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WO2008118031A1 - Composition pharmaceutique comprenant du candésartan cilexétil et procédé de fabrication - Google Patents

Composition pharmaceutique comprenant du candésartan cilexétil et procédé de fabrication Download PDF

Info

Publication number
WO2008118031A1
WO2008118031A1 PCT/PL2008/000026 PL2008000026W WO2008118031A1 WO 2008118031 A1 WO2008118031 A1 WO 2008118031A1 PL 2008000026 W PL2008000026 W PL 2008000026W WO 2008118031 A1 WO2008118031 A1 WO 2008118031A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
candesartan cilexetil
polyethylene glycol
polyvinyl alcohol
graft copolymer
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/PL2008/000026
Other languages
English (en)
Inventor
Marta Wenclaw
Jolanta Haase
Mariusz Siwek
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.)
Zaklady Farmaceutyczne Polpharma SA
Original Assignee
Zaklady Farmaceutyczne Polpharma SA
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
Priority claimed from PL382080A external-priority patent/PL207244B1/pl
Application filed by Zaklady Farmaceutyczne Polpharma SA filed Critical Zaklady Farmaceutyczne Polpharma SA
Priority to EP08741767A priority Critical patent/EP2139456A1/fr
Publication of WO2008118031A1 publication Critical patent/WO2008118031A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles

Definitions

  • composition comprising candesartan cilexetil and method for manufacturing thereof
  • the subject of the invention includes a pharmaceutical composition
  • a pharmaceutical composition comprising candesartan cilexetil as the active pharmaceutical ingredient and graft copolymer of polyvinyl alcohol with polyethylene glycol as a stabilising agent as well as the method for manufacturing thereof.
  • the method for manufacturing of the composition consists in the formation of candesartan cilexetil dispersion with one or more water soluble polymers in the solution of a binder, granulation, drying and granulate tableting.
  • a pharmaceutical composition was disclosed comprising candesartan cilexetil with fatty substances acting as stabilising agents.
  • the fatty substances listed in the publication include phospholipids, fatty acids and their esters.
  • the method for manufacturing of the composition consists in the formation of candesartan cilexetil dispersion with one or more fatty substances in the solution of a binder, granulation, drying and granulate tableting.
  • the objective of the present invention is to develop a new, stable pharmaceutical composition comprising candesartan cilexetil as the active pharmaceutical ingredient whose manufacturing process is simple and may be conducted using standard formulation methods.
  • a graft copolymer of polyvinyl alcohol with polyethylene glycol originally meant as a" coating agent for rapid disintegration tablets, ensures stability of pharmaceutical compositions comprising candesartan cilexetil.
  • the solution of the graft copolymer of polyvinyl alcohol with polyethylene glycol used as a granulating agent during the manufacturing process compensates for the negative properties of the candesartan cilexetil active pharmaceutical ingredient which consist in its electrostatic behaviour and fluffiness which result in the uncontrolled loss of the active pharmaceutical ingredient during the manufacturing process.
  • the graft copolymer of polyvinyl alcohol with polyethylene glycol present in the pharmaceutical composition according to the present invention has a melting point of between 150° and 300°C, preferably between 180° and 250°C, more preferably between 200° and 220°C.
  • the pharmaceutical composition according to the present invention has a content of candesartan cilexetil in the weight ratio to the graft copolymer of polyvinyl alcohol with polyethylene glycol of 4:1 to 1 :3, preferably 1 :2 to 2:1.
  • the pharmaceutical composition according to the present invention comprisies pharmaceutically acceptable excipients selected from a group comprising fillers, binders, disintegrants, lubricants and optionally colourants. It may additionally comprise another active pharmaceutical ingredient acting as a diuretic.
  • the graft copolymer of polyvinyl alcohol with polyethylene glycol present in the pharmaceutical composition according to the present invention has hydrophilic properties.
  • it is the known copolymer under the trade name of Kollicoat® IR comprising 75% polyvinyl alcohol residues and 25% polyethylene glycol residues.
  • the molecular weight of the copolymer is approximately 45,000 Daltons with a melting point of 209°C.
  • Kollicoat® IR is hydrophilic powder readily soluble in water, white to light yellow. To improve its flow, approximately 0.3% of colloidal silica is added.
  • the fillers in the pharmaceutical composition according to the present invention are selected from a group comprising lactose, starch, cellulose, mannitol, sorbitol, tricalcium phosphate, calcium carbonate or other pharmaceutically acceptable fillers or their combination.
  • the binders in the pharmaceutical composition according to the present invention are selected from a group comprising hydroxypropylcellulose, povidone, hydroxypropylmethylcellulose or other pharmaceutically acceptable binders or their combination.
  • the disintegrants in the pharmaceutical composition according to the present invention are selected from a group comprising carmellose sodium or calcium, croscarmellose sodium, crospovidone, sodium starch glycolate or other pharmaceutically acceptable disintegrants or their combination.
  • the lubricants in the pharmaceutical composition according to the present invention are selected from a group comprising magnesium stearate, calcium stearate, stearyl fumarate, stearic acid or other pharmaceutically acceptable lubricants or their combination.
  • the colourants in the pharmaceutical composition according to the present invention are selected from a group comprising iron oxides or other pharmaceutically acceptable colourants or their combination.
  • the other active pharmaceutical ingredient acting as a diuretic in the pharmaceutical composition according to the present invention is hydrochlorothiazide.
  • the pharmaceutical composition according to the present invention is preferably a solid, oral pharmaceutical form, preferably tablet, capsule or powder.
  • the invention includes a method for manufacturing of a pharmaceutical composition comprising candesartan cilexetil as the active pharmaceutical ingredient.
  • the process comprises three steps.
  • a mixture comprising candesartan cilexetil, filler and binder is wet granulated with the solution of the graft copolymer of polyvinyl alcohol with polyethylene glycol acting as a granulating agent with optionally addition of a colourant.
  • the resulting granulate is dried.
  • a disintegrant and optionally another active pharmaceutical ingredient selected from diuretics, optionally a colourant, and a lubricant are added to the dried granulate and the resulting mixture is tableted.
  • the first step of the method for manufacturing of the pharmaceutical composition according to the invention is preferably carried out using fluid bed granulation method with the aqueous solution of the graft copolymer of polyvinyl alcohol with polyethylene glycol acting as a granulating agent with optionally addition of the colourant.
  • the granulating solution constitutes 15% to 100% of the dry mass subjected to granulation, preferably 25% to 50%.
  • the fillers utilised in the step are selected from a group comprising lactose, starch, cellulose, mannitol, sorbitol, tricalcium phosphate, calcium carbonate or other pharmaceutically acceptable fillers or their combination.
  • the binders utilised in the step are selected from a group comprising hydroxypropylcellulose, povidone, hydroxypropylmethylcellulose or other pharmaceutically acceptable binders or their combination.
  • the graft copolymer of polyvinyl alcohol with polyethylene glycol utilised in the step has a melting point of between 150° and 300°C, preferably between 180° and 250°C, more preferably between 200° and 220 0 C.
  • the colourants utilised in the step are selected from a group comprising iron oxides or other pharmaceutically acceptable colourants or their combination.
  • the second step of the method for manufacturing of the pharmaceutical composition according to the present invention is preferably carried out using fluid-bed drying until the moisture content is below 2%, preferably below 1%.
  • the third step of the method for manufacturing of the pharmaceutical composition according to the present invention is carried out by using a disintegrant selected from a group comprising carmellose sodium or calcium, croscarmellose sodium, crospovidone, sodium starch glycolate or other pharmaceutically acceptable disintegrants or their combination.
  • a disintegrant selected from a group comprising carmellose sodium or calcium, croscarmellose sodium, crospovidone, sodium starch glycolate or other pharmaceutically acceptable disintegrants or their combination.
  • the other active pharmaceutical ingredient selected from diuretics used in this step is hydrochlorothiazide.
  • the colourants utilised in the step are selected from a group comprising iron oxides or other pharmaceutically acceptable colourants or their combination.
  • the lubricants used in this step are selected from a group comprising magnesium stearate, calcium stearate, stearyl fumarate, stearic acid or other pharmaceutically acceptable lubricants or their combination.
  • the method for manufacturing of the pharmaceutical composition according to the present invention is characterised by the use of candesartan cilexetil active pharmaceutical ingredient in the weight ratio to the graft copolymer of polyvinyl alcohol with polyethylene glycol of 4:1 to 1 :3, preferably between 1 :2 and 2:1.
  • the Kollicoat® IR and iron oxide in the GLATT GPCG3 fluid-bed granulator The resulting granulate is dried using fluid-bed method. The weighed quantity of carmellose calcium is added to the dried granulate. The content is mixed and weighed magnesium stearate is added. The content is again thoroughly mixed. The resulting tablet mass is tableted using the Kilian SlOO rotary tablet press. 8 mm flat-concave punches are used in the tableting process. The resulting tablets have a weight of 200 mg.
  • Example 5 Magnesium stearate 0.9 Procedure identical to that in Example 1. The resulting tablets have a weight of 200 mg.
  • Kollicoat® IR in the GLATT GPCG3 fluid-bed granulator.
  • the resulting granulate is dried using fluid-bed method.
  • the weighed quantity of carmellose calcium, hydrochlorothiazide and iron oxide is added to the dried granulate.
  • the content is mixed and weighed magnesium stearate is added.
  • the content is again thoroughly mixed.
  • the resulting tablet mass is tableted using the Kilian SlOO rotary tablet press. 8 mm flat-concave punches are used in the tableting process.
  • the resulting tablets have a weight of 200 mg.
  • Example 2 Procedure identical to that in Example 1.
  • the tablets are manufactured without Kollicoat® IR.
  • the quantity of lactose monohydrate is increased to 64% of the single tablet weight.
  • Example 1 Procedure identical to that in Example 6.
  • the tablets are manufactured without Kollicoat® IR.
  • the quantity of lactose monohydrate is increased to 63.25% of the single tablet weight.
  • the stability tests are performed in stability chamber for four weeks, 50°C and 75% RH.
  • the tablets are tested for candesartan cilexetil content and stability using assay methods based on high-performance liquid chromatography.
  • the results of the testing, which confirm the subject matter of the invention, are specified in Table 1 and Table 2.

