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WO2007132138A1 - Sels pharmaceutiquement acceptables et formes polymorphes - Google Patents

Sels pharmaceutiquement acceptables et formes polymorphes Download PDF

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Publication number
WO2007132138A1
WO2007132138A1 PCT/GB2007/000792 GB2007000792W WO2007132138A1 WO 2007132138 A1 WO2007132138 A1 WO 2007132138A1 GB 2007000792 W GB2007000792 W GB 2007000792W WO 2007132138 A1 WO2007132138 A1 WO 2007132138A1
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WO
WIPO (PCT)
Prior art keywords
tetra
sodium risedronate
sodium
alkali metal
risedronic
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/GB2007/000792
Other languages
English (en)
Inventor
Kreso Mihaljevic
Blazenko Bajic
Gordan Dinter
Ernest Mestrovic
Ana Kwokal
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.)
Pliva Hrvatska doo
Pliva Istrazivanje i Razvoj doo
Original Assignee
Pliva Hrvatska doo
Pliva Istrazivanje i Razvoj doo
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 Pliva Hrvatska doo, Pliva Istrazivanje i Razvoj doo filed Critical Pliva Hrvatska doo
Priority to EA200870525A priority Critical patent/EA200870525A1/ru
Priority to CA002649489A priority patent/CA2649489A1/fr
Priority to EP07712850A priority patent/EP2018392A1/fr
Publication of WO2007132138A1 publication Critical patent/WO2007132138A1/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
    • A61K31/66—Phosphorus compounds
    • A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
    • A61K31/663—Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • 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

