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WO2010140992A1 - Compositions pharmaceutiques stables contenant du calcium rosuvastatine - Google Patents

Compositions pharmaceutiques stables contenant du calcium rosuvastatine Download PDF

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Publication number
WO2010140992A1
WO2010140992A1 PCT/TR2010/000103 TR2010000103W WO2010140992A1 WO 2010140992 A1 WO2010140992 A1 WO 2010140992A1 TR 2010000103 W TR2010000103 W TR 2010000103W WO 2010140992 A1 WO2010140992 A1 WO 2010140992A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
rosuvastatin calcium
composition according
diluent
disintegrant
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
PCT/TR2010/000103
Other languages
English (en)
Inventor
Mahmut Bilgic
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.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of WO2010140992A1 publication Critical patent/WO2010140992A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates

Definitions

  • the present invention relates to pharmaceutical compositions comprising rosuvastatin calcium as active agent and at least 60% of lactose as stabilizing agent.
  • Rosuvastatin calcium which is also known as (E)-7-[4-(4-fluorophenyl)-6- isopropyl -2- [methyl (methylsulphonyl) amino]pyrimidyn-5-yl]-(3R,5S)-3,5-Dihydroxyhept-6-enoic acid] calcium salt was first described in EP0521471.
  • the compound is defined as an inhibitor of 3- hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) and indicated for treatment of hyperlipidproteinemia, aterosclerosis and hypercholesterolemia.
  • HMG CoA reductase 3- hydroxy-3-methylglutaryl CoA reductase
  • rosuvastatin calcium is conversion of this compound into lactone through "intramolecular esterification" reaction that takes place between the carboxylic acid in this compound and the hydroxyl groups that are present on the ⁇ and ⁇ carbons.
  • the reaction takes place in acidic medium and basic agents reverse the reaction. This phenomenon decreases the stability of the compound and as a result lowers the shelf-life of the product.
  • EP0547000 relates to a stable formulation comprising 7-substituted-3,5- dihydroxy-6-heptanoic acid derivatives.
  • the patent discloses use of a basic agent such as carbonates to prepare pharmaceutical compositions whose aqueous solution has a pH of 8, in order to solve the abovementioned problem and to prevent this unwanted reaction that takes place at low pH values.
  • the aim of the method is to prevent lactone formation and as a result prevent degradation of the active agent.
  • Patents numbered WO 01/54668 and WO 01/54669 are the formulation patents of the product that is sold with the tradename "Crestor”.
  • the patent document disclosed that adjusting the pH is not enough and to solved the abovementioned problem by using tribasic phosphate salts wherein the cation is multivalent (e.g. tribasic calcium phosphate, tribasic magnesium phosphate, tribasic aluminum phosphate) to stabilize pharmaceutical compositions comprising rosuvastatin calcium.
  • tribasic phosphate salts wherein the cation is multivalent e.g. tribasic calcium phosphate, tribasic magnesium phosphate, tribasic aluminum phosphate
  • crestor contains tribasic calcium phosphate as stabilizing agent.
  • the patent application numbered WO 2008/035128 discloses use of magnesium hydroxide and/or calcium acetate as stabilizing agents for preperation of formulations comprising amorphous rosuvastatin calcium.
  • the methods for solving the stability problem of pharmaceutical compositions comprising rosuvastatin calcium are generally directed to use of basic agents.
  • a general problem about use of basic agents is the fact that pharmaceutical compositions comprising these agents effect the mucus membrane of stomach and damage the digestive system upon long-term use for treatment of chronic diseases, such as for treatment of chronic heart diseases.
  • present invention relates to stable pharmaceutical compositions of rosuvastatin calcium which comprise at least 60% lactose, processes for preparation this composition, and use of the prepared composition for treatment.
  • rosuvastatin formulations which can remain stable for longer periods.
  • formulations comprising at least 60% of lactose with respect to the total weight of the composition are found to be more stable when compared to the known formulations.
  • Lactose which is used as a stabilizing agent in the formulations has a lower price than its alternatives in the market and this condition decreases the cost of the final medication.
  • first aspect of the invention is a pharmaceutical composition comprising rosuvastatin calcium and at least 60% of lactose.
  • the second aspect of the inveention is use of at least 60% of lactose to stabilize and to increase the shelf life of rosuvastatin calcium.
  • compositions comprising rosuvastatin calcium and at least 60 % lactose and additionally a diluent, at least one disintegrant, at least one lubricant and other pharmaceutically acceptable excipients.
  • Rosuvastatin calcium that is used as an active agent is used in a stable form, preferably in amorphous form.
  • Diluent can be selected from a group consisting of dibasic sodium phosphate, starch, cellulose derivatives, mannitol, sorbitol, sucrose, lactitol.
  • dibasic calcium phosphate more preferably dibasic calcium phosphate monohydrate is used.
  • Disintegrant can be selected from a group consisting of croscarmellose sodium, crospovidone, polyvinylpyrrolidone, sodium starch glycolate, maize starch, microcrystalline cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose. Disintegrant is preferably crospovidone or microcrystalline cellulose or a mixture thereof.
  • Lubricant can be chosen from a group consisting of magnesium stearate, stearic acid, palmitic acid, calcium stearate, talc, carnuba wax, hydrogenated vegetable oil, mineral oil, polyethylene glycols, sodium stearyl fumarate.
  • magnesium stearate is used.
  • additional excipients such as antioxidants, protecting agents, glidants, silica flow agents can be used, however the excipients that can be used should not be limited with this.
  • Rosuvastatin calcium can be present in the composition in an amount of 1-50%, preferably in an amount of 1-35%, more preferably in an amount of 2-18% with respect to the total weight of the tablet composition.
  • Lactose that is used as a stabilizing agent is typically present in the composition in an amount of 60-90 %, preferably in an amount of 65-85% and more preferably in an amount of 70-85 % with respect to the total weight of the tablet composition.
  • diluent is present in an amount of 1-15 %, preferably in an amount of 1-10% and more preferably in an amount of 1-3% with respect to the total weight of the composition.
  • one or more disintegrant is present in an amount of 1-15% with respect to the total weight of the composition.
  • one or more lubricant can be present in an amount of 1-5% with respect to the total weight of the composition.
  • composition of the present invention can be prepared by using the techniques and processes known in the state of the art such as dry blending of the components. For example; rosuvastatin calcium and at least 60% by weight lactose, are mixed togather with a diluent, one or more disintegrants and other excipients. Prior to mixing the components or the composition itself is sieved thorugh a sieve which has mesh size of 20-40. Lubricant is added to the mixture and the composition is mixed until a homogenous mixture is obtained. After the mixing process the composition is compressed to obtain tablet.
  • the tablets obtained are coated with water based film coating solution by using sprey coating method.
  • the coating can contain, for example polyethylene glycol, ferric oxide, polyvinyl alcohol, lecithin and talc.
  • the coating agent can be chosen from commercially available agents.
  • the coating agent comprises 1-10% preferably 2-
  • Another aspect of the invention is related to a process for prepration of stable pharmaceutical composition comprising rosuvastatin calcium and at least 60% lactosee by weight. Said process comprises addition of at least 60% of lactose into pharmaceutical composition.
  • Rosuvastatin calcium, microcrystalline cellulose, lactose D.C. , dibasic calcium phosphate and crospovidon are mixed for 10 minutes.
  • the mixture is then passed through 25 mesh sieve and then magnesium stearate is added to the sieved mixture and mixed for 5 more minutes.
  • the homegenous mixture obtained at the end of this process is compressed to obtain tablets.
  • the tablets may optionally be coated with conventional methods.
  • the increase in weight of the tablet is in an amount of 1-5%, preferably 2-4% as a result of the coating process

