content are obtained.

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

Abstract

L'invention concerne une composition pharmaceutique composée de granules comprenant du valsartan et, éventuellement, des excipients pharmaceutiquement acceptables.
PCT/TR2011/000168 2010-07-05 2011-07-04 Composition pharmaceutique comprenant du valsartan WO2012005709A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2010/05419A TR201005419A2 (tr) 2010-07-05 2010-07-05 Valsartan içeren farmasötik bileşim.
TR2010/05419 2010-07-05

Publications (2)

Publication Number Publication Date
WO2012005709A2 true WO2012005709A2 (fr) 2012-01-12
WO2012005709A3 WO2012005709A3 (fr) 2012-07-12

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Application Number Title Priority Date Filing Date
PCT/TR2011/000168 WO2012005709A2 (fr) 2010-07-05 2011-07-04 Composition pharmaceutique comprenant du valsartan

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TR (1) TR201005419A2 (fr)
WO (1) WO2012005709A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3342400A1 (fr) * 2016-12-31 2018-07-04 Abdi Ibrahim Ilac Sanayi ve Ticaret A.S. Composition pharmaceutique comprenant de la valsartane et du chlorthalidone

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0443983B1 (fr) 1990-02-19 1996-02-28 Ciba-Geigy Ag Composés acylés
WO2009022169A1 (fr) 2007-08-10 2009-02-19 Generics [Uk] Limited Composition de valsartan solide

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TR200703568A1 (tr) * 2007-05-24 2008-07-21 Sanovel �La� Sanay� Ve T�Caret Anon�M ��Rket� Valsartan formülasyonları
CN101744813A (zh) * 2010-01-21 2010-06-23 扬子江药业集团有限公司 复方氨氯地平缬沙坦固体制剂及其制备方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0443983B1 (fr) 1990-02-19 1996-02-28 Ciba-Geigy Ag Composés acylés
WO2009022169A1 (fr) 2007-08-10 2009-02-19 Generics [Uk] Limited Composition de valsartan solide

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3342400A1 (fr) * 2016-12-31 2018-07-04 Abdi Ibrahim Ilac Sanayi ve Ticaret A.S. Composition pharmaceutique comprenant de la valsartane et du chlorthalidone

Also Published As

Publication number Publication date
WO2012005709A3 (fr) 2012-07-12
TR201005419A2 (tr) 2012-01-23

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