WO2012153181A1 - Composition pharmaceutique comprenant de la pitavastatine ou ses sels pharmaceutiquement acceptables - Google Patents

Composition pharmaceutique comprenant de la pitavastatine ou ses sels pharmaceutiquement acceptables Download PDF

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Publication number
WO2012153181A1
WO2012153181A1 PCT/IB2012/000911 IB2012000911W WO2012153181A1 WO 2012153181 A1 WO2012153181 A1 WO 2012153181A1 IB 2012000911 W IB2012000911 W IB 2012000911W WO 2012153181 A1 WO2012153181 A1 WO 2012153181A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
pitavastatin
alkali metal
lactose
astm
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/IB2012/000911
Other languages
English (en)
Inventor
Ferhat FARSI
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.)
Abdi Ibrahim Ilac Sanayi Ve Ticaret AS
Original Assignee
Abdi Ibrahim Ilac Sanayi Ve Ticaret AS
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 Abdi Ibrahim Ilac Sanayi Ve Ticaret AS filed Critical Abdi Ibrahim Ilac Sanayi Ve Ticaret AS
Publication of WO2012153181A1 publication Critical patent/WO2012153181A1/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
    • A61K31/435—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
    • A61K31/47—Quinolines; Isoquinolines
    • 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
    • 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 pharmaceutical composition
  • a pharmaceutical composition comprising pitavastatin or its pharmaceutically acceptable salts, where such composition has high stability and a good dissolution profile.
  • the disclosed pharmaceutical composition is preferably in an oral dosage form such as a tablet, a capsule, a pellet, a minitablet, etc.
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising pitavastatin calcium, which is chemically known as (+)monocalcium bis ⁇ (3R, 5S, 6E)-7- [2-cyclopropyl-4-(4-fluorophenyl)-3 -quinolyl] -3 ,5 -dihydroxy-6-heptenoate ⁇ as presented below in structural formula "Formula F.
  • Pitavastatin calcium is sold under the trade name LIVALO® in the US and is a synthetic lipid lowering agent. Pitavastatin is used in the treatment of hypercholesterolemia and mixed dyslipidemia.
  • European Patent No. 0814782 Bl discloses a pharmaceutical composition comprising pitavastatin or its salt or ester, to which a basic substance is added so that the aqueous solution or dispersion of the composition has a pH from 7 to 7.8 when it is dispersed in water.
  • U.S. Patent No. 6,465,477 discloses a pharmaceutical composition comprising pitavastatin or its salt or ester, to which a basic substance is added so that the aqueous solution or dispersion of the composition has a pH from 6 to 7.8 when it is dispersed in water.
  • the same patent also discloses pitavastatin and its salts and esters which are unstable in a high pH range.
  • impurities in formulations containing them include residual amounts of synthetic precursors to the active agent, by- products which arise during synthesis of the active agent, residual solvents, isomers of the active agent, excipients used in the preparation of the pharmaceutical formulation, and unidentified adventitious substances.
  • Other impurities which may appear on storage include substances resulting from degradation of the active agent, for instance, by oxidation or hydrolysis.
  • the present invention discloses a pharmaceutical composition
  • a pharmaceutical composition comprising a therapeutically effective amount of pitavastatin and a base, wherein the pH of the composition is more than or equal to 9.0.
  • the present invention discloses a process for preparing a pharmaceutical composition of pitavastatin involving direct compression comprising the steps of;
  • the pitavastatin tablet obtained in Ste (2) is coated.
  • the present invention discloses a process for the preparation of a pharmaceutical composition of pitavastatin calcium obtained by the above process, where the composition obtained is free of process related impurities.
