WO2004085426A1 - Novel crystalline forms of candesartan cilexetil - Google Patents
Novel crystalline forms of candesartan cilexetil Download PDFInfo
- Publication number
- WO2004085426A1 WO2004085426A1 PCT/IN2003/000090 IN0300090W WO2004085426A1 WO 2004085426 A1 WO2004085426 A1 WO 2004085426A1 IN 0300090 W IN0300090 W IN 0300090W WO 2004085426 A1 WO2004085426 A1 WO 2004085426A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- candesartan cilexetil
- dioxane
- ray powder
- powder diffraction
- diffraction pattern
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
Definitions
- the present invention relates to two novel crystalline forms and a novel
- Candesartan cilexetil is an antihypertensive agent and its therapeutic uses were disclosed in US 5,196,444. US 5,196,444 also disclosed a crystalline form of candesartan cilexetil (C-type crystalline form). Two crystalline forms of candesartan cilexetil, form I and form II, are described in Chem. Pharm. Bull. 47(2), 182-186 (1999).
- the object of the present invention is to provide a stable novel 1 ,4- dioxane solvate of candesartan cilexetil and two stable crystalline forms of candesartan cilexetil, processes for preparing these forms and pharmaceutical compositions containing them.
- One aspect of the present invention is to provide a novel 1 ,4-dioxane solvate of candesartan cilexetil (hereinafter referred to as candesartan cilexetil dioxane solvate).
- candesartan cilexetil dioxane solvate typically the content of 1 ,4-dioxane in the solvate is 8.8 to 13.0 % w/w.
- the candesartan cilexetil dioxane solvate is characterized by an x- ray powder diffraction pattern having peaks expressed as 2 ⁇ at about 6.0, 10.7, 16.2, 18.0, 19.7, 20.6, 21.3, 21.7, and 22.3 degrees.
- Figure 1 shows typical x- ray powder diffraction pattern of candesartan cilexetil dioxane solvate.
- Candesartan cilexetil dioxane solvate is prepared by dissolving crystalline form or amorphous form of candesartan cilexetil in 1 ,4-dioxane and crystallizing at 5°C to15°C, preferably at 5°C to 10°C.
- Another aspect of the present invention is to provide a novel crystalline form of candesartan cilexetil (hereinafter referred to as candesartan cilexetil form III, characterized by an x-ray powder diffraction pattern having peaks at about 6.3, 7.3, 8.1 , 8.9, 10.1 , 14.6, 15.0, 15.8, and 18.8 degree.
- Figure 2 shows typical x-ray powder diffraction pattern of candesartan cilexetil form III.
- the candesartan cilexetil form III is prepared by dissolving candesartan cilexetil in toluene by heating, cooling the solution slowly to 0°C to 5°C, maintaining at 0°C to 5°C for about 1 hour and separating the crystals formed by filtration.
- the solvent may be heated to dissolve candesartan cilexetil.
- Candesartan cilexetil used in the process may be any of the crystalline forms except form III, amorphous form or candesartan cilexetil dioxane solvate.
- candesartan cilexetil form IV Another aspect of the present invention is to provide a novel crystalline form of candesartan cilexetil (hereinafter referred to as candesartan cilexetil form IV).
- the candesartan cilexetil form IV is characterized by an x-ray powder diffraction pattern having peaks at about 6.1, 7.1 , 11.6, 11.9, 17.9, 19.8 and 21.2 degree.
- Figure 3 shows typical x-ray powder diffraction pattern of candesartan cilexetil form IV.
- the candesartan cilexetil form IV is prepared by mixing candesartan cilexetil, methyl tert-butyl ether and methanol at 50°C 55°C and maintaining at 20°C to 25°C for about 10 hours.
- Candesartan cilexetil used in the process may be any of the crystalline forms except form IV, amorphous form or candesartan cilexetil dioxane solvate.
- Candesartan cilexetil used in the above processes may be obtained by the known methods.
- a pharmaceutical composition comprising crystalline form III or form IV of candesartan cilexetil and a pharmaceutically acceptable carrier.
- Figure 1 is a x-ray powder diffraction pattern of candesartan cilexetil dioxane solvate.
- Figure 2 is a x-ray powder diffraction pattern of candesartan cilexetil form III.
- Figure 3 is a x-ray powder diffraction pattern of candesartan cilexetil form IV. x-Ray powder diffraction spectrum was measured on a Siemens D5000 x-ray powder diffractometer having a copper-K ⁇ radiation.
- Example 1 Candesartan cilexetil C-type crystalline form (5 gm, obtained by a process described in US 5,196,444) is dissolved in 1,4-dioxane (50 ml) at 25°C. The solution is cooled to 5°C and maintained for 4 hours at about 5°C. The separated solid is filtered to yield 3 gm candesartan cilexetil dioxane solvate.
