WO2006134604A1 - Composition combinant un inhibiteur d’absorption du cholestérol et un inhibiteur de la 3-hydroxy-3-méthylglutaryl-coenzyme a (hmg-coa) réductase - Google Patents

Composition combinant un inhibiteur d’absorption du cholestérol et un inhibiteur de la 3-hydroxy-3-méthylglutaryl-coenzyme a (hmg-coa) réductase Download PDF

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Publication number
WO2006134604A1
WO2006134604A1 PCT/IN2005/000196 IN2005000196W WO2006134604A1 WO 2006134604 A1 WO2006134604 A1 WO 2006134604A1 IN 2005000196 W IN2005000196 W IN 2005000196W WO 2006134604 A1 WO2006134604 A1 WO 2006134604A1
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Prior art keywords
weight
range
formulation
ezetimibe
tablet
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Ceased
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PCT/IN2005/000196
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English (en)
Inventor
Male Srinivas Reddy
Pothireddy Venkateswar Reddy
Muppidi Vanaja
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Hetero Drugs Ltd
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Hetero Drugs Ltd
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    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • 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
    • A61K31/66—Phosphorus compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics

Definitions

  • the present invention relates to stable pharmaceutical compositions of antihyperlipoproteinemic drugs.
  • Ezetimibe chemically, (3R,4S)-1-(4-fluorophenyl)-3-[3(S)-3-(4- fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)-2-azetidinone.
  • Ezetimibe is a cholesterol absorption inhibitor.
  • the therapeutic uses of ezetimibe and related compounds, and their preparations were disclosed in U.S. patent No.
  • Ezetimibe is commercially available as 10 mg tablets. It is sold under the name ZETIA.
  • Simvastatin chemically, 2,2-dimethylbutarioic acid (1S,3R,7S,8S,8aR)- 1 ,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-[(2R,4R)-(tetrahydro-4-hydroxy-6- oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl ester.
  • Simvastatin is a 3-hydroxy-3- methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor.
  • HMG-CoA 3-hydroxy-3- methylglutaryl-coenzyme A
  • Simvastatin is commercially available as 5 mg, 10 mg, 20 mg, 40 mg and 80 mg tablets. It is sold under the name ZOCOR.
  • Atorvastatin chemically, ( ⁇ R, ⁇ R)-2-(4-fluorophenyl)- ⁇ , ⁇ -dihydroxy-5- (1 -methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1 H-pyrrole-1 -heptanoic acid.
  • Atorvastatin is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor.
  • HMG-CoA 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor.
  • the therapeutic uses of atorvastatin and related compounds, and their preparations were disclosed in U.S. patent No. 5,273,995.
  • Atorvastatin is commercially available as 10 mg, 20 mg, 40 mg and 80 mg tablets. It is sold under the name LIPITOR.
  • Rosuvastatin chemically, [3R-[3R * ,5S*(E)]]-7-[4-(4-fluorophenyl)-6-(1- methylethyl)-2-[methyl(methylsulfonyl)amino]-5-pyrimidinyl]-3,5-dihydroxy-6- heptenoic acid.
  • Rosuvastatin is a HMG-CoA reductase inhibitor. The therapeutic uses of rosuvastatin and related compounds, and their preparations were disclosed in U.S. patent No. 5,260,440.
  • Rosuvastatin is commercially available as 5 mg, 10 mg, 20 mg and 40 mg tablets. It is sold under the name CRESTOR.
  • the object of the present invention is to provide stable solid oral pharmaceutical compositions of antihyperlipoproteinemic drugs.
  • the present invention relates to a stable antihyperlipoproteinemic combination of solid oral pharmaceutical compositions comprising ezetimibe, HMG-CoA reductase inhibitor, disintegrants and glidants.
  • a stable antihyperlipoproteinemic combination of solid oral pharmaceutical formulations which comprises ezetimibe, an HMG-CoA reductase inhibitor, disintegrants selected from starch, croscarmellose sodium and crospovidone, glidants selected from colloidal anhydrous silica and magnesium stearate.
  • Other additives conventionally used for pharmaceutical formulations may be included in the present formulation.
