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WO2009072769A2 - Procédé de préparation de risédronate de sodium comme formes anhydres et hydratées - Google Patents

Procédé de préparation de risédronate de sodium comme formes anhydres et hydratées Download PDF

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Publication number
WO2009072769A2
WO2009072769A2 PCT/KR2008/006912 KR2008006912W WO2009072769A2 WO 2009072769 A2 WO2009072769 A2 WO 2009072769A2 KR 2008006912 W KR2008006912 W KR 2008006912W WO 2009072769 A2 WO2009072769 A2 WO 2009072769A2
Authority
WO
WIPO (PCT)
Prior art keywords
hydrate
risedronate sodium
hours
solvent
anhydrous
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/KR2008/006912
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English (en)
Other versions
WO2009072769A3 (fr
Inventor
Jae-Yeon Shin
Young-Deuck Kim
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.)
Dongwoo Syntech Co Ltd
Original Assignee
Dongwoo Syntech Co Ltd
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 Dongwoo Syntech Co Ltd filed Critical Dongwoo Syntech Co Ltd
Priority to EP08857936A priority Critical patent/EP2229397A4/fr
Priority to JP2010536837A priority patent/JP2011506310A/ja
Publication of WO2009072769A2 publication Critical patent/WO2009072769A2/fr
Publication of WO2009072769A3 publication Critical patent/WO2009072769A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/58—Pyridine rings
    • 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
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate

