WO2009092993A1 - Nouveau sel de tégasérod - Google Patents

Nouveau sel de tégasérod Download PDF

Info

Publication number
WO2009092993A1
WO2009092993A1 PCT/GB2008/051123 GB2008051123W WO2009092993A1 WO 2009092993 A1 WO2009092993 A1 WO 2009092993A1 GB 2008051123 W GB2008051123 W GB 2008051123W WO 2009092993 A1 WO2009092993 A1 WO 2009092993A1
Authority
WO
WIPO (PCT)
Prior art keywords
tegaserod
pimelate
gastrointestinal disorder
composition
bowel syndrome
Prior art date
Application number
PCT/GB2008/051123
Other languages
English (en)
Inventor
Abhay Gaitonde
Bindu Manojkumar
Sunanda Phadtare
Sinderpal Tank
Bharati Choudhari
Original Assignee
Generics [Uk] Limited
Mylan Development Centre Private Limited
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 Generics [Uk] Limited, Mylan Development Centre Private Limited filed Critical Generics [Uk] Limited
Publication of WO2009092993A1 publication Critical patent/WO2009092993A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system

Definitions

  • the present invention relates to a novel salt of tegaserod, namely tegaserod pimelate, and to processes for the preparation thereof.
  • the invention also relates to crystalline forms of the novel salt and to pharmaceutical compositions comprising the novel salt. Further, the invention relates to uses of said compositions to provide methods of treating patients suffering from gastrointestinal disorders.
  • Tegaserod chemically named 2-[(5-methoxy-li ⁇ -indol-3-yl)methylene]-IV-pentylhydrazine- carboximidamide, is a selective serotonin 4 (5-HT 4 ) receptor agonist, which can be used to treat gastrointestinal disorders such as heartburn, bloating, postoperative ileus, abdominal pain and discomfort, epigastric pain, nausea, vomiting, regurgitation, intestinal pseudoobstruction, irritable bowel syndrome and gastro-oesophageal reflux.
  • Tegaserod as the maleate salt, is marketed for the short-term treatment of irritable bowel syndrome in women whose primary bowel symptom is constipation.
  • Tegaserod represented by formula (I), was first described in US 5 510 353. Also described is the maleate salt, but interestingly a method of manufacturing tegaserod maleate is not disclosed. The only characterising data is the melting point which is disclosed as 190 0 C for the maleate salt and 124°C for the tegaserod base.
  • WO 2006/116953 describes crystalline forms of the hydrobromide, f ⁇ marate and oxalate salts of tegaserod. Also claimed is a process for preparing the hydrochloride, hydrobromide, fumarate, tartrate, citrate, lactate, mesylate, oxalate, succinate, glutarate, adipate, salicylate, sulphate, mandelate, camphor sulphonate and hydrogen sulphate salts of tegaserod from a specific crystalline form of tegaserod base.
  • Another process described is a method of preparing the fumarate, maleate, tartrate, citrate, mesylate, lactate, succinate, oxalate, hydrochloride, salicylate, glutarate, adipate, hydrobromide, sulphate and hydrogen sulphate from a hydrogen halide salt of tegaserod.
  • API active pharmaceutical ingredient
  • the rate of dissolution of an API that has poor aqueous solubility is often problematic.
  • the aqueous solubility is a major influence on the bioavailability of the API such that a poorly soluble API can mean the API is not available to have a pharmaceutical effect on the body.
  • the API can also cause problems during manufacture of a pharmaceutical composition. For example, flowability, compactability and stickiness are all factors affected by the solid state properties of an API.
  • the present invention provides a novel salt of tegaserod, namely tegaserod pimelate, as well as a crystalline form of said salt.
  • polymorphism influences every aspect of the solid state properties of an API and one of the important aspects of polymorphism in pharmaceuticals is the possibility of interconversion from one crystalline form to another. It is important that stable crystalline forms are used in pharmaceutical compositions as, for example, conversion from a form showing greater aqueous dissolution and potentially better bioavailability to a less soluble form can potentially have disastrous consequences.