Definitions

  • the present invention is concerned with new risedronate salts and new polymorphic forms thereof, processes of preparing the same, pharmaceutical compositions containing the same, therapeutic uses thereof and methods of treatment employing the same.
  • Risedronic acid is the international non-proprietary name of [l-hydroxy-2-(3- pyridinyl)ethylidene]bisphosphonic acid.
  • Risedronic acid has the following structural formula
  • a particularly preferred salt of risedronic acid is sodium risedronate.
  • Bisphosphonic acids such as risedronic acid, and pharmaceutically acceptable salts thereof, in particular sodium risedronate as referred to above, have been employed in the treatment of diseases of bone and calcium metabolism.
  • diseases include osteoporosis, hyperparathyroidism, hypercalcemia of malignancy, ostolytic bone metastases, myosistis ossifcans progressiva, calcinoisis universalis, arthritis, neuritis, bursitis, tendonitis and other inflammatory conditions.
  • Bisphosphonic acids tend to inhibit the resorption of bone tissue, which is beneficial to patients suffering from excessive bone loss.
  • all bisphosphonates do not exhibit the same degree of biological activity.
  • Some bisphosphonates have serious drawbacks with respect to the degree of toxicity in animals and the tolerability or negative side effects in humans.
  • the salt and hydrate forms of bisphosphonates alter both their solubility and their bioavailability.
  • EP 1243592B describes a process of preparing risedronic acid by reacting 3- pyridylacetic acid with phosphorous acid and phosphorous trichloride in a solvent.
  • the solvent is chlorobenzene
  • the reaction is carried out at a temperature in the range of 85- 100 0 C.
  • the solvent is fmorobenzene
  • the reaction is carried out at the reflux temperature of the reaction medium. Isolation of the risedronic acid involves separation thereof from the reaction mixture by treatment with alkali metal or ammonium hydroxide, bicarbonate or carbonate and subsequent treatment of the resulting alkali metal or ammonium risedronic acid salt with a strong mineral acid.
  • EP 04949844B also discloses a process of preparing bisphosphonic acids, but not risedronic acid.
  • Bisphosphonic acids, in particular alendronic acid, of the following general formula are prepared according to the process of EP 0494844B
  • n 2 to 8.
  • the process comprises melting a mixture of the corresponding aminocarboxylic acid and phosphorous acid obtained by heating at 90°C in the absence of an organic solvent, adding dropwise phosphorous trihalide under stirring and N 2 atmosphere, adding to the reaction mixture a hydrolyzing agent selected between water and a strong non-oxidizing acid and recovering the diphosphonic acid thus produced.
  • the process is described as being characterised in that the molar ratio between the aminocarboxylic acid, phosphorous acid and phosphorous trihalide in the reaction mixture is 1:3:2 and 1:20:6.
  • WO 01/57052 involves use of molten phosphorous acid, an amino carboxylic acid, phosphorous trihalide and a base in the bisphosphorylation step.
  • the base is employed to facilitate bisphosphorylation and can include organic and inorganic bases.
  • the more preferred bases are triethylamine, trimethylamine, potassium carbonate, pyridine and morpholine.
  • WO 05/063779 describes use of phosphorous oxychloride (POCI 3 ), instead of phosphorous trihalide. More specifically, WO 05/063779 describes reaction of a carboxylic acid with a mixture of phosphorous acid and phosphorous oxychloride, in the absence of solvents. Water, which is formed during bisphosphorylation, reacts with POCI 3 and consequently phosphoric acid (H 3 PO 4 ) is generated. The thus formed phosphoric acid can influence reaction conditions and can also form as an impurity in final product.
  • the scheme of the reaction is as follows
  • EP 1252170B describes a process for selectively producing sodium risedronate hemipentahydrate or monohydrate comprising the steps of (a) providing an aqueous solution of sodium risedronate, (b) heating the aqueous solution to a temperature from about 45 0 C to about 75 0 C, (c) adding a solvent to the aqueous solution, characterised in that the solvent is selected from the group consisting of alcohols, esters, ethers, ketones, amides and nitriles, and (d) optionally cooling the aqueous solution.
  • WO 04/037252 discloses crystalline hydrated forms of sodium risedronate, which contain from 6.4 up to 22 weight % of sodium based on the anhydrous substance, and in the case where the sodium content is lower than 7.5 weight %, then 15 to 23 weight % of crystalline water is present, or in the case where the sodium content is higher than 7.5 weight %, then 4.5 to 18 weight % of crystalline water is present.
  • the pentahydrate of the monosodium salt which contains from 5.5 to 7.5 weight % of sodium and 20 to 23 weight % of crystalline water
  • the trihydrate of the trisodium salt which contains from 19 to 21 weight % of sodium and 12 to 14 weight % of crystalline water
  • the monohydrate of the disodium salt which contains from 13 to 15 weight % of sodium and 4.5 to 6.5 weight % of crystalline water.
  • WO 03/086355 describes polymorph forms B, Bl 5 BB, C, D, E, F 5 G and H of sodium risedronate and processes of preparing these various polymorphs.
  • Pharmaceutically acceptable alkali metal salts include sodium and potassium salts. Specifically, there is provided by the present invention terra-sodium risedronate.