  • the preferable HMG-CoA reductase inhibitors are simvastatin, atorvastatin and rosuvastatin; or a salt thereof.
  • the particularly preferable stable antihyperlipoproteinemic combination of solid oral pharmaceutical formulations which comprises ezetimibe in the range of 1 to 15% by weight, more preferably 1.5 to 11% by weight; the HMG- CoA reductase inhibitor selected from simvastatin in the range of 1 to 25% by weight, more preferably 2 to 20% by weight; atorvastatin or a salt thereof in the range of 1 to 30% by weight, more preferably 2 to 25% by weight equivalent to atorvastatin and rosuvastatin or a salt thereof in the range of 2 to 12% by weight, more preferably 4 to 10% by weight equivalent to rosuvastatin; starch in the range of 2 to 25% by weight, more preferably 3 to 20% by weight; croscarmellose sodium in the range of 1 to 8% by weight, more preferably 1.5 to 6.5% by weight; crospovidone in the range of 1 to 8% by weight, more preferably 1.5 to 6.5% by weight; colloidal anhydrous silica in the range of 0.1 to 2.5% by weight
  • a stable antihyperlipoproteinemic combination of solid oral pharmaceutical formulations according to the invention comprises additives, which are conventionally used in dosage forms. These include but are not limited to disintegrants, binders, lubricants, glidants, fillers or diluents, stabilizing agents and the like.
  • disintegrants one can particularly mention sodium starch glycolate, starch, croscarmellose sodium, crospovidone, carboxymethylcellulose calcium, carboxymethylcellulose sodium, magnesium aluminum silicate or a mixture thereof.
  • binders one can particularly mention starch, hydroxypropylcellulose, polyvinylpyrolidone k-30, hydroxypropylcellulose (low- substituted); or a mixture thereof.
  • stearic acid pharmaceutically acceptable derivatives of stearic acid, talc, sodium stearyl fumarate, glyceryl behenate, magnesium silicate, magnesium trisilicate, hydrogenated castor oil; or a mixture thereof.
  • colloidal anhydrous silica talc or a mixture thereof.
  • preservatives one can particularly mention butylated hydroxy anisole, butylated hydroxy toluene, methyl paraben, propyl paraben; or a mixture thereof.
  • fillers one can particularly mention calcium carbonate, dibasic calcium phosphate, lactose, magnesium carbonate, sucrose, starch, magnesium oxide, lactose anhydrous, microcrystalline cellulose, mannitol; or a mixture thereof.
  • Other ingredients such as coating materials, anti-adherents, plasticizer, colorants, opacifiers, antioxidants and solvents conventionally used for pharmaceutical formulations.
  • the pharmaceutical composition may be for example, in the form of a tablet, a caplet, pellets, a capsule, granules, a pill, powder or a sachet.
  • the pharmaceutical composition is in the form of a combination antihyperlipoproteinemic tablet.
  • Stable mixture which is highly compressible, have good flow properties, thereby providing the tablets with excellent physical properties.
  • the pharmaceutical composition of the present invention is administered orally.
  • An improved stable antihyperlipoproteinemic combination of solid oral pharmaceutical formulations which comprises ezetimibe, simvastatin, starlac, ethanol, butylated hydroxy anisole, magnesium stearate, crospovidone, croscarmellose sodium, hydroxypropylcellulose (low-substituted), purified talc, lake brilliant blue, colloidal anhydrous silica, hydroxypropylmethylcellulose- 15cps, titanium dioxide and triacetin.
  • the present invention provides a formulation suitable for forming ezetimibe and simvastatin combination tablets comprising ezetimibe in the range of 1 to 10% by weight, more preferably 1.5 to 7.5% by weight, simvastatin in the range of 2 to 23% by weight, more preferably 3 to 18% by weight, starlac in the range of 41 to 97% by weight, more preferably 61 to 87% by weight, butylated hydroxy anisole in the range of 0.01 to 0.004% by weight, more preferably 0.01 to 0.03% by weight, magnesium stearate in the range of 1 to 3% by weight, more preferably 1.5 to 2.5% by weight, crospovidone in the range of 1 to 6% by weight, more preferably 1.5 to 5% by weight, croscarmellose sodium in the range of 1 to 4% by weight, more preferably 1.5 to 3% by weight, hydroxypropylcellulose (low-substituted) in the range of 2 to 7% by weight, more preferably 2.5 to 6.5% by weight, colloidal anhydr
  • solid dosage forms contain a number of additional additives used in single dosage units.