  • a first aspect according to the invention provides the compound tegaserod pimelate or tautomeric form thereof and/or a pharmaceutically acceptable solvate or hydrate thereof.
  • the tegaserod pimelate may exist in one or more polymorphic, tautomeric, hydrate and/or solvate forms.
  • the present invention embraces all polymorphic forms and their mixtures, all tautomeric forms and their mixtures, all hydrate forms and their mixtures, and all solvate forms and their mixtures.
  • tegaserod is defined for convenience by reference to one guanidino form only, the invention is not to be understood as being in any way limited by the particular nomenclature or graphic representation employed. - A -
  • a novel crystalline form of tegaserod pimelate is provided with a characteristic XRD spectrum having two or more peaks (preferably three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, fifteen or more, twenty or more, or twenty-two peaks) with 2 ⁇ values at 8.14, 11.23, 13.10, 13.60, 13.82, 15.24, 15.61, 15.89, 16.26, 17.82, 18.14, 18.52, 19.24, 19.77, 20.59, 21.17, 22.16, 22.50, 23.93, 24.78, 25.43, 28.85 ⁇ 0.2 °2 ⁇ .
  • tegaserod pimelate is provided with a characteristic XRD spectrum having peaks with 2 ⁇ values at 8.14, 11.23, 13.10, 13.60, 13.82, 15.24, 15.61, 15.89, 16.26, 17.82, 18.14, 18.52, 19.24, 19.77, 20.59, 21.17, 22.16, 22.50, 23.93, 24.78, 25.43, 28.85 ⁇ 0.2 °2 ⁇ .
  • the tegaserod pimelate has an XRPD trace substantially as shown in figure 1.
  • a crystalline form of tegaserod pimelate characterised by a DSC with an endothermic peak at about 229.8°C ⁇ 0.5 0 C, preferably at about 229.78°C ⁇ 0.5 0 C.
  • the tegaserod pimelate has a DSC trace substantially as shown in figure 2.
  • the tegaserod pimelate may have a TGA trace substantially as shown in figure 3.
  • the tegaserod pimelate according to the above described aspects and embodiments has a chemical purity of greater than 95%, 96%, 97%, 98% or 99% (as measured by HPLC).
  • the tegaserod pimelate according to the above described aspects and embodiments has a polymorphic purity of greater than 95%, 96%, 97%, 98% or 99% (as measured by XRPD or DSC).
  • a fourth aspect provides a process for the preparation of tegaserod pimelate according to the invention, preferably crystalline tegaserod pimelate, comprising the steps of: (a) mixing tegaserod and pimelic acid in a solvent; and (b) isolating the resultant salt.
  • the pimelic acid is added as a solution of the free acid, preferably the solvent of the pimelic acid solution is an aqueous solvent, most preferably the aqueous solvent is water.
  • the salt is isolated by filtration, preferably by vacuum filtration.
  • the tegaserod pimelate is obtained on an industrial scale, preferably in batches of 0.5kg, lkg, 5kg, 10kg, 50kg, 100kg, 500kg or more.
  • a fifth aspect according to the invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising tegaserod pimelate according to the invention or prepared according to the invention and one or more pharmaceutically acceptable excipients.
  • the composition is a solid composition, most preferably a tablet or capsule composition.
  • a sixth aspect provides a composition according to the invention for use in the treatment or prevention of a gastrointestinal disorder, preferably selected from the list comprising heartburn, bloating, postoperative ileus, abdominal pain and discomfort, epigastric pain, nausea, vomiting, regurgitation, intestinal pseudo-obstruction, irritable bowel syndrome and gastro-oesophageal reflux.
  • a gastrointestinal disorder preferably selected from the list comprising heartburn, bloating, postoperative ileus, abdominal pain and discomfort, epigastric pain, nausea, vomiting, regurgitation, intestinal pseudo-obstruction, irritable bowel syndrome and gastro-oesophageal reflux.
  • a gastrointestinal disorder preferably selected from the list comprising heartburn, bloating, postoperative ileus, abdominal pain and discomfort, epigastric pain, nausea, vomiting, regurgitation, intestinal pseudo-obstruction, irritable bowel syndrome and gastro-oesophageal reflux.
  • the gastrointestinal disorder is irritable bowel syndrome.
  • tegaserod pimelate according to any of the aspects or embodiments described above for use as a medicament.
