EP2260037A2 - Nouvelle forme polymorphe d'un dérivé de pyrazino[2,3-h][3]-benzazépine - Google Patents
Nouvelle forme polymorphe d'un dérivé de pyrazino[2,3-h][3]-benzazépineInfo
- Publication number
- EP2260037A2 EP2260037A2 EP09709821A EP09709821A EP2260037A2 EP 2260037 A2 EP2260037 A2 EP 2260037A2 EP 09709821 A EP09709821 A EP 09709821A EP 09709821 A EP09709821 A EP 09709821A EP 2260037 A2 EP2260037 A2 EP 2260037A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- varenicline base
- varenicline
- base
- polymorphic form
- hydrate
- 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.)
- Withdrawn
Links
- CFOPAPXJIQIMSO-UHFFFAOYSA-N 5h-pyrazino[2,3-h][3]benzazepine Chemical class C1=NC=CC2=CC3=NC=CN=C3CC2=C1 CFOPAPXJIQIMSO-UHFFFAOYSA-N 0.000 title 1
- JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 claims abstract description 86
- 229960004751 varenicline Drugs 0.000 claims abstract description 83
- 238000000034 method Methods 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 4
- 238000002411 thermogravimetry Methods 0.000 claims description 3
- 238000002441 X-ray diffraction Methods 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 6
- 238000000113 differential scanning calorimetry Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000000634 powder X-ray diffraction Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000004566 IR spectroscopy Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical class OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 1
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 150000008038 benzoazepines Chemical class 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229940124535 smoking cessation aid Drugs 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000000547 structure data Methods 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- TWYFGYXQSYOKLK-CYUSMAIQSA-N varenicline tartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 TWYFGYXQSYOKLK-CYUSMAIQSA-N 0.000 description 1
- 229960003977 varenicline tartrate Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
Definitions
- the present invention relates to a novel crystalline form of varenicline base, i.e. a hydrate of varenicline base, designated herein as Form II, and to a method for obtaining and preparing the same.
- Varenicline (Compound I) is the international commonly accepted name for 7, 8, 9, 10-tetrahydro-6, 10- methano-6H-pyrazino [2 , 3-h] [3] benzazepine (which is also known as 5, 8, 14-triazatetracyclo [ 10.3.1. O 2 ' 11 . O 4 ' 9 ] - hexadeca-2 (11) , 3, 5, 7, 9-pentaene) , and has an empirical formula of C13H13N3 and a molecular weight of 211.26.
- varenicline L-tartrate The L-tartrate salt of varenicline has been selected for medical purpose and is commercially marketed for the treatment of smoking addiction.
- Varenicline L-tartrate is a partial agonist selective for ⁇ 4 ⁇ 2 nicotinic acetylcholine receptor subtypes.
- varenicline L-tartrate is marketed under the name ChantixTM, and is indicated as an aid to smoking cessation treatment.
- Varenicline base and its pharmaceutically acceptable acid addition salts are described in U.S. Patent No. 6,410,550.
- Example 26 of U.S. Patent No. 6,410,550 describes the preparation of varenicline base, which is subsequently converted into its hydrochloride salt.
- varenicline base is isolated from a dichloromethane solution to afford the compound as a light yellow oil which solidified upon standing to give a solid.
- U.S. Patent No. 6,410,550 only reports the melting point of this solid (138-140 0 C), and does not provide the crystalline data of said compound. Namely, there is no crystal structure data in the literature regarding varenicline base. In our hands, the varenicline base polymorphic form obtained in U.S. Patent No. 6,410,550 has been isolated and characterized as an anhydrous crystalline solid, and has been denominated herein as Form I . International publication No. WO 2008/060487 describes that anhydrous varenicline base shows polymorphism. More precisely, four different crystalline forms of varenicline base are provided in this reference (designated therein as Forms A, C, D, and E) . Polymorphism is very common among pharmaceutical substances.
- varenicline base It is commonly defined as the ability of any substance to exist in two or more crystalline phases that have a different arrangement and/or conformation of the molecules in the crystal lattice. Different polymorphs differ in their physical properties such as melting point, solubility, chemical reactivity, etc. These properties may appreciably influence pharmaceutical properties such as dissolution rate and bioavailability.