Definitions

  • the present invention relates to a process for preparation of risedronate sodium in anhydrous and hydrate forms.
  • Osteoporosis is a disease causing gradual loss of bone minerals. Treatments for osteoporosis are designed to improve absorption of calcium while reducing urinary calcium excretion.
  • a technical object of the present invention is bisphosphonate such as 2-(3-pyridyl)-l-hydroxyethane-l,l-bis-phosphonic acid (risedronic acid) represented by the following Formula I which is favorably used in treatment of bone diseases and calcium metabolic diseases.
  • Paget' s disease and heterotropic ossification are known to be treated by both ethane- 1 -hydroxy- 1 , 1 -diphosphonic acid and risedronate sodium (I) .
  • Korean Patent Application No. 10-2002-7009790 describes a process for selective crystallization of risedronate sodium in a mono-hydrate or hemipenta- hydrate form wherein risedronate sodium is present in the form of mono-hydrate and/or hemipenta-hydrate and such hydrate form is selectively determined according to crystallization conditions.
  • the above process has problems in controlling nucleation temperature and crystallization rate during mass production of the compound and requires not only pure water but also an additional solvent in large quantities, for example, 30 times that used in the present invention, in order to obtain a particular type hydrate.
  • Korean Patent Application No. 10-2004-7016268 proposes a variety of hydrate forms of risedronate sodium such as A (hemipenta hydrate), B (mono hydrate), BB, Bl, C, D (anhydrous form), E, F, G, H, etc. and their preparation methods, and demonstrates thermogravimetric analysis (TGA) and Fourier Transform Infrared Spectroscopy (FT-IR) results thereof.
  • TGA thermogravimetric analysis
  • FT-IR Fourier Transform Infrared Spectroscopy
  • this patent also involves some problems that prolonged reflux is required, production yield is decreased, a desired reflux temperature must be maintained for a long time during which a hemi-penta hydrate type risendronate sodium is used as a starting material, and an additional solvent is required in an amount of at least 2 times that used in the present invention.
  • the present invention suggests use of risedronate sodium hemipenta hydrate (sometimes, referred to as "2.5 hydrate”) as a starting material to produce a novel hydrate with improved characteristics, compared to conventional methods using risedronic acid as a starting material.
  • the starting material that is, risedronate sodium 2.5 hydrate according to the present invention may be easily prepared as described in the following exemplary embodiments.
  • an object of the present invention is to provide a process for preparing risedronate sodium in a particular hydrate form with high yield in a short time, including: using risedronate sodium 2.5 hydrate as a starting material; and mixing the starting material with water and a small amount of an additional solvent in a predetermined mixing ratio thereof.
  • the present invention provides a novel process for selectively preparing risedronate sodium in hydrate forms available commercially, wherein environmental problems can be eliminated, production yield can be improved and production time can be reduced, by using a small amount of the additional solvent and water in a desired relative ratio.
  • a process for preparing, the starting material as used herein, "risedronate sodium 2.5 hydrate” is disclosed in detail in KR Patent No. 0775440 issued to the present applicant.
  • the present invention is directed to a novel method for preparing risedronate sodium anhydrous, 1 hydrate and 1.5 hydrate from a mixture consisting of risedronate sodium 2.5 hydrate, an organic solvent and water in a specific ratio.
  • the method enables preparation of high yield risedronate sodium hydrates in a simple manner and is thus commercially available.
  • the preparation of risedronate sodium hydrate according to the present invention may be carried out by the following process.
  • risedronate sodium 1 hydrate a) A mixture of a suitable organic solvent and water is added to risedronate sodium 2.5 hydrate. b) The solution is stirred at reflux temperature. c) The reaction solution is cooled, filtered and dried to prepare risedronate sodium 1 hydrate.
  • Organic solvents useful for step (a) include ethanol, methanol, isopropanol, acetonitrile 1,4-dioxane.
  • ethanol and isopropanol may be used.
  • a mixing ratio of the organic solvent and water may be in the range of 6:4 to 9: 1 , preferably about 7:3.
  • the reflux time may be 3 to 7 hours, preferably 5 hours.
  • the cooling temperature may be 15 to 25°C and the cooling time may be 2 to 3 hours.
  • the drying may be carried out under vacuum or hot air at 50 0 C.
  • risedronate sodium 1.5 hydrate a) A mixture of a suitable organic solvent and water are added to risedronate sodium 2.5 hydrate. b) The solution is stirred at an elevated temperature. c) The reaction solution is cooled, filtered and dried to prepare a risedronate sodium 1.5 hydrate.
  • the solvent useful for step (a) may be methanol, ethanol and isopropanol, preferably isopropanol.
  • a mixing ratio of the solvent and water in step (a) may be in the range of 5:5 to 6:4, preferably 6:4.
  • the reaction temperature may be 50 to 70 0 C, preferably 6O 0 C.
  • reaction time may be 6 to 8 hours, preferably 7 hours.
  • step (c) the cooling may be carried out at a temperature of 15 to 25 0 C for 2 to 3 hours, and the drying may be carried out by hot air drying at 4O 0 C.
  • risedronate sodium anhydrous a) A suitable organic solvent is added to risedronate sodium 2.5 hydrate. b) The solution is stirred at a reflux temperature. c) The reaction solution is cooled, filtered and dried to prepare risedronate sodium anhydrous.
  • the solvent may preferably be methanol.
  • the reflux time may be 7 to 20 hours, preferably 12 hours.
  • step (c) the cooling may be carried out at a temperature of 15 to 25°C for 2 to 3 hours, and the drying may be carried out under vacuum at 50 0 C.
  • the risedronate sodium prepared by the method is crystalline 1 hydrate,
  • the moisture content is in the range of 5.5 to 7.5% (by TGA) for 1 hydrate, in the range of 9.0 to 11.0% (by TGA) for 1.5 hydrate, and 1.0% or less (by TGA) for anhydrous.
  • Table 1 shown below shows a variety of analysis data according to a mixing ratio of a solvent and water and reaction temperature.
  • the X-ray diffraction data described herein was obtained by powder diffraction.
  • the X-ray powder diffraction data is obtained by a method well- known in the art using a model provided with a solid detector, PANalytical, X'pert-Pro.
  • X-ray diffraction patterns of the risedronate sodium 1 hydrate are x- ray diffraction peaks plot at 2 ⁇ of 6.0°, 14.3°, 16.5°, 19.6°, 21.8°, 22.8° and 25.4° and X-ray diffraction patterns of the risedronate sodium 1.5 hydrate are x-ray diffraction peaks plot at 20 of 5.9°, 8.8°, 12.2°, 19.7° and 24.5°, and X-ray diffraction patterns of the risedronate sodium anhydrous are X-ray diffraction peaks at 20 of 9.8°, 17.1°, 22.6°, 27.7° and 29.1°.
  • the TGA weight loss as used herein is obtained by calculating a weight loss at a bent of a weight loss curve (See drawings) in the range of at most about 200 ° C to about 220 ° C .
  • Thermogravimetric analysis (TGA) is a thermal analysis method well-known in the art, which measures variations in weight of a sample as a function of temperature. This method is particularly suitable for, for example, decomposition and desolvation. TGA results reported herein were obtained using a TA Instrument, TGA 2950HR. A sample weight as herein used was about 5 mg to about 15 mg.
  • the sample was analyzed by heating at 25 °C to 250 0 C at a heating rate of 10°C/min. An oven was purged with nitrogen gas at a flow rate of 40 rnL/min.
  • the weight loss thus obtained is greater than the level estimated, based on a theoretical moisture content. This is based on the fact that the TGA weight loss process involves decomposition steps.
  • FIG. 1 illustrates X-ray powder diffraction of risedronate sodium 1 hydrate prepared using ethanol as a solvent in Example 2;
  • FIG. 2 illustrates a TGA curve of risedronate sodium 1 hydrate prepared using ethanol as a solvent in Example 2;
  • FIG. 3 illustrates X-ray powder diffraction of risedronate sodium anhydrous prepared using ethanol as a solvent in Example 4.
  • FIG. 4 illustrates a TGA curve of risedronate sodium anhydrous prepared in Example 4.
  • TGA thermogravimetric analysis
  • the present invention provides a method for preparing risedronate sodium hydrates and anhydrous from risedronate sodium 2.5 hydrates as starting materials using a mixture of an organic solvent and water.
  • the present method has advantages of improved yield, low preparation cost and significantly reduced unnecessary by-products, compared to conventional methods. Accordingly, the method is environmentally friendly and thus advantageous in commercial mass-production.