Landscapes

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

Abstract

La présente invention concerne des compositions pharmaceutiques stables de calcium rosuvastatine qui comprennent au moins 60 % de lactose, des procédés pour la préparation de ces compositions, et l'utilisation desdites compositions préparées pour un traitement.
PCT/TR2010/000103 2009-06-03 2010-05-27 Compositions pharmaceutiques stables contenant du calcium rosuvastatine Ceased WO2010140992A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2009/04341 2009-06-03
TR2009/04341A TR200904341A2 (tr) 2009-06-03 2009-06-03 Rosuvastatin kalsiyum içeren kararlı farmasötik bileşimler.

Publications (1)

Publication Number Publication Date
WO2010140992A1 true WO2010140992A1 (fr) 2010-12-09

Family

ID=43020424

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2010/000103 Ceased WO2010140992A1 (fr) 2009-06-03 2010-05-27 Compositions pharmaceutiques stables contenant du calcium rosuvastatine

Country Status (2)

Country Link
TR (1) TR200904341A2 (fr)
WO (1) WO2010140992A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101302306B1 (ko) 2011-01-26 2013-09-03 씨제이제일제당 (주) 고지혈증 복합제
CN104434826A (zh) * 2014-11-08 2015-03-25 鲁南贝特制药有限公司 一种瑞舒伐他汀钙分散片