  • the particularly preferable tablet formulations are: i) Ezetimibe (10mg) and simvastatin (5mg); which comprises ezetimibe is 6.7% by weight, simvastatin is 3.3% by weight, starlac is 77.3% by weight, butylated hydroxy anisole is 0.02% by weight, magnesium stearate is 1.7% by weight, crospovidone is 2.7% by weight, croscarmellose sodium is 2% by weight, hydroxypropylcellulose (low-substituted) is 5.3% by weight, colloidal anhydrous silica is 1% by weight, based on the total weight of the tablet, hydroxypropylmethylcellulose-i ⁇ cps is 63.7% by weight, purified talc is 8% by weight, lake brilliant blue is 10% by weight, titanium dioxide is 12.7% by weight and triacetin is 5.7% by weight, based
  • Ezetimibe (10mg) and simvastatin (40mg); which comprises ezetimibe is 2.6% by weight, simvastatin is 10.3% by weight, starlac is 75.1% by weight, butylated hydroxy anisole is 0.02% by weight, magnesium stearate is 2.1% by weight, crospovidone is 2.1% by weight, croscarmellose sodium is 1.8% by weight, hydroxypropylcellulose (low-substituted) is 5.1% by weight, colloidal anhydrous silica is 1 % by weight, based on the total weight of the tablet, hydroxypropylmethylcellulose-15cps is 63.2% by weight, purified talc is 8.2% by weight, lake brilliant blue is 10% by weight, titanium dioxide is 12.8% by weight and triacetin is 2.3% by weight, based on the total weight of the coating material.
  • Ezetimibe (10mg) and simvastatin (80mg); which comprises ezetimibe is 2% by weight, simvastatin is 16% by weight, starlac is 67.8% by weight, butylated hydroxy anisole is 0.02% by weight, magnesium stearate is 2% by weight, crospovidone is 4% by weight, croscarmellose sodium is 2.6% by weight, hydroxypropylcellulose (low-substituted) is 4.6% by weight, colloidal anhydrous silica is 1% by weight, based on the total weight of the tablet, hydroxypropylmethylcellulose ' ⁇ 15cps is 63.3% by weight, purified talc is 8.1% by weight, lake brilliant blue is 10% by weight, titanium dioxide is 12.8% by weight and triacetin is 5.8% by weight, based on the total weight of the coating material.
  • An improved stable antihyperlipoproteinemic combination of solid oral pharmaceutical formulations which comprises ezetimibe, atorvastatin and rosuvastatin or a salt thereof, light calcium carbonate, lactose, starch, croscarmellose sodium, polyvinylpyrrolidone k-30, isopropyl alcohol, titanium dioxide, magnesium stearate, colloidal anhydrous silica, crospovidone, hydroxypropylmethylcellulose-15cps, purified talc, lake sunset yellow and triacetin.
  • the present invention provides a formulation suitable for forming ezetimibe and atorvastatin; or a salt thereof combination tablets comprising ezetimibe in the range of 1.5 to 13% by weight, more preferably 2 to 10% by weight, atorvastatin; or a salt thereof in the range of 3 to 31% by weight, more preferably 4 to 24% by weight equivalent to atorvastatin, light calcium carbonate in the range of 2 to 8% by weight, more preferably 3 to 6.5% by weight, lactose in the range of 27 to 80% by weight, more preferably 40 to 63% by weight, starch in the range of 5 to 24% by weight, more preferably 8 to 19% by weight, croscarmellose sodium in the range of 2 to 8% by weight, more preferably 3 to 6% by weight, polyvinylpyrrolidone k-30 in the range of 1 to 7% by weight, more preferably 2.5 to 6% by weight, magnesium stearate in the range of 1 to 4% by weight, more preferably 1.5 to 3% by
  • solid dosage forms contain a number of additional additives used in single dosage units.