  • An eighth aspect provides tegaserod pimelate according to the invention for use in the treatment or prevention of a gastrointestinal disorder.
  • the gastrointestinal disorder is selected from the group comprising heartburn, bloating, postoperative ileus, abdominal pain and discomfort, epigastric pain, nausea, vomiting, regurgitation, intestinal pseudo-obstruction, irritable bowel syndrome and gastro- oesophageal reflux, most preferably the disorder is irritable bowel syndrome.
  • a method of treating or preventing a gastrointestinal disorder preferably selected from the group comprising heartburn, bloating, postoperative ileus, abdominal pain and discomfort, epigastric pain, nausea, vomiting, regurgitation, intestinal pseudo-obstruction, irritable bowel syndrome and gastro-oesophageal reflux (preferably irritable bowel syndrome), comprising administering to a patient in need thereof a composition comprising a pharmaceutically or prophylactically effective amount of tegaserod pimelate according to any of the aspects or embodiments described above.
  • the patient is a mammal, preferably a human.
  • a tenth aspect provides the use of tegaserod pimelate according to any of the aspects or embodiments described above in the manufacture of a medicament for use in the treatment or prevention of a gastrointestinal disorder.
  • the gastrointestinal disorder is selected from the group comprising heartburn, bloating, postoperative ileus, abdominal pain and discomfort, epigastric pain, nausea, vomiting, regurgitation, intestinal pseudo-obstruction, irritable bowel syndrome and gastro-oesophageal reflux, preferably irritable bowel syndrome.
  • Figure 1 shows the XRPD of tegaserod pimelate.
  • Figure 2 shows the DSC of tegaserod pimelate.
  • Figure 3 shows the TGA of tegaserod pimelate.
  • crystalline form As used herein the terms "crystalline form”, “polymorph” and “polymorphic form” are used interchangeably.
  • XRD X-ray powder diffraction trace, spectrum or pattern.
  • the present invention provides the novel pimelate salt of tegaserod and a process for its preparation.
  • the process disclosed is simple and amenable to scale up and is capable of providing the salt in consistent crystalline and chemical purity of greater than 95% respectively, preferably greater than 96%, more preferably greater than 97%. Particularly preferred is a purity of greater than 98% and most preferred is a purity of greater than 99% irrespective of the scale of preparation.
  • a preferred process according to the invention for preparing tegaserod pirn elate according to the invention comprises mixing tegaserod and pimelic acid.
  • the pimelic acid is dissolved in a solvent.
  • the solvent is an aqueous solvent, most preferably water.
  • the tegaserod is in the form of the free base.
  • the tegaserod can be completely or only partially dissolved in one or a mixture of solvent(s) and the process still falls within the scope of the invention, and further that the tegaserod, pimelic acid and solvent can be combined in any order and the process remains within the scope of the invention.
  • certain embodiments according to the invention comprise adding tegaserod to the solvent(s), to which is added the pimelic acid, preferably in solution. Whatever their nature the pimelic acid solution and the tegaserod solution should be miscible to create a single phase.
  • the solvent in which the tegaserod is dissolved should be miscible with the aqueous pimelic acid solution.
  • C 1 -C 6 alcohols are advantageous, preferably selected from the group comprising methanol, ethanol, isopropyl alcohol (IPA), tert-butanol and isobutanol, more preferably methanol, but other polar organic solvents, especially polar protic organic solvents, capable of dissolving tegaserod can be utilised.
  • the resulting reaction mixture comprising the tegaserod and the pimelic acid in certain embodiments can be stirred to increase the precipitation of the solid salt. It is preferred that the stirring occurs at between about 20-30 0 C or approximately room temperature, but it is envisaged that the stirring conditions may be varied and still remain within the scope of the invention. Preferably the reaction mixture comprising the tegaserod and the pimelic acid is stirred for between about 0.5-3 hours.