- identifying and isolating new polymorphic forms of varenicline base that may have superior chemical and/or physical properties. Further, it would be desirable to have reliable processes for producing varenicline base in one or more of its new polymorphic forms. Additionally, the new polymorphic forms of varenicline base could be used to prepare improved pharmaceutical compositions .
- the invention relates generally to a crystalline polymorphic form of 7, 8, 9, 10-tetrahydro-6, 10-methano-6H- pyrazino [2, 3-h] [3] benzazepine, varenicline base, i.e. a hydrate of varenicline base, designated herein as Form II, and to a method for preparing and obtaining the same .
- varenicline base i.e. a hydrate of varenicline base, designated herein as Form II
- Figure 1 illustrates the X-ray powder diffractogram (XRD) of varenicline base Form I obtained in Example 1.
- FIG. 1 illustrates the Infrared (IR) spectrum of varenicline base Form I obtained in Example 1.
- Figure 3 illustrates the Differential Scanning Calorimetry (DSC) thermogram in an open pan of varenicline base Form I obtained in Example 1.
- Figure 4 illustrates the X-ray powder diffractogram (XRD) of varenicline base Form II, i.e. a hydrate of varenicline base, obtained in Example 2.
- XRD X-ray powder diffractogram
- Figure 5 illustrates the Infrared (IR) spectrum of varenicline base Form II, i.e. a hydrate of varenicline base, obtained in Example 2.
- Figure 6 illustrates the X-ray powder diffractogram (XRD) of varenicline base mixture of Form I and Form II obtained in Example 3.
- IR Infrared
- XRD X-ray powder diffractogram
- varenicline base can exist in a new crystalline form, i.e. a hydrate of varenicline base.
- This new form of varenicline base has been prepared and characterized as described herein and is referred to herein as Form II.
- our inventors have isolated anhydrous crystalline solid varenicline base from a dichloromethane solution.
- the obtained crystalline polymorphic form of varenicline base (i.e. prior art varenicline base) has been designated herein as Form I.
- Varenicline base polymorphic Form I has been characterized herein by X-ray powder diffraction (XRD) , Infrared spectrometry (IR), and Differential Scanning Calorimetry (DSC) (see Figures 1, 2, and 3, respectively) .
- XRD X-ray powder diffraction
- IR Infrared spectrometry
- DSC Differential Scanning Calorimetry
- a first aspect of the present invention includes varenicline base polymorphic Form II characterized by its X-ray powder diffraction pattern (XRD) .
- Figure 4 illustrates the XRD (2 ⁇ ) ( ⁇ 0.2°) of varenicline base polymorphic Form II which has its main peaks at approximately 8.8, 9.3, 10.7, 12.0, 13.8, 14.4, 16.2, 17.2, 17.8, 18.6, 20.0, 20.7, 20.8, 21.2, 26.9 and 27.8° with further peaks at 15.6, 19.0, 21.6, 22.8, 28.4 and 28.9° .
- varenicline base polymorphic Form II has been characterized by Infrared (IR) spectrum.
- Figure 5 illustrates the IR spectrum of varenicline base polymorphic Form II.
- Another aspect of the present invention is to provide a process for preparing varenicline base Form II, said process comprising (i) dissolving varenicline base in a selected solvent comprising water, to obtain a solution, and (ii) removing the solvent from said solution, to give varenicline base Form II.
- the selected solvent comprising water preferably is water.
- the step (ii) of removing the solvent from said solution is carried out by evaporating the solvent.
- the step (ii) of removing the solvent from said solution is carried out by leaving the product to precipitate to obtain a suspension, and filtering the suspension.
- the varenicline base used for preparing varenicline base Form II can be either varenicline base obtained by a known method.
- varenicline base polymorphic Form II of the invention is a hydrate of varenicline base .
- Another aspect of the invention includes a hydrate of varenicline base.
- the hydrate of varenicline base of the invention shows a loss on drying of about 4.8% on heating between about 85° and 115 0 C, as determined by Thermal Gravimetric Analysis (TGA) .
- Another aspect of the invention includes the use of varenicline base crystalline Form II, i.e. a hydrate of varenicline base, for preparing varenicline base polymorphic Form I, i.e. anhydrous varenicline base.
- the invention includes a process for preparing varenicline base polymorphic Form I, said process comprising removing the water from varenicline base Form II by means of azeotropic distillation.