  • the present invention also provides tetra-sodium risedronate as tetra-sodium risedronate Form I, tetra-sodium risedronate Form II and tetra-sodium risedronate Form III.
  • Tetra-sodium risedronate Form I as provided by the present invention can be characterised as having an X-ray powder diffraction pattern, or substantially the same X-ray powder diffraction pattern, as shown in Figure 1.
  • Tetra-sodium risedronate Form I is further characterised as having characteristic peaks (2 ⁇ ): 6.33, 9.76, 11.05, 12.15, 12.65, 15.13, 16.77, 17.0, 18.99, 22.23, 22.61 and 30.53°.
  • Tetra-sodium risedronate Form I is further characterised as having an FTIR transmission spectrum, or substantially the same FTIR transmission spectrum, as shown in Figure 2.
  • Tetra-sodium risedronate Form I is further characterised as having an FTNIR reflection spectrum, or substantially the same FTNIR reflection spectrum, as shown in Figure 3.
  • Tetra-sodium risedronate Form I can be still further characterised by a typical DSC thermograph as shown in Figure 4.
  • Tetra-sodium risedronate Form I has a DSC endotherm temperature onset of about 175°C.
  • Tetra-sodium risedronate Form II as provided by the present invention can be characterised as having an X-ray powder diffraction pattern, or substantially the same X-ray powder diffraction pattern, as shown in Figure 5.
  • Tetra-sodium risedronate Form II is further characterised as having characteristic peaks (2 ⁇ ): 4.33, 5.03, 5.48, 6.94, 9.94, 11.06, 11.89, 12.94, 13.16, 14.14, 16.63, 21.38 and 22.20°.
  • Tetra-sodium risedronate Form II is further characterised as having an FTIR transmission spectrum, or substantially the same FTIR transmission spectrum, as shown in Figure 6.
  • Tetra-sodium risedronate Form II according to the present invention is further characterised as having an FTNIR reflection spectrum, or substantially the same FTNIR reflection spectrum, as shown in Figure 7.
  • Tetra-sodium risedronate Form II can be still further characterised by a typical DSC thermograph as shown in Figure 8. Tetra-sodium risedronate Form II has a DSC endotherm temperature onset of about 120°C.
  • Tetra-sodium risedronate Form III as provided by the present invention can be characterised as having an X-ray powder diffraction pattern, or substantially the same X-ray powder diffraction pattern, as shown in Figure 9.
  • Tetra-sodium risedronate Form III according to the present invention is further characterised as having characteristic peaks (2 ⁇ ): 5.17, 5.57 and 7.06°.
  • Tetra-sodium risedronate Form III according to the present invention is further characterised as having an FTIR transmission spectrum, or substantially the same FTIR transmission spectrum, as shown in Figure 10.
  • Tetra-sodium risedronate Form III according to the present invention is further characterised as having an FTNIR reflection spectrum, or substantially the same FTNIR reflection spectrum, as shown in Figure 11.
  • Tetra-sodium risedronate Form III can be still further characterised by a typical DSC thermograph as shown in Figure 12. Tetra-sodium risedronate Form III has a DSC endotherm temperature onset of about 80°C.
  • the present invention also provides a process of preparing a tetra-(alkali metal) salt of risedronic acid according to the present invention substantially as hereinbefore described, which comprises contacting risedronic free acid with a source of a pharmaceutically acceptable alkali metal and thus converting the free acid to a tetra- (alkali metal) salt of risedronic acid. More particularly, a process according to the present invention comprises contacting a suspension of risedronic free acid with a source of a pharmaceutically acceptable alkali metal, adjusting the pH to about 13 to 14, preferably about 13.4, and thereby converting the risedronic free acid to a tetra- (alkali metal) salt of risedronic acid according to the present invention substantially as hereinbefore described.
  • the source of the pharmaceutically acceptable alkali metal is the corresponding alkali metal hydroxide, preferably sodium hydroxide, whereby addition of the hydroxide achieves adjustment to the above referred to pH range of 13 to 14.
  • the reaction scheme can be illustrated as follows.
  • a process as described herein prepares tetra-sodium risedronate as any one of Forms I, II or III as described herein.
  • a suspension of risedronic free acid and water is maintained at about 2O 0 C, followed by the addition of sodium hydroxide to form a solution.
  • the pH is adjusted to about 13.4.
  • a C 1-4 alcohol such as methanol or ethanol, is added at a temperature of up to about 3O 0 C, followed by crystallization of tetra-sodium risedronate Form I according to the present invention.
  • a suspension of risedronic free acid and water is maintained at about 2O 0 C, followed by the addition of sodium hydroxide to form a solution.
  • the pH is adjusted to about 13.4.
  • the solution is heated to reflux and preferably a C 1-4 alcohol, such as methanol or ethanol, is added under reflux. Crystallization of tetra-sodium risedronate starts under reflux followed by cooling and filtration to obtain tetra-sodium risedronate Form II according to the present invention.
  • a suspension of risedronic free acid and water is maintained at about 2O 0 C, followed by the addition of sodium hydroxide to form a solution.