  • the solid product obtained can then be isolated by any means common in the field or known to the skilled artisan.
  • the solid salt is obtained by evaporation of the solvent.
  • the solid product is filtered.
  • the product is dried at a temperature that does not induce conversion of the crystalline form obtained or cause the salt or crystalline form to degrade. The inventors have found that drying the product at about 35-40 0 C is advantageous.
  • the solid product is dried under vacuum until a constant weight is obtained.
  • the tegaserod pimelate according to the invention may also be further purified if required.
  • the inventors have found that dissolving the tegaserod pimelate in an organic solvent and then causing the salt to precipitate from the solution results in particularly pure tegaserod pimelate.
  • the organic solvent is a protic or aprotic solvent, preferably ethyl acetate.
  • the mixture is heated to facilitate dissolution of the tegaserod pimelate, in certain embodiments to between about 40-90 0 C, most preferably to between about 70-80 0 C, when the solvent is ethyl acetate.
  • the mixture may then be cooled to precipitate the tegaserod pimelate or in alternative embodiments an anti-solvent may be added.
  • the mixture is cooled to between about 20-30 0 C.
  • the resultant precipitated solid can be isolated by any means, preferably by vacuum filtration.
  • the solid obtained may then be washed, preferably with ethyl acetate, and is preferably dried, preferably at about 40 0 C, preferably until a constant weight is achieved.
  • tegaserod pimelate as described above and further crystallisation from solvents such as ethyl acetate result in tegaserod pimelate having both chemical and crystalline purity of greater than 99%.
  • Illustrative of the invention is a pharmaceutical composition comprising tegaserod pimelate and one or more pharmaceutical excipients.
  • a process for preparing the composition comprising mixing tegaserod pimelate according to the invention and a pharmaceutically acceptable excipient.
  • a yet further aspect of the invention provides treatment of a 5-HT 4 receptor mediated disorder in a subject in need thereof comprising administering to the subject a composition comprising a therapeutically effective amount of tegaserod pimelate.
  • 5-HT 4 receptor mediated disorders comprise gastrointestinal disorders such as heartburn, bloating, postoperative ileus, abdominal pain and discomfort, epigastric pain, nausea, vomiting, regurgitation, intestinal pseudo-obstruction, irritable bowel syndrome and gastro-oesophageal reflux.
  • tegaserod pimelate for treating a 5-HT 4 receptor mediated disorder in a subject in need thereof.
  • the tegaserod pimelate may be in amorphous form or any of a number of crystalline forms.
  • the pharmaceutical compositions of the present invention may contain one or more excipients. Excipients are added to the composition for a variety of purposes. Diluents increase the bulk of a solid pharmaceutical composition, and may make a pharmaceutical dosage form containing the composition easier for the patient and care giver to handle. Diluents for solid compositions include, for example, microcrystalline cellulose (e.g.
  • Avicel ® microfine cellulose, lactose, starch, pregelatinized starch, calcium carbonate, calcium sulphate, sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, kaolin, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, polymethacrylates (e.g. Eudragit ® ), potassium chloride, powdered cellulose, sodium chloride, sorbitol and talc.
  • Solid pharmaceutical compositions that are compacted into a dosage form, such as a tablet may include excipients whose functions include helping to bind the active ingredient and other excipients together after compression.
  • Binders for solid pharmaceutical compositions include acacia, alginic acid, carbomer (e.g. Carbopol ), carboxymethyl cellulose sodium, dextrin, ethyl cellulose, gelatin, guar gum, hydrogenated vegetable oil, hydroxyethyl cellulose, hydroxypropyl cellulose (e.g. Klucel ® ), hydroxypropyl methyl cellulose (e.g.
  • Methocel liquid glucose, magnesium aluminium silicate, maltodextrin, methyl cellulose, polymethacrylates, povidone (e.g. Kollidon ® , Plasdone ® ), pregelatinized starch, sodium alginate and starch.