- the invention includes a process for preparing varenicline base polymorphic Form I, said process comprising removing the water from varenicline base Form II by means of heat- drying said varenicline base Form II.
- the heat-drying can be carried out under reduced pressure.
- the present invention also relates to mixtures of varenicline base Form I and Form II.
- the inventors have found that by dissolving varenicline base in a solvent comprising water and ethanol and removing the solvent, varenicline base mixture of Form I and Form II is obtained (see Example 3) .
- Another aspect of the invention includes the use of varenicline base crystalline Form II for preparing and obtaining pharmaceutically acceptable salts of varenicline .
- Another aspect of the invention includes the use of varenicline base crystalline Form II for preparing and obtaining varenicline L-tartrate.
- DSC measurement was performed in vented pan at a scan rate of 10° C/minute from 25.0° C to 270.0° C under a nitrogen purge with a DSC823 available from Mettler- Toledo.
- Varenicline base (100 mg) was dissolved in water (0.5 mL) and heated to 70 0 C for one hour. The solution was allowed to cool to room temperature, and stirred for 24 hours at this temperature before evaporation of the solvent (by opening the vial and allowing to evaporate under ambient temperature conditions) .
- Example 3 Preparation of a mixture of varenicline base Form I and Form II
- Varenicline base (100 mg) was dissolved in a 20:80 mixture of water and ethanol (0.5 mL) and heated to 70 0 C for one hour. The solution was allowed to cool to room temperature, and stirred for 24 hours at this temperature before evaporation of the solvent (by opening the vial and allowing to evaporate under ambient temperature conditions) .
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Addiction (AREA)
- General Chemical & Material Sciences (AREA)
- Psychiatry (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (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)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
L'invention porte d'une manière générale sur une forme polymorphe cristalline de 7, 8, 9, 10-tétrahydro-6, 10-méthano-6H-pyrazino[2,3-h][3]benzazépine, la varénicline base, à savoir un hydrate de varénicline base, appelée ici Forme II, ainsi que sur un procédé pour préparer et obtenir celle-ci.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6603208P | 2008-02-15 | 2008-02-15 | |
| PCT/EP2009/051727 WO2009101185A2 (fr) | 2008-02-15 | 2009-02-13 | Nouvelle forme polymorphe d'un dérivé de pyrazino[2,3-h][3]-benzazépine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP2260037A2 true EP2260037A2 (fr) | 2010-12-15 |
Family
ID=40852121
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP09709821A Withdrawn EP2260037A2 (fr) | 2008-02-15 | 2009-02-13 | Nouvelle forme polymorphe d'un dérivé de pyrazino[2,3-h][3]-benzazépine |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP2260037A2 (fr) |
| WO (1) | WO2009101185A2 (fr) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11602537B2 (en) | 2022-03-11 | 2023-03-14 | Par Pharmaceutical, Inc. | Varenicline compound and process of manufacture thereof |
| EP4241775A1 (fr) | 2022-03-11 | 2023-09-13 | Par Pharmaceutical, Inc. | Comprimé de varénicline et son procédé de fabrication |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE386024T1 (de) * | 1997-12-31 | 2008-03-15 | Pfizer Prod Inc | Arylkondensierte azapolycyclische derivate |
| CZ20011726A3 (cs) * | 2000-05-26 | 2002-02-13 | Pfizer Products Inc. | Způsob reakční krystalizace, který umoľňuje řídit velikost částic |
| CZ20032814A3 (cs) * | 2001-04-20 | 2004-08-18 | Pfizeráproductsáinc | Způsob přípravy �Ź@@substituovaných indenů a aryl@kondezovaných azapolycyklických sloučenin |
-
2009
- 2009-02-13 EP EP09709821A patent/EP2260037A2/fr not_active Withdrawn
- 2009-02-13 WO PCT/EP2009/051727 patent/WO2009101185A2/fr not_active Ceased