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0521471A1 (fr) 1991-07-01 1993-01-07 Shionogi Seiyaku Kabushiki Kaisha Dérivés de pyrimidine comme inhibiteurs de la HMG-CoA reductase
EP0547000A1 (fr) 1991-12-12 1993-06-16 Sandoz Ltd. Compositions stabilisées contenant des inhibiteurs de réductase de HMG-CoA
WO2001054669A1 (fr) 2000-01-26 2001-08-02 Astrazeneca Ab Compositions pharmaceutiques renfermant un inhibiteur de la hmg coa reductase
WO2008035128A1 (fr) 2006-09-18 2008-03-27 Richter Gedeon Nyrt. Compositions pharmaceutiques contenant de la rosuvastatine calcique
WO2008062476A2 (fr) * 2006-10-31 2008-05-29 Glenmark Pharmaceutical Limited Composition pharmaceutique comprenant de la rosuvastatine ou un sel de qualité pharmaceutique de cette substance
WO2008075320A2 (fr) * 2006-12-21 2008-06-26 Ranbaxy Laboratories Limited Compositions pharmaceutiques antilipidémiques et leur procédé de préparation
WO2009010787A2 (fr) * 2007-07-13 2009-01-22 Generics [Uk] Limited Compositions stables
WO2010006451A1 (fr) * 2008-07-15 2010-01-21 Pharmascience Inc. Forme galénique contenant une statine
WO2010030201A2 (fr) * 2008-09-09 2010-03-18 Zaklady Farmaceutyczne Polpharma Sa Composition pharmaceutique orale stable contenant un sel pharmaceutiquement acceptable de l'acide [(e)-7-[4-(4-fluorophényl)-6-isopropyl-2-[méthyl(méthylsulfonyl)amino]pyrimidin-5-yl]-(3r,5s)-3,5-dihydroxyhept-6-énoïque
EP2233133A1 (fr) * 2009-03-17 2010-09-29 Sanovel Ilac Sanayi ve Ticaret A.S. Compositions stables comprenant de Rosuvastatine

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0521471A1 (fr) 1991-07-01 1993-01-07 Shionogi Seiyaku Kabushiki Kaisha Dérivés de pyrimidine comme inhibiteurs de la HMG-CoA reductase
EP0547000A1 (fr) 1991-12-12 1993-06-16 Sandoz Ltd. Compositions stabilisées contenant des inhibiteurs de réductase de HMG-CoA
WO2001054669A1 (fr) 2000-01-26 2001-08-02 Astrazeneca Ab Compositions pharmaceutiques renfermant un inhibiteur de la hmg coa reductase
WO2001054668A1 (fr) 2000-01-26 2001-08-02 Astrazeneca Ab Compositions pharmaceutiques renfermant un inhibiteur de la hmg reductase
WO2008035128A1 (fr) 2006-09-18 2008-03-27 Richter Gedeon Nyrt. Compositions pharmaceutiques contenant de la rosuvastatine calcique
WO2008062476A2 (fr) * 2006-10-31 2008-05-29 Glenmark Pharmaceutical Limited Composition pharmaceutique comprenant de la rosuvastatine ou un sel de qualité pharmaceutique de cette substance
WO2008075320A2 (fr) * 2006-12-21 2008-06-26 Ranbaxy Laboratories Limited Compositions pharmaceutiques antilipidémiques et leur procédé de préparation
WO2009010787A2 (fr) * 2007-07-13 2009-01-22 Generics [Uk] Limited Compositions stables
WO2010006451A1 (fr) * 2008-07-15 2010-01-21 Pharmascience Inc. Forme galénique contenant une statine
WO2010030201A2 (fr) * 2008-09-09 2010-03-18 Zaklady Farmaceutyczne Polpharma Sa Composition pharmaceutique orale stable contenant un sel pharmaceutiquement acceptable de l'acide [(e)-7-[4-(4-fluorophényl)-6-isopropyl-2-[méthyl(méthylsulfonyl)amino]pyrimidin-5-yl]-(3r,5s)-3,5-dihydroxyhept-6-énoïque
EP2233133A1 (fr) * 2009-03-17 2010-09-29 Sanovel Ilac Sanayi ve Ticaret A.S. Compositions stables comprenant de Rosuvastatine

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101302306B1 (ko) 2011-01-26 2013-09-03 씨제이제일제당 (주) 고지혈증 복합제
CN104434826A (zh) * 2014-11-08 2015-03-25 鲁南贝特制药有限公司 一种瑞舒伐他汀钙分散片

Also Published As

Publication number Publication date
TR200904341A2 (tr) 2010-12-21

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