  • the pH is adjusted to about 13.4.
  • the solution is heated to reflux and preferably a C 1 ⁇ alcohol, such as methanol or ethanol, is added under reflux. Crystallization of tetra-sodium risedronate starts under reflux followed by cooling, further addition of a C 1-4 alcohol and filtration to obtain tetra- sodium risedronate Form III according to the present invention.
  • risedronic acid as employed in the above reactions is prepared by the reaction of phosphorous acid with pyridylacetic acid, optionally present as a hydrohalide salt.
  • the reaction is also carried out in the presence of phosphorous trihalide and phosphorous acid is formed in situ in the reaction mixture by the reaction of phosphorous trihalide and water. This can be represented by the following reaction scheme. (1) PX 3 (excess) + H 2 O
  • pyridylacetic acid is employed in the form of the hydrochloride salt and the phosphorous trihalide employed is phosphorous trichloride.
  • a tetra-(alkali metal) salt of risedronic acid as provided by the present invention has therapeutic utility in the treatment of diseases associated with bone resorption disorders and more specifically in the treatment of diseases of bone and calcium metabolism.
  • diseases include osteoporosis, hyperparathyroidism, hypercalcemia of malignancy, ostolytic bone metastases, myosistis ossifcans progressiva, calcinoisis universalis, arthritis, neuritis, bursitis, tendonitis and other inflammatory conditions.
  • the present invention further provides, therefore, a pharmaceutical composition
  • a pharmaceutical composition comprising a therapeutically effective dose of a tetra-(alkali metal) salt of risedronic acid, together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
  • Excipients are chosen according to the pharmaceutical form and the desired mode of administration.
  • therapeutically effective amount means an amount a tetra- (alkali metal) salt of risedronic acid as prepared by the present invention, which is capable of preventing, ameliorating or eliminating a bone resorption disorder.
  • pharmaceutically acceptable it is meant that the carrier, diluent or excipient is compatible with a tetra-(alkali metal) salt of risedronic acid as prepared by the present invention and is not deleterious to a recipient thereof.
  • a tetra-(alkali metal) salt of risedronic acid is administered to animals and humans in unit forms of administration, mixed with conventional pharmaceutical carriers, for the prophylaxis or treatment of the above disorders or diseases.
  • the appropriate unit forms of administration include forms for oral administration, such as tablets, gelatin capsules, powders, granules and solutions or suspensions to be taken orally, forms for sublingual, buccal, intratracheal or intranasal administration, forms for subcutaneous, intramuscular or intravenous administration and forms for rectal administration.
  • a tetra- (alkali metal) salt of risedronic acid can be used in creams, ointments or lotions.
  • the dose of a tetra-(alkali metal) salt of risedronic acid can vary between about 0.01 and about 50 mg per kg of body weight per day.
  • Each unit dose can contain from about 0.1 to about 1000 mg, preferably about 1 to about 500 mg, of a tetra-(alkali metal) salt of risedronic acid, in combination with a pharmaceutical carrier.
  • This unit dose can be administered 1 to 5 times a day so as to administer a daily dosage of about 0.5 to about 5000 mg, preferably about 1 to about 2500 mg.
  • a tetra-(alkali metal) salt of risedronic acid is mixed with a pharmaceutical vehicle such as gelatin, starch, lactose, magnesium stearate, talc, gum arabic or the like.
  • a pharmaceutical vehicle such as gelatin, starch, lactose, magnesium stearate, talc, gum arabic or the like.
  • the tablets can be coated with sucrose, a cellulose derivative or other appropriate substances, or else they can be treated so as to have a prolonged or delayed activity and so as to release a predetermined amount of active principle continuously.
  • the use of tablets is generally preferred for administration of a tetra-(alkali metal) salt of risedronic acid as provided by the present invention.
  • a preparation in the form of gelatin capsules can be obtained by mixing a tetra-(alkali metal) salt of risedronic acid with a diluent and pouring the resulting mixture into soft or hard gelatin capsules.
  • a preparation in the form of a syrup or elixir or for administration in the form of drops can contain a tetra-(alkali metal) salt of risedronic acid, typically in conjunction with a sweetener, which is preferably calorie-free, optionally antiseptics such as methylparaben and propylparaben, as well as a flavoring and an appropriate color.
  • a sweetener which is preferably calorie-free
  • optionally antiseptics such as methylparaben and propylparaben, as well as a flavoring and an appropriate color.
  • Water-dispersible granules or powders can contain a tetra-(alkali metal) salt of risedronic acid mixed with dispersants or wetting agents, or suspending agents such as polyvinylpyrrolidone, as well as with sweeteners or taste correctors.
  • Rectal administration is effected using suppositories prepared with binders which melt at the rectal temperature, for example polyethylene glycols.
  • Parenteral administration is effected using aqueous suspensions, isotonic saline solutions or sterile and injectable solutions which contain pharmacologically compatible dispersants and/or wetting agents, for example propylene glycol or butylene glycol.