- Example 2 Candesartan cilexetil C-type crystalline form (5 gm) is added to toluene (25 ml) and heated to reflux. The contents are maintained under reflux for 15 minutes and then cooled slowly to 0°C in 1 hour and maintained at 0°C to 5°C for 1 hour. The separated crystals are collected by filtration to give 3.5 gm candesartan cilexetil form III.
- Example 3 Example 1 is repeated using candesartan cilexetil form III instead of candesartan cilexetil C-type crystalline form to give Candesartan cilexetil dioxane solvate.
- Example 4 The mixture of candesartan cilexetil C-type crystalline form (5 gm), methyl tert-butyl ether (50 ml) is heated to 55°C, methanol (17 ml) is added to the mixture at 55°C and maintained at about this temperature for 1 hour. The contents are cooled to 25°C and maintained at about 25°C for 13 hours. The separated solid is collected by filtration to give 3 gm candesartan cilexetil form IV.
- Example 5 Example 2 is repeated using candesartan cilexetil form IV instead of candesartan cilexetil C-type crystalline form to give Candesartan cilexetil form III.
- Example 6 Example 4 is repeated using candesartan cilexetil dioxane solvate instead of candesartan cilexetil C-type crystalline form to give Candesartan cilexetil form IV.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
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Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/IN2003/000090 WO2004085426A1 (en) | 2003-03-27 | 2003-03-27 | Novel crystalline forms of candesartan cilexetil |
US10/509,141 US7504516B2 (en) | 2003-03-27 | 2003-03-27 | Crystalline forms of candesartan cilexetil |
AU2003230193A AU2003230193A1 (en) | 2003-03-27 | 2003-03-27 | Novel crystalline forms of candesartan cilexetil |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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PCT/IN2003/000090 WO2004085426A1 (en) | 2003-03-27 | 2003-03-27 | Novel crystalline forms of candesartan cilexetil |
Publications (1)
Publication Number | Publication Date |
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WO2004085426A1 true WO2004085426A1 (en) | 2004-10-07 |
Family
ID=33042616
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/IN2003/000090 WO2004085426A1 (en) | 2003-03-27 | 2003-03-27 | Novel crystalline forms of candesartan cilexetil |
Country Status (3)
Country | Link |
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US (1) | US7504516B2 (en) |
AU (1) | AU2003230193A1 (en) |
WO (1) | WO2004085426A1 (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005330277A (en) * | 2004-05-19 | 2005-12-02 | Teva Pharmaceutical Industries Ltd | Candesartan cilexetil polymorph |
WO2005123721A2 (en) * | 2004-06-18 | 2005-12-29 | Ranbaxy Laboratories Limited | Amorphous and polymorphic forms of candesartan cilexetil |
WO2005077941A3 (en) * | 2004-02-11 | 2006-06-22 | Teva Pharma | Candesartan cilexetil polymorphs |
WO2007019448A2 (en) * | 2005-08-08 | 2007-02-15 | Nitromed, Inc. | Nitric oxide enhancing angiotensin ii antagonist compounds, compositions and methods of use |
WO2008035360A2 (en) * | 2006-06-13 | 2008-03-27 | Alembic Limited | Novel crystalline forms of candesartan cilexetil, candesartan, tritylated candesartan and tritylated candesartan cilexetil |
EP1952806A1 (en) | 2007-02-01 | 2008-08-06 | Helm AG | Process for the preparation of adsorbates of candesartan |
JP2009185060A (en) * | 2004-05-19 | 2009-08-20 | Teva Pharmaceutical Industries Ltd | Candesartan cilexetil polymorph |
CN109627234A (en) * | 2019-01-30 | 2019-04-16 | 浙江省食品药品检验研究院 | A kind of candesartan cilexetil crystal and preparation method thereof |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102004060699A1 (en) * | 2004-12-16 | 2006-06-22 | Ratiopharm Gmbh | Process for the preparation of candesartan |
ATE441637T1 (en) * | 2005-02-03 | 2009-09-15 | Ratiopharm Gmbh | METHOD FOR PRODUCING LOSARTAN |
CN102106160B (en) * | 2009-05-25 | 2014-12-31 | 松下电器产业株式会社 | Piezoelectric acoustic transducer |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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US5196444A (en) * | 1990-04-27 | 1993-03-23 | Takeda Chemical Industries, Ltd. | 1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate and compositions and methods of pharmaceutical use thereof |