  • the particularly preferable tablet formulations are: i) Ezetimibe (10mg) and atorvastatin (5mg); which comprises ezetimibe is 9.09% by weight, atorvastatin or a salt thereof is 4.92% by weight equivalent to atorvastatin, light calcium carbonate is 3.64% by weight, lactose is 51.4% by weight, starch is 17.3% by weight, croscarmellose sodium is 3.62% by weight, polyvinylpyrolidone k-30 is 4.09% by weight, magnesium stearate is 1.82% by weight, colloidal anhydrous silica is 1.36% by weight, crospovidone is 2.73% by weight, based on the total weight of the tablet, hydroxypropylmethylcellulose-15cps is 72.3% by weight, purified talc is 7.73% by weight, lake sunset yellow is 1.36% by weight,
  • the present invention provides a formulation suitable for forming ezetimibe and rosuvastatin or a salt thereof combination tablets comprising ezetimibe in the range of 2 to 13% by weight, more preferably 3 to 10% by weight, rosuvastatin; or a salt thereof in the range of 2 to 10.5% by weight, more preferably 4 to 8.5% by weight equivalent to rosuvastatin, light calcium carbonate in the range of 1 to 4% by weight, more preferably 1.5 to 3% by weight, lactose in the range of 32 to 83% by weight, more preferably 49 to 65% by weight, starch in the range of 8 to 21% by weight, more preferably 12 to 16.5% by weight, croscarmellose sodium in the range of 2 to 6.5% by weight, more preferably 2.5 to 5% by weight, polyvinylpyrrolidone k-30 in the range of 1 to 5% by weight, more preferably 2 to 3.5% by weight, magnesium stearate in the range of 1 to 3.5% by weight, more preferably 1.5 to
  • solid dosage forms contain a number of additional additives used in single dosage units.
  • the particularly preferable tablet formulations are: i) Ezetimibe (10mg) and rosuvastatin (5mg); which comprises ezetimibe is 9.09% by weight, rosuvastatin or a salt thereof is 4.74% by weight equivalent to rosuvastatin, light calcium carbonate is 2.3% by weight, lactose is 54.5% by weight, starch is 13.9% by weight, croscarmellose sodium is 4.6% by weight, polyvinylpyrolidone k-30 is 3.2% by weight, magnesium stearate is 1.8% by weight, colloidal anhydrous silica is 0.9% by weight, crospovidone is 5% by weight, based on the total weight of the tablet, hydroxypropylmethylcellulose- 15cps is 71.8% by weight, purified talc is 8.2% by weight, lake sunset yellow is 1.4% by weight, titanium dioxide is
  • rosuvastatin or a salt thereof is 5.95% by weight equivalent to rosuvastatin
  • light calcium carbonate is 2.3% by weight
  • lactose is 57.5% by weight
  • starch is 13.7% by weight
  • croscarmellose sodium is 4% by weight
  • ⁇ polyvinylpyrolidone k-30 is 2.9% by weight, magnesium stearate is 2.3% by weight, colloidal anhydrous silica is 1.1% by weight, crospovidone is 4.6% by weight, based on the total weight of the tablet, hydroxypropylmethylcellulose- 15cps is 72.3% by weight, purified talc is 8% by weight, lake sunset yellow is 1.43% by weight, titanium dioxide is 12.6% by weight and triacetin is 5.7% by weight, based on the total weight of the coating material.
  • the ezetimibe, simvastatin and starlac are granulated using binder solution of butylated hydroxy anisole and ethanol in planetary mixer, rapid mixer granulator; or other suitable granulator. This wet mass may be then dried. The dried granulation may be then milled to acheive the desired particle size distribution and then blended with the other ingredients. This blend is compressed into tablets. These compressed tablets are coated using a non aqueous solution of hydroxypropylmethylcellulose-15cps, purified talc, lake brilliant blue, titanium dioxide and triacetin by using autocota, neocota; or other suitable coating pan.