  • povidone e.g. Kollidon ® , Plasdone ®
  • the dissolution rate of a compacted solid pharmaceutical composition in the patient's stomach may be increased by the addition of a disintegrant to the composition.
  • Disintegrants include alginic acid, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium (e.g. Ac-Di-SoI , Primellose ), colloidal silicon dioxide, croscarmellose sodium, crospovidone (e.g. Kollidon ® , Polyplasdone ® ), guar gum, magnesium aluminium silicate, methyl cellulose, microcrystalline cellulose, polacrilin potassium, powdered cellulose, pregelatinized starch, sodium alginate, sodium starch glycolate (e.g. Explotab ) and starch.
  • alginic acid include alginic acid, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium (e.g. Ac-Di-SoI , Primellose ), colloidal silicon dioxide, croscarmellose sodium, crospovidone (e.g. Kollid
  • Glidants can be added to improve the flowability of a non-compacted solid composition and to improve the accuracy of dosing.
  • Excipients that may function as glidants include colloidal silicon dioxide, magnesium trisilicate, powdered cellulose, starch, talc and tribasic calcium phosphate.
  • a dosage form such as a tablet is made by the compaction of a powdered composition
  • the composition is subjected to pressure from a punch and dye.
  • Some excipients and active ingredients have a tendency to adhere to the surfaces of the punch and dye, which can cause the product to have pitting and other surface irregularities.
  • a lubricant can be added to the composition to reduce adhesion and ease the release of the product from the dye.
  • Lubricants include magnesium stearate, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulphate, sodium stearyl fumarate, stearic acid, talc and zinc stearate.
  • flavouring agents and flavour enhancers make the dosage form more palatable to the patient.
  • Common flavouring agents and flavour enhancers for pharmaceutical products include maltol, vanillin, ethyl vanillin, menthol, citric acid, fumaric acid, ethyl maltol and tartaric acid.
  • Solid and liquid compositions may also be dyed using any pharmaceutically acceptable colorant to improve their appearance and/or facilitate patient identification of the product and unit dosage level.
  • liquid pharmaceutical compositions of the present invention the tegaserod salt and any other solid excipients are dissolved or suspended in a liquid carrier such as water, vegetable oil, alcohol, polyethylene glycol, propylene glycol or glycerine.
  • a liquid carrier such as water, vegetable oil, alcohol, polyethylene glycol, propylene glycol or glycerine.
  • Liquid pharmaceutical compositions may further contain emulsifying agents to disperse uniformly throughout the composition an active ingredient or other excipient that is not soluble in the liquid carrier.
  • Emulsifying agents that may be useful in liquid compositions of the present invention include, for example, gelatin, egg yolk, casein, cholesterol, acacia, tragacanth, chondrus, pectin, methyl cellulose, carbomer, cetostearyl alcohol and cetyl alcohol.
  • Liquid pharmaceutical compositions of the present invention may also contain a viscosity enhancing agent to improve the mouth-feel or organoleptic qualities of the product and/or coat the lining of the gastrointestinal tract.
  • a viscosity enhancing agent include acacia, alginic acid, bentonite, carbomer, carboxymethyl cellulose calcium or sodium, cetostearyl alcohol, methyl cellulose, ethyl cellulose, gelatin, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, maltodextrin, polyvinyl alcohol, povidone, propylene carbonate, propylene glycol alginate, sodium alginate, sodium starch glycolate, starch tragacanth and xanthan gum.
  • Sweetening agents such as sorbitol, saccharin, sodium saccharin, sucrose, aspartame, fructose, mannitol and invert sugar may be added to improve the taste.
  • Preservatives and chelating agents such as alcohol, sodium benzoate, butylated hydroxytoluene, butylated hydroxyanisole and ethylenediaminetetraacetic acid may be added at levels safe for ingestion to improve storage stability.