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

Abstract

L'invention concerne un nouveau procédé permettant de préparer des anhydres et des hydrates de risédronate de sodium à partir de 2,5 hydrates de risédronate de sodium comme matériau de départ.
PCT/KR2008/006912 2007-12-07 2008-11-24 Procédé de préparation de risédronate de sodium comme formes anhydres et hydratées Ceased WO2009072769A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP08857936A EP2229397A4 (fr) 2007-12-07 2008-11-24 Procédé de préparation de risédronate de sodium comme formes anhydres et hydratées
JP2010536837A JP2011506310A (ja) 2007-12-07 2008-11-24 無水及び水和物形態のリセドロン酸ナトリウムを製造する方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2007-0126592 2007-12-07
KR1020070126592A KR100925835B1 (ko) 2007-12-07 2007-12-07 리세드로네이트 나트륨 무수물 및 수화물의 제조방법

Publications (2)

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WO2009072769A2 true WO2009072769A2 (fr) 2009-06-11
WO2009072769A3 WO2009072769A3 (fr) 2009-08-27

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Country Status (4)

Country Link
EP (1) EP2229397A4 (fr)
JP (1) JP2011506310A (fr)
KR (1) KR100925835B1 (fr)
WO (1) WO2009072769A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8076483B2 (en) 2006-05-11 2011-12-13 M/S. Ind Swift Laboratories Limited Process for the preparation of pure risedronic acid or salts

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3279216A4 (fr) 2015-04-01 2019-06-19 Chugai Seiyaku Kabushiki Kaisha Procédé pour la production d'un hétéro-oligomère polypeptidique

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6410520B2 (en) * 2000-02-01 2002-06-25 The Procter & Gamble Company Selective crystallization of 3-pyridyl-1-hydroxyethylidene-1, 1-bisphosphonic acid sodium as the hemipentahydrate or monohydrate
PL372964A1 (en) * 2002-04-11 2005-08-08 Teva Pharmaceutical Indudstries, Ltd. Novel polymorphs and pseudopolymorphs of risedronate sodium
CZ293349B6 (cs) * 2002-10-25 2004-04-14 Léčiva, A.S. Nová krystalická forma sodné soli kyseliny 3-pyridyl-1-hydroxyethyliden-1,1-bisfosfonové
EP1775302A1 (fr) * 2005-10-11 2007-04-18 Sandoz A/S Méthode pour la préparation de risedronate de sodium cristallin
KR100961822B1 (ko) * 2006-09-28 2010-06-08 플레밍 레보레이토리스 리미티드 3-피리딜-1-히드록시에틸리딘-1,1-비스포스폰산 나트륨염의순수한 다형체 제조방법

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of EP2229397A4 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8076483B2 (en) 2006-05-11 2011-12-13 M/S. Ind Swift Laboratories Limited Process for the preparation of pure risedronic acid or salts

Also Published As

Publication number Publication date
WO2009072769A3 (fr) 2009-08-27
KR100925835B1 (ko) 2009-11-06
JP2011506310A (ja) 2011-03-03
KR20090059635A (ko) 2009-06-11
EP2229397A2 (fr) 2010-09-22
EP2229397A4 (fr) 2012-03-21

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