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

Abstract

Composition pharmaceutique stable comprenant du candésartan celixétil à titre d'ingrédient pharmaceutique actif et un copolymère greffé d'alcool polyvinylique avec un polyéthylène glycol à titre de stabilisant. Le procédé de fabrication de cette composition pharmaceutique comprenant du candésartan celixétil à titre d'ingrédient pharmaceutique actif comprend les étapes suivantes : - un mélange comprenant le candésartan cilexétil, une charge et un liant est granulé par un procédé par voie humide, la solution du copolymère greffé d'alcool polyvinylique avec le polyéthylène glycol servant d'agent de granulation, avec éventuellement ajout d'un colorant, - le granulat résultant est séché, - un délitant et éventuellement un autre ingrédient pharmaceutique actif sélectionné parmi les diurétiques, éventuellement un colorant, et un lubrifiant sont ajoutés au granulat séché et le mélange résultant est homogénéisé, puis mis en comprimés.
PCT/PL2008/000026 2007-03-28 2008-03-28 Composition pharmaceutique comprenant du candésartan cilexétil et procédé de fabrication Ceased WO2008118031A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP08741767A EP2139456A1 (fr) 2007-03-28 2008-03-28 Composition pharmaceutique comprenant du candésartan cilexétil et procédé de fabrication

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
PL382080A PL207244B1 (pl) 2007-03-28 2007-03-28 Doustna kompozycja farmaceutyczna zawierająca kandesartan cyleksetylu oraz sposób jej wytwarzania
PLP.382080 2007-03-28
PLP.384680 2008-03-12
PL384680A PL384680A1 (pl) 2007-03-28 2008-03-12 Kompozycja farmaceutyczna zawierająca kandesartan cyleksetylu oraz sposób jej wytwarzania

Publications (1)