  • Example 1 Example 1
  • Example 2 The components and their amounts were as follows: Ezetimibe (10mg) and simvastatin (10mg) tablets:
  • Ezetimibe (10mg) and simvastatin (40mg) tablets were as follows: Ezetimibe (10mg) and simvastatin (40mg) tablets:
  • the ezetimibe, HMG-CoA reductase inhibitor, light calcium carbonate, lactose, starch and croscarmellose sodium are granulated using binder solution of polyvinylpyrrolidone k-30 and isopropyl alcohol in planetary mixer, rapid mixer granulator; or other suitable granulator. This wet mass may be then dried. The dried granulation may be then milled to acheive the desired particle size distribution and then blended with the other ingredients. This blend is compressed into tablets.
  • These compressed tablets are coated using a non aqueous solution of hydroxypropylmethylcellulose- 15cps, purified talc, lake sunset yellow, titanium dioxide and triacetin by using autocota, neocota; or other suitable coating pan.
  • Ezetimibe (10mg) and atorvastatin (5mg) tablets Ingredients Quantity (mg) %(W ⁇ /V)
  • Example 12 The components and their amounts were as follows: Ezetimibe (10mg) and rosuvastatin (10mg) tablets: Ingredients Quantity (mg) %(W ⁇ /V)
  • Example 13 The components and their amounts were as follows: Ezetimibe (10mg) and rosuvastatin (20mg) tablets:

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Abstract

La présente invention concerne une combinaison antihyperlipoprotéinémique stable de compositions pharmaceutiques orales solides d’ézétimibe, d’inhibiteur de HMG-CoA réductase, de désintégrants et d’agents de glissement. Par exemple, ladite combinaison comprend de l’ézétimibe, de la simvastatine, du starlac, de l’éthanol, de l'hydroxyanisole butylé, du stéarate de magnésium, de la crospovidone, de la croscarmellose sodique, de l’hydroxypropylcellulose (faiblement substituée), du talc purifié, du bleu brillant FCF, de la silice colloïdale anhydre, de l’hydroxypropylméthylcellulose de 15 cps, du dioxyde de titane et de la triacétine.
PCT/IN2005/000196 2005-06-15 2005-06-15 Composition combinant un inhibiteur d’absorption du cholestérol et un inhibiteur de la 3-hydroxy-3-méthylglutaryl-coenzyme a (hmg-coa) réductase Ceased WO2006134604A1 (fr)

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PCT/IN2005/000196 WO2006134604A1 (fr) 2005-06-15 2005-06-15 Composition combinant un inhibiteur d’absorption du cholestérol et un inhibiteur de la 3-hydroxy-3-méthylglutaryl-coenzyme a (hmg-coa) réductase

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Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007103453A1 (fr) * 2006-03-06 2007-09-13 Teva Pharmaceutical Industries Ltd. Compositions à base d'ézétimibe
WO2008101723A3 (fr) * 2007-02-23 2008-11-27 Krka Composition pharmaceutique comprenant un inhibiteur d'absorption du cholestérol
US7470678B2 (en) 2002-07-05 2008-12-30 Astrazeneca Ab Diphenylazetidinone derivatives for treating disorders of the lipid metabolism
WO2009024889A2 (fr) 2007-08-21 2009-02-26 Ranbaxy Laboratories Limited Composition pharmaceutique comprenant un inhibiteur de réductase hmg-coa et un ézétimibe
WO2009016358A3 (fr) * 2007-07-27 2009-07-23 Cipla Ltd Compositions pharmaceutiques et leur procédé de préparation
WO2009156796A1 (fr) * 2008-06-27 2009-12-30 Abdi Ibrahim Ilac Sanayi Ve Ticaret Anonim Sirketi Compositions pharmaceutiques de rosuvastatine calcium
WO2010021609A1 (fr) * 2008-08-22 2010-02-25 Mahmut Bilgic Préparation pharmaceutique améliorant la solubilité et la stabilité