  • a tetra-(alkali metal) salt of risedronic acid can also be formulated as microcapsules, with one or more carriers or additives if appropriate.
  • tetra-(alkali metal) salt of risedronic acid for use in therapy.
  • the present invention further provides a tetra-(alkali metal) salt of risedronic acid, for use in the manufacture of a medicament for the treatment of a disease state prevented, ameliorated or eliminated by the administration of an inhibitor of bone resorption. More specifically, the present invention provides a tetra-(alkali metal) salt of risedronic acid, for use in the manufacture of a medicament for the treatment of diseases of bone and calcium metabolism, and even more specifically for the treatment of any one of the following: osteoporosis, hyperparathyroidism, hypercalcemia of malignancy, ostolytic bone metastases, myosistis ossifcans progressiva, calcinoisis universalis, arthritis, neuritis, bursitis, tendonitis and other inflammatory conditions.
  • the present invention also provides a method of treating a disease state prevented, ameliorated or eliminated by the administration of an inhibitor of bone resorption in a patient in need of such treatment, which method comprises administering to the patient a therapeutically effective amount of a tetra-(alkali metal) salt of risedronic acid.
  • the present invention provides a method of treating diseases of bone and calcium metabolism, such as osteoporosis, hyperparathyroidism, hypercalcemia of malignancy, ostolytic bone metastases, myosistis ossifcans progressiva, calcinoisis universalis, arthritis, neuritis, bursitis, tendonitis and other inflammatory conditions, in a patient in need of such treatment, which method comprises administering to the patient a therapeutically effective amount of a tetra- (alkali metal) salt of risedronic acid.
  • diseases of bone and calcium metabolism such as osteoporosis, hyperparathyroidism, hypercalcemia of malignancy, ostolytic bone metastases, myosistis ossifcans progressiva, calcinoisis universalis, arthritis, neuritis, bursitis, tendonitis and other inflammatory conditions.
  • Figure 1 is an XRPD pattern of tetra-sodium risedronate Form I according to the present invention.
  • Figure 2 is an FTIR transmission spectrum of tetra-sodium risedronate Form I according to the present invention recorded by KBr disc and resolution 4 cm "1 .
  • Figure 3 is an FTNIR reflection spectrum of tetra-sodium risedronate Form I according to the present invention, recorded with solid probe accessories and resolution 8 cm “1 .
  • Figure 4 is a DSC thermogram of tetra-sodium risedronate Form I according to the present invention, recorded at a heat rate of 10°C/min (endotherm temperature onset is at 175 0 C ).
  • Figure 5 is an XRPD pattern of tetra-sodium risedronate Form II according to the present invention.
  • Figure 6 is an FTIR transmission spectrum of tetra-sodium risedronate Form II according to the present invention recorded by KBr disc and resolution 4 cm “1 .
  • Figure 7 is an FTNIR reflection spectrum of tetra-sodium risedronate Form II according to the present invention, recorded with solid probe accessories and resolution 8 cm “1 .
  • Figure 8 is a DSC thermogram of tetra-sodium risedronate Form II according to the present invention, recorded at a heat rate of 10°C/min (endotherm temperature onset is at 12O 0 C ).
  • Figure 9 is an XRPD pattern of tetra-sodium risedronate Form III according to the present invention.
  • Figure 10 is an FTIR transmission spectrum of tetra-sodium risedronate Form III according to the present invention recorded by KBr disc and resolution 4 cm “1 .
  • Figure 11 is an FTNIR reflection spectrum of tetra-sodium risedronate Form III according to the present invention, recorded with solid probe accessories and resolution 8 cm “1 .
  • Figure 12 is a DSC thermogram of tetra-sodium risedronate Form III according to the present invention, recorded at a heat rate of 10°C/min (endotherm temperature onset is at 8O 0 C ).
  • the above referenced FTIR transmission spectra for each of polymorphs I, II and III were obtained by using Perkin Elmer Spectrum GX FT-IR Spectrometer (Detector: DTGS, Beam splitter: extended KBr, Spectral Range: 4000-400Cm "1 , Resolution: 4cm " ⁇ 4 scans, Samples prepared as KBr pellets).
  • the above referenced FTNIR reflection spectra for each of polymorphs I 5 II and III were obtained by using Bruker NIR Multi Purpose Analyser (MPA). (The spectra were recorded in a diffuse reflectance mode using integrating sphere for collecting reflecting beams.
  • the measurements were carried out over the range 4000 cm “1 - 12000 cm “1 , with a resolution of 8 cm “1 .
  • the spectra were averaged over 32 scans.
  • the system was governed via the software OPUS that includes routines for acquisition and processing of spectra).
  • risedronate tetra-sodium salt 21.17 g, was obtained after filtration, washed with 100ml of a water / methanol solution (1 / 4) and dried. Analysis carried out confirmed the risedronate tetra-sodium salt thus prepared to be tetra-sodium risedronate form I.
  • risedronate tetra-sodium salt 19.58 g, was obtained after filtration, washed with 100ml of a water / methanol cold solution (1 / 4) and dried. Analysis carried out confirmed the risedronate tetra-sodium salt thus prepared to be tetra-sodium risedronate form II.