EP0668272A2 (en) * | 1994-01-28 | 1995-08-23 | Takeda Chemical Industries, Ltd. | A process for the production of tetrazolyl compounds |
EP0881212A1 (en) * | 1997-05-26 | 1998-12-02 | Takeda Chemical Industries, Ltd. | Production method of aminobenzene compound |
Family Cites Families (4)
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DK153787C (en) | 1979-06-01 | 1989-01-16 | Wellcome Found | METHOD OF ANALOGUE FOR THE PREPARATION OF SUBSTITUTED 3,5-DIAMINO-6-PHENYL-1,2,4-TRIAZINES AND ALFA-CYANOBENZYLIDEEN-AMINOGUANIDE COMPOUNDS FOR USE AS INTERMEDIATES |
WO2002068398A1 (en) | 2001-02-27 | 2002-09-06 | Teva Pharmaceutical Industries Ltd. | New crystal forms of lamotrigine and processes for their preparations |
US6992219B2 (en) | 2002-08-09 | 2006-01-31 | Cephalon France | Modafinil polymorphic forms |
EP1603889A1 (en) | 2003-03-17 | 2005-12-14 | Hetero Drugs Limited | Novel crystalline forms of lamotrigine |
-
2003
- 2003-03-27 US US10/509,141 patent/US7504516B2/en not_active Expired - Fee Related
- 2003-03-27 AU AU2003230193A patent/AU2003230193A1/en not_active Abandoned
- 2003-03-27 WO PCT/IN2003/000090 patent/WO2004085426A1/en not_active Application Discontinuation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5196444A (en) * | 1990-04-27 | 1993-03-23 | Takeda Chemical Industries, Ltd. | 1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate and compositions and methods of pharmaceutical use thereof |
EP0668272A2 (en) * | 1994-01-28 | 1995-08-23 | Takeda Chemical Industries, Ltd. | A process for the production of tetrazolyl compounds |
EP0881212A1 (en) * | 1997-05-26 | 1998-12-02 | Takeda Chemical Industries, Ltd. | Production method of aminobenzene compound |
Non-Patent Citations (1)
Title |
---|
HIROKAZU MATSUNAGA ET AL.: "Solid-state characterization of candesartan cilexetil (TCV-116): crystal structure and molecular mobility", CHEMICAL & PHARMACEUTICAL BULLETIN, vol. 47, no. 2, 1999, pages 182 - 186, XP002957606 * |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005077941A3 (en) * | 2004-02-11 | 2006-06-22 | Teva Pharma | Candesartan cilexetil polymorphs |
US7692023B2 (en) | 2004-02-11 | 2010-04-06 | Teva Pharmaceutical Industries Ltd. | Candesartan cilexetil polymorphs |
JP2005330277A (en) * | 2004-05-19 | 2005-12-02 | Teva Pharmaceutical Industries Ltd | Candesartan cilexetil polymorph |
JP2009185060A (en) * | 2004-05-19 | 2009-08-20 | Teva Pharmaceutical Industries Ltd | Candesartan cilexetil polymorph |
WO2005123721A2 (en) * | 2004-06-18 | 2005-12-29 | Ranbaxy Laboratories Limited | Amorphous and polymorphic forms of candesartan cilexetil |
WO2005123721A3 (en) * | 2004-06-18 | 2006-06-08 | Ranbaxy Lab Ltd | Amorphous and polymorphic forms of candesartan cilexetil |
WO2007019448A2 (en) * | 2005-08-08 | 2007-02-15 | Nitromed, Inc. | Nitric oxide enhancing angiotensin ii antagonist compounds, compositions and methods of use |
WO2007019448A3 (en) * | 2005-08-08 | 2009-04-30 | Nitromed Inc | Nitric oxide enhancing angiotensin ii antagonist compounds, compositions and methods of use |
WO2008035360A2 (en) * | 2006-06-13 | 2008-03-27 | Alembic Limited | Novel crystalline forms of candesartan cilexetil, candesartan, tritylated candesartan and tritylated candesartan cilexetil |
WO2008035360A3 (en) * | 2006-06-13 | 2008-10-16 | Alembic Ltd | Novel crystalline forms of candesartan cilexetil, candesartan, tritylated candesartan and tritylated candesartan cilexetil |
EP1952806A1 (en) | 2007-02-01 | 2008-08-06 | Helm AG | Process for the preparation of adsorbates of candesartan |
CN109627234A (en) * | 2019-01-30 | 2019-04-16 | 浙江省食品药品检验研究院 | A kind of candesartan cilexetil crystal and preparation method thereof |
Also Published As
Publication number | Publication date |
---|---|
US20050182114A1 (en) | 2005-08-18 |
US7504516B2 (en) | 2009-03-17 |
AU2003230193A1 (en) | 2004-10-18 |
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