Publication Number Publication Date
WO2008118031A1 true WO2008118031A1 (fr) 2008-10-02

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/PL2008/000026 Ceased WO2008118031A1 (fr) 2007-03-28 2008-03-28 Composition pharmaceutique comprenant du candésartan cilexétil et procédé de fabrication

Country Status (4)

Country Link
EP (1) EP2139456A1 (fr)
PL (1) PL384680A1 (fr)
RU (1) RU2009139485A (fr)
WO (1) WO2008118031A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101632678B (zh) * 2009-09-01 2011-09-14 严洁 一种氯沙坦钾氢氯噻嗪组合物及其制备方法
JP2013075833A (ja) * 2011-09-29 2013-04-25 Nihon Generic Co Ltd カンデサルタンシレキセチルを含有する固形製剤
CN110638764A (zh) * 2019-09-23 2020-01-03 珠海润都制药股份有限公司 一种坎地沙坦酯速释小丸
CN117442577A (zh) * 2023-12-21 2024-01-26 山东则正医药技术有限公司 一种坎地沙坦酯微片及制备方法和应用
EP4440551A1 (fr) * 2021-12-02 2024-10-09 Basf Se Composition auxiliaire de compression directe

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004052345A1 (fr) * 2002-12-11 2004-06-24 Ranbaxy Laboratories Limited Composition pour enrobage de masquage de gout et procedes d'application de ladite composition
WO2005070398A2 (fr) * 2004-01-23 2005-08-04 Ranbaxy Laboratories Limited Compositions pharmaceutiques de candesartan cilexetil stabilisees par des co-solvants
WO2005079751A2 (fr) * 2004-01-23 2005-09-01 Ranbaxy Laboratories Limited Compositions pharmaceutiques orales de candesartan cilexetil
WO2005084648A1 (fr) * 2004-02-27 2005-09-15 Ranbaxy Laboratories Limited Compositions pharmaceutiques comprenant du candesartan cilexetil

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004052345A1 (fr) * 2002-12-11 2004-06-24 Ranbaxy Laboratories Limited Composition pour enrobage de masquage de gout et procedes d'application de ladite composition
WO2005070398A2 (fr) * 2004-01-23 2005-08-04 Ranbaxy Laboratories Limited Compositions pharmaceutiques de candesartan cilexetil stabilisees par des co-solvants
WO2005079751A2 (fr) * 2004-01-23 2005-09-01 Ranbaxy Laboratories Limited Compositions pharmaceutiques orales de candesartan cilexetil
WO2005084648A1 (fr) * 2004-02-27 2005-09-15 Ranbaxy Laboratories Limited Compositions pharmaceutiques comprenant du candesartan cilexetil

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JANSSENS ET AL: "The use of a new hydrophilic polymer, Kollicoat IR<(>R), in the formulation of solid dispersions of Itraconazole", EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, ELSEVIER, AMSTERDAM, NL, vol. 30, no. 3-4, 23 February 2007 (2007-02-23), pages 288 - 294, XP005901598, ISSN: 0928-0987 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101632678B (zh) * 2009-09-01 2011-09-14 严洁 一种氯沙坦钾氢氯噻嗪组合物及其制备方法
JP2013075833A (ja) * 2011-09-29 2013-04-25 Nihon Generic Co Ltd カンデサルタンシレキセチルを含有する固形製剤
CN110638764A (zh) * 2019-09-23 2020-01-03 珠海润都制药股份有限公司 一种坎地沙坦酯速释小丸
EP4440551A1 (fr) * 2021-12-02 2024-10-09 Basf Se Composition auxiliaire de compression directe
CN117442577A (zh) * 2023-12-21 2024-01-26 山东则正医药技术有限公司 一种坎地沙坦酯微片及制备方法和应用
CN117442577B (zh) * 2023-12-21 2024-03-15 山东则正医药技术有限公司 一种坎地沙坦酯微片及制备方法和应用

Also Published As

Publication number Publication date
EP2139456A1 (fr) 2010-01-06
RU2009139485A (ru) 2011-05-10
PL384680A1 (pl) 2008-09-29

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