  • the present invention discloses a process for the preparation of a pharmaceutical composition of pitavastatin calcium by direct compression which is free of impurities.
  • the present invention discloses a pharmaceutical composition of pitavastatin calcium prepared by the above process, where the composition obtained has a longer shelf life period without increase in any impurities.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a therapeutically effective amount of pitavastatin and a base, where in the pH of the composition is more than or equal to 9.0
  • therapeutically effective amount means the amount of a compound that, when administered to a mammal for treating a state, disorder or condition is sufficient to effect such treatment.
  • the therapeutically effective amount will vary depending on the compound, the disease and its severity as well as the age, weight, physical condition and responsiveness of the mammal to be treated.
  • the present invention discloses a pharmaceutical composition
  • a pharmaceutical composition comprising a therapeutically effective amount of pitavastatin and a base, where the pH of the composition is equal to or more than 9.0.
  • Suitable base used to make the pH of the composition more than or equal to 9 includes (but is not limited to) organic bases, inorganic bases and their mixtures thereof.
  • Suitable inorganic bases include (but are not limited to) alkali metal carbonates (such as sodium carbonate, potassium carbonate, calcium carbonate and the like), alkali earth metal bicarbonates (such as sodium bicarbonate, potassium bicarbonate, magnesium bicarbonate and the like), earth alkali metal oxides (such as magnesium oxide or calcium oxide) as well as other similar materials known to those of ordinary skill in the art.
  • Suitable organic bases include meglumine and the like, as well as other similar materials known to those of ordinary skill in the art.
  • the examples set forth herein serve the purpose of aiding in the understanding of the application and are not intended to, and should not be construed to, limit its scope in any way. Such materials are well known to those of ordinary skill in the art and are described in numerous publications.
  • the base may be present in an amount less than 50%, more preferably less than 10%, and more preferably less than 5% by weight based on the total weight of the composition.
  • the present invention discloses a process for preparing a pharmaceutical composition involving direct compression comprising the steps of:
  • Step 1) involves, blending pitavastatin calcium and one or more pharmaceutically acceptable excipients:
  • Suitable pharmaceutically acceptable excipients include (but are not limited to) binders, diluents, disintegrants, surfactants and lubricants.
  • Suitable binders that can be used in Step (1) include (but are not limited to); polyvinylpyrolidone, copovidone, starches such as pregelatinized starch, cellulose derivatives such as hydroxyporpylmethyl cellulose, ethylcellulose, hydroxypropylcellulose and carboxymethylcellulose and their salts, gelatine, acacia, agar, alginic acid, carbomer, chitosan, dextrates, dextrin, glycerol dibehenate, guargum, hypromellose, maltodextrin, poloxamer, polycarbophil, polydextrose, polyethylene oxide, polymethyacrylates, sodium alginate, sucrose, mixtures thereof and the like.
  • Suitable diluents that can be used in Step (1) include (but are not limited to); anhydrous lactose, lactose monohydrate, modified lactose, dibasic calcium phosphate, tribasic calcium phosphate, microcrystalline cellulose, silicified microcrystalline cellulose, powdered cellulose, maize starch, pregelatinized starch, calcium carbonate, sucrose, glucose, dextrates, dextrins, dextrose, fructose, lactitol, mannitol, sorbitol starch, calcium lactate or mixtures of diluents.
  • Suitable disintegrants that can be used in Step (1) include (but are not limited to); starch, pregelatinized starch, microcrystalline cellulose, sodium starch glycolate, crospovidone, croscarmellose sodium, low-substituted hydroxypropyl cellulose, alginic acid, carboxy methyl cellulose sodium, sodium alginate, calcium alginate and chitosan.