WO2010021608A1 (fr) * 2008-08-22 2010-02-25 Mahmut Bilgic Préparation pharmaceutique améliorant la solubilité
EP2168573A1 (fr) * 2008-09-30 2010-03-31 LEK Pharmaceuticals D.D. Formulations contentant d'ézétimibe
WO2010053343A1 (fr) * 2008-11-10 2010-05-14 Psicofarma S.A. De C.V. Procédé d'obtention d'une composition de rosuvastatine calcique et produit obtenu
EP2204170A1 (fr) * 2008-12-01 2010-07-07 LEK Pharmaceuticals D.D. Composition pharmaceutique comprenant ézétimide et simvastatine
EP2216016A1 (fr) 2009-02-06 2010-08-11 LEK Pharmaceuticals d.d. Procédé pour la préparation d'une composition pharmaceutique comprenant de l'ézétimibe
US7842684B2 (en) 2006-04-27 2010-11-30 Astrazeneca Ab Diphenylazetidinone derivatives possessing cholesterol absorption inhibitor activity
US7863265B2 (en) 2005-06-20 2011-01-04 Astrazeneca Ab 2-azetidinone derivatives and their use as cholesterol absorption inhibitors for the treatment of hyperlipidaemia
WO2011002422A2 (fr) 2009-07-02 2011-01-06 Bilgic Mahmut Formulation pharmaceutique améliorant la solubilité
US7871998B2 (en) 2003-12-23 2011-01-18 Astrazeneca Ab Diphenylazetidinone derivatives possessing cholesterol absorption inhibitory activity
WO2011019326A2 (fr) 2009-07-02 2011-02-17 Mahmut Bilgic Formulation pharmaceutique permettant d'augmenter la solubilité et la stabilité
US7893048B2 (en) 2005-06-22 2011-02-22 Astrazeneca Ab 2-azetidinone derivatives as cholesterol absorption inhibitors for the treatment of hyperlipidaemic conditions
US7906502B2 (en) 2005-06-22 2011-03-15 Astrazeneca Ab 2-azetidinone derivatives as cholesterol absorption inhibitors for the treatment of hyperlipidaemic conditions
WO2011002424A3 (fr) * 2009-07-02 2011-04-28 Bilgic Mahmut Préparation pharmaceutique améliorant la solubilité et la stabilité
EP2368543A1 (fr) 2010-03-25 2011-09-28 KRKA, tovarna zdravil, d.d., Novo mesto Procédé de préparation de composition pharmaceutique granulée comprenant de la simvastatine et/ou ézétimibe
WO2012064306A3 (fr) * 2010-11-11 2012-08-09 Bilgic Mahmut Formulations effervescentes de rosuvastatine
US20130237579A1 (en) * 2007-07-13 2013-09-12 Timothy Stanley Stable pharmaceutical compositions comprising one or more hmg-coa reductas inhibitiors
EP2805714A1 (fr) * 2013-04-25 2014-11-26 Antibiotice S.A. Composition pharmaceutique stable comprenant de la rosuvastatine calcique amorphe
WO2014195900A3 (fr) * 2013-06-05 2015-02-05 Alparis S.A. De C.V. Compositions pharmaceutiques à administration par voie orale destinées à être utilisées dans les dyslipidémies
WO2015044698A3 (fr) * 2013-09-30 2015-05-14 Egis Gyógyszergyár Zrt. Composition médicale contenant un inhibiteur de l'absorption du cholestérol et un inhibiteur de la biosynthèse du cholestérol
WO2015093859A1 (fr) * 2013-12-18 2015-06-25 (주) 드림파마 Préparation pharmaceutique combinée contenant un inhibiteur de hmg-coa réductase et un inhibiteur de l'absorption du cholestérol
CN105287513A (zh) * 2015-10-23 2016-02-03 浙江永宁药业股份有限公司 一种依折麦布药物组合物及其制备方法
WO2021019499A1 (fr) 2019-07-31 2021-02-04 TECNIMEDE - Sociedade Técnico-medicinal, SA Compositions solides orales à libération immédiate à unités multiples, procédés et utilisations de celles-ci

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US7893048B2 (en) 2005-06-22 2011-02-22 Astrazeneca Ab 2-azetidinone derivatives as cholesterol absorption inhibitors for the treatment of hyperlipidaemic conditions
US7906502B2 (en) 2005-06-22 2011-03-15 Astrazeneca Ab 2-azetidinone derivatives as cholesterol absorption inhibitors for the treatment of hyperlipidaemic conditions