  • a liquid composition may also contain a buffer such as gluconic acid, lactic acid, citric acid or acetic acid, sodium gluconate, sodium lactate, sodium citrate or sodium acetate.
  • a buffer such as gluconic acid, lactic acid, citric acid or acetic acid, sodium gluconate, sodium lactate, sodium citrate or sodium acetate.
  • the solid compositions of the present invention include powders, granulates, aggregates and compacted compositions.
  • the dosages include dosages suitable for oral, buccal, rectal, parenteral (including subcutaneous, intramuscular, and intravenous), inhalant and ophthalmic administration. Although the most suitable administration in any given case will depend on the nature and severity of the condition being treated, the most preferred route of the present invention is oral.
  • the dosages may be conveniently presented in unit dosage form and prepared by any of the methods well-known in the pharmaceutical arts. Dosage forms include solid dosage forms like tablets, powders, capsules, suppositories, sachets, troches and lozenges, as well as liquid syrups, suspensions and elixirs.
  • the dosage form of the present invention may be a capsule containing the composition, preferably a powdered or granulated solid composition of the invention, within either a hard or a soft shell.
  • the shell may be made from gelatin and optionally contain a plasticizer such as glycerine and sorbitol, and an opacifying agent or colourant.
  • the active ingredient and excipients may be formulated into compositions and dosage forms according to methods known in the art.
  • a composition for tableting or capsule filling may be prepared by wet granulation.
  • wet granulation some or all of the active ingredient and excipients in powder form are blended and then further mixed in the presence of a liquid, typically water, that causes the powders to clump into granules.
  • the granulate is screened and/or milled, dried and then screened and/or milled to the desired particle size.
  • the granulate may then be tableted, or other excipients may be added prior to tableting, such as a glidant and/or a lubricant.
  • a tableting composition may be prepared conventionally by dry granulation.
  • the blended composition of the actives and excipients may be compacted into a slug or a sheet and then comminuted into compacted granules. The compacted granules may subsequently be compressed into a tablet.
  • a blended composition may be compressed directly into a compacted dosage form using direct compression techniques.
  • Direct compression produces a uniform tablet without granules.
  • Excipients that are particularly well suited for direct compression tableting include microcrystalline cellulose, spray dried lactose, dicalcium phosphate dihydrate and colloidal silica. The proper use of these and other excipients in direct compression tableting is known to those in the art with experience and skill in particular formulation challenges of direct compression tableting.
  • a capsule filling of the present invention may comprise any of the aforementioned blends and granulates that were described with reference to tableting, however, they are not subjected to a final tableting step.
  • composition of the invention may further comprise one or more additional active ingredients.
  • Further active ingredients may include other 5-HT 4 receptor agonists such as prucalopride, RS 67333 (l-(4-amino-5-chloro-2-methoxyphenyl)- 3-(l-n-butyl-4-piperidinyl)-l-propanone), RS 67506 (l-(4-amino-5-chloro-2- methoxyphenyl) -3- [1 - [2- [(methylsulphonyl) amino] ethyl] -4-piperidinyl] - 1 -propanone) , cisapride, renzapride, norcisapride, mosapride, zacopride, SB 205149, SC 53116, BIMU 1, and BIMU 8; proton pump inhibitors such as omeprazole, rabeprazole, pantoprazole, and lansoprazole; 5-HT
  • Tegaserod (leq) was taken in 3.3 volumes of methanol at 25-30 0 C. To this slurry was added a solution of pimelic acid (2eq) in 5 volumes of water and the mixture was stirred for about 30 minutes at 25-30 0 C. The precipitated salt was filtered and washed with 5 volumes of water and dried at 35°C under vacuum for about 2 hours. 1H-NMR indicated formation of tegaserod pimelate.
  • Ig of tegaserod pimelate was added to 25 volumes of ethyl acetate and heated to about