  • Suitable lubricants that can be used in Step (1) include (but are not limited to) magnesium stearate, stearic acid, palmitic acid, talc, and aerosil.
  • Suitable surfactants that can be used in Step (1) include (but are not limited to) polysorbate 80, polyoxyethylene sorbitan, polyoxyethylene-polyoxy-propylene copolymer and sodium lauryl sulphate.
  • Step 2) involves, direct compression of the blend from Step (1) into a tablet:
  • the obtained pitavastatin blend with the pharmaceutically acceptable excipients after lubricating the blend, will be directly compressed into suitably sized tablets by direct compression already known in the art.
  • Step 3 involves, optionally, coating on the blend of one or more pharmaceutically acceptable excipients.
  • the tablets may be film coated in a conventional manner, e.g. for appearance, for palatability or for production purposes.
  • Suitable coating compositions include (but are not limited to) binders selected from hydroxypropylcellulose, hydroxyethylmethyl cellulose, povidone, hydroxypropyl cellulose, hydroxyethyl cellulose, low-substituted hydroxypropyl cellulose, hydroxypropylmethyl cellulose acrylate and/or methacrylate co-polymers, resins etc.
  • the coating may be an enteric coating, e.g. which is insoluble in acidic gastric juice but soluble in alkaline digestive juice. Such a coating enables the tablet to pass through the stomach into the duodenum, where it dissolves.
  • a suitable enteric coating might be cellulose acetate phthalate.
  • the coating composition may further include colorants, plasticizers, surfactants and anti-adherents, all of which are widely known in the art.
  • the present disclosure provides pharmaceutical compositions containing dosage forms about 1 mg, 2 mg and 4 mg strength.
  • Such preferred pharmaceutical compositions are administered as an adjunctive therapy to reduce total cholesterol (TC), low density lipoprotein (LDL-C) apolipoprotein B (Apo B), triglycerides ((TG) and to increase HDL-C in adult patients with primary hyperlipidemia and mixed dyslipidemia.
  • TC total cholesterol
  • LDL-C low density lipoprotein
  • Apo B apolipoprotein B
  • TG triglycerides
  • the present invention discloses a process for the preparation of a pharmaceutical composition of pitavastatin calcium obtained by the above process which is free of process related impurities.
  • Pitavastatin calcium obtained according to the process of the present invention is substantially pure.
  • “Substantially pure” means, pitavastatin calcium prepared in accordance with the process of the present invention has a purity of more than 99.5% by weight and contains impurities less than 0.5% by weight, where all process related impurities are taken into account.
  • the present invention discloses a process for the preparation of a pharmaceutical composition of pitavastatin calcium by direct compression which is free of impurities during long term stability.
  • the present invention discloses pitavastatin calcium prepared by the process described above having a longer shelf life period without substantial increase in any impurities.
  • Step (7) Pass the dried granules of Step (7) through ASTM 30 (600 microns) sieve.
  • portion I Sift part quantity of lactose granules (portion I) through ASTM 30 sieve followed by pitavastatin calcium, calcium carbonate and remaining quantity of lactose anhydrous (portion II) and load into granulator.
  • Step (7) Pass the dried granules of Step (7) through ASTM 30 (600 microns) sieve.
  • Step (2) low substituted Hydroxypropyl cellulose, Hydroxypropyl methyl cellulose and remaining quantity of Lactose granules
  • Step (2) low substituted Hydroxypropyl cellulose, Hydroxypropyl methyl cellulose and remaining quantity of Lactose granules
  • step 3 followed by the material of step 3, and remaining quantity of Lactose anhydrous [Portion III] and mix.