EP1849459A1 (fr) * 2006-03-06 2007-10-31 Teva Pharmaceutical Industries Ltd. Compositions d'ézétimibe
WO2007103453A1 (fr) * 2006-03-06 2007-09-13 Teva Pharmaceutical Industries Ltd. Compositions à base d'ézétimibe
US7842684B2 (en) 2006-04-27 2010-11-30 Astrazeneca Ab Diphenylazetidinone derivatives possessing cholesterol absorption inhibitor activity
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WO2009024889A2 (fr) 2007-08-21 2009-02-26 Ranbaxy Laboratories Limited Composition pharmaceutique comprenant un inhibiteur de réductase hmg-coa et un ézétimibe
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JP2011525901A (ja) * 2008-06-27 2011-09-29 アブディ イブラヒム イラク サナイ ベ ティカレット アノニム シルケティ ロスバスタチンカルシウム含有医薬組成物
WO2009156796A1 (fr) * 2008-06-27 2009-12-30 Abdi Ibrahim Ilac Sanayi Ve Ticaret Anonim Sirketi Compositions pharmaceutiques de rosuvastatine calcium
WO2010021608A1 (fr) * 2008-08-22 2010-02-25 Mahmut Bilgic Préparation pharmaceutique améliorant la solubilité
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WO2010037728A2 (fr) 2008-09-30 2010-04-08 Lek Pharmaceuticals D.D. Nouvelles formules d'ézétimibe
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WO2010037728A3 (fr) * 2008-09-30 2010-06-10 Lek Pharmaceuticals D.D. Nouvelles formules d'ézétimibe
WO2010053343A1 (fr) * 2008-11-10 2010-05-14 Psicofarma S.A. De C.V. Procédé d'obtention d'une composition de rosuvastatine calcique et produit obtenu
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WO2010063667A3 (fr) * 2008-12-01 2010-08-05 Lek Pharmaceuticals D.D. Composition pharmaceutique contenant de l’ézétimibe et de la simvastatine
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EP2216016A1 (fr) 2009-02-06 2010-08-11 LEK Pharmaceuticals d.d. Procédé pour la préparation d'une composition pharmaceutique comprenant de l'ézétimibe
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WO2011002422A3 (fr) * 2009-07-02 2011-04-28 Bilgic Mahmut Formulation pharmaceutique améliorant la solubilité
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WO2011116973A1 (fr) 2010-03-25 2011-09-29 Krka, Tovarna Zdravil, D.D., Novo Mesto Procédé de préparation d'une composition pharmaceutique sous forme de granulés contenant de la simvastatine et/ou de l'ézétimib
WO2012064306A3 (fr) * 2010-11-11 2012-08-09 Bilgic Mahmut Formulations effervescentes de rosuvastatine
EP2805714A1 (fr) * 2013-04-25 2014-11-26 Antibiotice S.A. Composition pharmaceutique stable comprenant de la rosuvastatine calcique amorphe
WO2014195900A3 (fr) * 2013-06-05 2015-02-05 Alparis S.A. De C.V. Compositions pharmaceutiques à administration par voie orale destinées à être utilisées dans les dyslipidémies
WO2015044698A3 (fr) * 2013-09-30 2015-05-14 Egis Gyógyszergyár Zrt. Composition médicale contenant un inhibiteur de l'absorption du cholestérol et un inhibiteur de la biosynthèse du cholestérol
EA034711B1 (ru) * 2013-09-30 2020-03-12 Эгиш Дьёдьсердьяр Зрт. Лекарственная композиция, содержащая ингибитор всасывания холестерина и ингибитор биосинтеза холестерина
WO2015093859A1 (fr) * 2013-12-18 2015-06-25 (주) 드림파마 Préparation pharmaceutique combinée contenant un inhibiteur de hmg-coa réductase et un inhibiteur de l'absorption du cholestérol
EP3085364A4 (fr) * 2013-12-18 2017-08-23 Alvogen Korea Co., Ltd. Préparation pharmaceutique combinée contenant un inhibiteur de hmg-coa réductase et un inhibiteur de l'absorption du cholestérol
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CN113069456A (zh) * 2013-12-18 2021-07-06 艾威群韩国株式会社 含有HMG-CoA还原酶抑制剂和胆固醇吸收抑制剂的药物组合制剂
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