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Abstract

La présente invention concerne de nouveaux sels risedronates et de nouvelles formes polymorphes de ceux-ci, notamment un sel pharmaceutiquement acceptable de tétra-(métal alcalin) de l'acide risedronique et de nouvelles formes polymorphes de celui-ci, des procédés permettant de les préparer, des compositions pharmaceutiques les contenant, leurs utilisations thérapeutiques et des procédés de traitement les employant.
PCT/GB2007/000792 2006-05-12 2007-03-06 Sels pharmaceutiquement acceptables et formes polymorphes Ceased WO2007132138A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EA200870525A EA200870525A1 (ru) 2006-05-12 2007-03-06 Фармацевтически приемлемые соли и полиморфные формы
CA002649489A CA2649489A1 (fr) 2006-05-12 2007-03-06 Sels pharmaceutiquement acceptables et formes polymorphes
EP07712850A EP2018392A1 (fr) 2006-05-12 2007-03-06 Sels pharmaceutiquement acceptables et formes polymorphes

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0609465.0 2006-05-12
GBGB0609465.0A GB0609465D0 (en) 2006-05-12 2006-05-12 Pharmaceutically acceptable salts and polymorphic forms

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WO2007132138A1 true WO2007132138A1 (fr) 2007-11-22

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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

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004037252A1 (fr) * 2002-10-25 2004-05-06 Zentiva, A.S. Nouvelle forme cristalline de sel de sodium d'acide 3-pyridyl-1-hydroxyethylidene-1,1-biphosphonique

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004037252A1 (fr) * 2002-10-25 2004-05-06 Zentiva, A.S. Nouvelle forme cristalline de sel de sodium d'acide 3-pyridyl-1-hydroxyethylidene-1,1-biphosphonique

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

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CA2649489A1 (fr) 2007-11-22
EP2018392A1 (fr) 2009-01-28
EA200870525A1 (ru) 2009-04-28
GB0609465D0 (en) 2006-06-21

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