Abstract

Cette invention concerne un nouveau sel de tégasérod, à savoir le pimélate de tégasérod, et des procédés permettant de le préparer. L'invention concerne aussi des formes cristallines du nouveau sel et des compositions pharmaceutiques comprenant le nouveau sel. L'invention concerne par ailleurs des utilisations desdites compositions permettant de fournir des méthodes de traitement de patients souffrant d'affections gastro-intestinales.
PCT/GB2008/051123 2008-01-23 2008-11-27 Nouveau sel de tégasérod WO2009092993A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN141/KOL/2008 2008-01-23
IN141KO2008 2008-01-23

Publications (1)

Publication Number Publication Date
WO2009092993A1 true WO2009092993A1 (fr) 2009-07-30

Family

ID=40430242

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2008/051123 WO2009092993A1 (fr) 2008-01-23 2008-11-27 Nouveau sel de tégasérod

Country Status (1)

Country Link
WO (1) WO2009092993A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005058819A2 (fr) * 2003-12-16 2005-06-30 Teva Pharmaceutical Industries Ltd. Formes polymorphiques de la base du tegaserod et des sels de celui-ci
WO2006116953A1 (fr) * 2005-05-02 2006-11-09 Zentiva, A.S. Procede de preparation de tegaserod et de sels sélectionnés dérivés de ce composé

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005058819A2 (fr) * 2003-12-16 2005-06-30 Teva Pharmaceutical Industries Ltd. Formes polymorphiques de la base du tegaserod et des sels de celui-ci
WO2006116953A1 (fr) * 2005-05-02 2006-11-09 Zentiva, A.S. Procede de preparation de tegaserod et de sels sélectionnés dérivés de ce composé

Similar Documents

Publication Publication Date Title
US20110263649A1 (en) Crystalline form of lenalidomide and a process for its preparation
US6710184B2 (en) Crystalline solids of carvedilol and processes for their preparation
MX2007016179A (es) Formas cristalinas de o-desmetilvenlafaxina.
CA2686457A1 (fr) Nouvelles formes polymorphes
WO2005105740A2 (fr) Préparation de tégasérode et de maléate de tégasérode
WO2008149154A2 (fr) Nouveaux sels et nouvelles formes polymorphiques
US20110251254A1 (en) Novel salt of tegaserod
EP1685106A2 (fr) Forme de cristal de fexofenadine et ses processus de preparation
WO2009063247A1 (fr) Nouvelles formes cristallines
WO2009092993A1 (fr) Nouveau sel de tégasérod
WO2008149137A2 (fr) Benzoate de tégasérod et formes polymorphes
WO2008149136A1 (fr) Bésylate de tégasérod et formes polymorphes
WO2008149139A2 (fr) Nouvelles formes polymorphes
WO2008149138A1 (fr) Maléate de tégasérod et formes polymorphiques
WO2009141571A1 (fr) Nouveau polymorphe d'hydrochlorure de tegaserod
WO2009141573A1 (fr) Nouveau polymorphe d'adipate de tegaserod
WO2008149140A2 (fr) Nouvelles formes polymorphes
WO2009141572A1 (fr) Nouveau polymorphe
WO2009053732A1 (fr) Nouveau sel
WO2009063248A2 (fr) Nouvelles formes cristallines
WO2010015794A1 (fr) Nouvelles formes polymorphes
WO2009053733A2 (fr) Nouvelles formes cristallines
WO2009053754A2 (fr) Nouvelles formes cristallines
US20070043099A1 (en) Crystalline forms of carvedilol and processes for their preparation
WO2009053750A2 (fr) Nouvelles formes cristallines et amorphes

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08871553

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08871553

Country of ref document: EP

Kind code of ref document: A1