Landscapes

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

Abstract

La présente invention concerne une composition pharmaceutique comprenant de la pitavastatine ou ses sels pharmaceutiquement acceptables, ladite composition ayant une stabilité élevée et un bon profil de dissolution.
PCT/IB2012/000911 2011-05-11 2012-05-10 Composition pharmaceutique comprenant de la pitavastatine ou ses sels pharmaceutiquement acceptables Ceased WO2012153181A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TRTR2011/04599 2011-05-11
TR201104599 2011-05-11

Publications (1)

Publication Number Publication Date
WO2012153181A1 true WO2012153181A1 (fr) 2012-11-15

Family

ID=46317445

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2012/000911 Ceased WO2012153181A1 (fr) 2011-05-11 2012-05-10 Composition pharmaceutique comprenant de la pitavastatine ou ses sels pharmaceutiquement acceptables

Country Status (1)

Country Link
WO (1) WO2012153181A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107115306A (zh) * 2017-04-17 2017-09-01 浙江京新药业股份有限公司 一种含匹伐他汀钙的药物组合物及其制备方法
US10835495B2 (en) 2012-11-14 2020-11-17 W. R. Grace & Co.-Conn. Compositions containing a biologically active material and a non-ordered inorganic oxide material and methods of making and using the same
WO2025186785A1 (fr) * 2024-03-08 2025-09-12 TECNIMEDE - Sociedade Técnico-medicinal, SA Composition pharmaceutique orale de pitavastatine, son procédé et ses utilisations

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0336298A1 (fr) * 1988-03-31 1989-10-11 E.R. Squibb & Sons, Inc. Compositions pharmaceutiques ayant une bonne stabilité
EP0547000A1 (fr) * 1991-12-12 1993-06-16 Sandoz Ltd. Compositions stabilisées contenant des inhibiteurs de réductase de HMG-CoA
WO2000035425A1 (fr) * 1998-12-16 2000-06-22 Lek Pharmaceutical And Chemical Company D.D. FORMULATION PHARMACEUTIQUE STABLE COMPRENANT UN INHIBITEUR DE HMG-CoA REDUCTASE
US6465477B1 (en) 1997-08-18 2002-10-15 Kowa Company, Ltd. Stable pharmaceutical composition
EP0814782B1 (fr) 1995-12-22 2002-11-27 Kowa Company Ltd. Composition pharmaceutique stabilisee a l'aide d'un agent de base
WO2004010980A1 (fr) * 2002-07-25 2004-02-05 Novartis Ag Compositions renfermant des inhibiteurs de la reductase hmg-coa
WO2005051346A2 (fr) * 2003-11-26 2005-06-09 Novartis Ag Compositions contenant des composes organiques

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0336298A1 (fr) * 1988-03-31 1989-10-11 E.R. Squibb & Sons, Inc. Compositions pharmaceutiques ayant une bonne stabilité
EP0547000A1 (fr) * 1991-12-12 1993-06-16 Sandoz Ltd. Compositions stabilisées contenant des inhibiteurs de réductase de HMG-CoA
EP0814782B1 (fr) 1995-12-22 2002-11-27 Kowa Company Ltd. Composition pharmaceutique stabilisee a l'aide d'un agent de base
US6465477B1 (en) 1997-08-18 2002-10-15 Kowa Company, Ltd. Stable pharmaceutical composition
WO2000035425A1 (fr) * 1998-12-16 2000-06-22 Lek Pharmaceutical And Chemical Company D.D. FORMULATION PHARMACEUTIQUE STABLE COMPRENANT UN INHIBITEUR DE HMG-CoA REDUCTASE
WO2004010980A1 (fr) * 2002-07-25 2004-02-05 Novartis Ag Compositions renfermant des inhibiteurs de la reductase hmg-coa
WO2005051346A2 (fr) * 2003-11-26 2005-06-09 Novartis Ag Compositions contenant des composes organiques

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10835495B2 (en) 2012-11-14 2020-11-17 W. R. Grace & Co.-Conn. Compositions containing a biologically active material and a non-ordered inorganic oxide material and methods of making and using the same
CN107115306A (zh) * 2017-04-17 2017-09-01 浙江京新药业股份有限公司 一种含匹伐他汀钙的药物组合物及其制备方法
CN107115306B (zh) * 2017-04-17 2019-09-13 浙江京新药业股份有限公司 一种含匹伐他汀钙的药物组合物及其制备方法
WO2025186785A1 (fr) * 2024-03-08 2025-09-12 TECNIMEDE - Sociedade Técnico-medicinal, SA Composition pharmaceutique orale de pitavastatine, son procédé et ses utilisations

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