Non-Patent Citations (1)
| Title |
|---|
| See references of WO2009101185A2 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11602537B2 (en) | 2022-03-11 | 2023-03-14 | Par Pharmaceutical, Inc. | Varenicline compound and process of manufacture thereof |
| US11717524B1 (en) | 2022-03-11 | 2023-08-08 | Par Pharmaceutical, Inc. | Varenicline compound and process of manufacture thereof |
| EP4241775A1 (fr) | 2022-03-11 | 2023-09-13 | Par Pharmaceutical, Inc. | Comprimé de varénicline et son procédé de fabrication |
| US11779587B2 (en) | 2022-03-11 | 2023-10-10 | Par Pharmaceutical, Inc. | Vareniciline compound and process of manufacture thereof |
| US11872234B2 (en) | 2022-03-11 | 2024-01-16 | Par Pharmaceutical, Inc. | Vareniciline compound and process of manufacture thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009101185A2 (fr) | 2009-08-20 |
| WO2009101185A3 (fr) | 2009-12-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2017008773A1 (fr) | Formes cristallines d'acide obéticholique | |
| CZ20032916A3 (cs) | 5,8,14-Triazatetracyklo (10.3.1.02,11.04,9)-hexadeka-2(11),3,5,7,9-pentaen-tartrát | |
| CA2814357C (fr) | Hydrate de tartrate de 1-{(2s)-2-amino-4-[2,4-bis(trifluoromethyl)-5,8-dihydropyrido[3,4-d]pyrimidin-7(6h)-yl]-4-oxobutyl}-5,5-difluoropiperidin-2-one | |
| WO2014121901A1 (fr) | Formes polymorphes | |
| EP2502917A1 (fr) | Formes cristallines à l'état solide de 4-(2-ethyl-5-fluoro-2,3-dihydro-1H-inden-2-yl)-1H-imidazole | |
| US8440825B2 (en) | Fumaric acid salt of varenicline | |
| WO2016131431A1 (fr) | Formes solides d'empagliflozine | |
| WO2007109799A2 (fr) | Polymorphes de malate d'eszopiclone | |
| EP2773618A1 (fr) | Procédé amélioré pour la préparation d'étoricoxibe et de polymorphes de celui-ci | |
| EP2342195B1 (fr) | Formes cristallines d un sel de malate de 2-indolinone à substitution 3-pyrrole | |
| US8389562B2 (en) | Polymorphic forms of a 3-pyrrole substituted 2-indolinone | |
| WO2009118657A2 (fr) | Forme polymorphe d'un dérivé de mésylate d'amino-indane | |
| WO2009101185A2 (fr) | Nouvelle forme polymorphe d'un dérivé de pyrazino[2,3-h][3]-benzazépine | |
| EP1641741A1 (fr) | Polymorphe b du chlorhydrate de levalbuterol | |
| JP7152122B2 (ja) | エダラボン塩 | |
| EP2189461B1 (fr) | Hydrochlorure crystalline d'irinotecan et procédés pour sa préparation | |
| WO2017221215A1 (fr) | Sels de lenvatinib | |
| WO2017036884A1 (fr) | Co-cristal de lésinurad, forme libre/ester éthylique de lésinurad | |
| WO2013170243A1 (fr) | Polymorphe forme 5 de 7-(tert-butyl-d9)-3-(2,5-difluorophényl)6((1-méthyl-1h-1,2,4-triazol-5-yl)méthoxy)-[1, 2,4]triazolo[4,3-b]pyridazine | |
| WO2015170340A2 (fr) | Nouveaux polymorphes de chlorhydrate de sitagliptine, procédés de préparation et composition pharmaceutique de ceux-ci | |
| WO2008038143A2 (fr) | Nouvelles formes solides du rimonabant et procédés de synthèse pour la préparation de celles-ci | |
| HUE028550T2 (en) | Polymorphs of 6- (Piperidin-4-yloxy) -2H-isoquinolin-1-one hydrochloride | |
| US8779005B2 (en) | Salts of desvenlafaxine and a method of their preparation | |
| US20070173496A1 (en) | Novel polymorph E of Olanzapine and preparation of anhydrous non-solvated crystalline polymorphic Form I of 2-methyl-4(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine (Olanzapine Form I) from the polymorphic Olanzapine Form E | |
| AU2005277361A1 (en) | Process for the production of levorphanol and related compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN |
|
| 17P | Request for examination filed |
Effective date: 20100914 |
|
| AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK TR |
|
| AX | Request for extension of the european patent |
Extension state: AL BA RS |
|
| 18W | Application withdrawn |
Effective date: 20101104 |
|
| RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: WINTER, STEPHEN, BENEDICT, DAVID |
|
| RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: WINTER, STEPHEN, BENEDICT, DAVID |