WO2007010555A2 - Nouvelles formes cristallines d'hydrochlorure de moxifloxacine et procede de preparation associe - Google Patents
Nouvelles formes cristallines d'hydrochlorure de moxifloxacine et procede de preparation associe Download PDFInfo
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- WO2007010555A2 WO2007010555A2 PCT/IN2006/000244 IN2006000244W WO2007010555A2 WO 2007010555 A2 WO2007010555 A2 WO 2007010555A2 IN 2006000244 W IN2006000244 W IN 2006000244W WO 2007010555 A2 WO2007010555 A2 WO 2007010555A2
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- Prior art keywords
- moxifloxacin hydrochloride
- crystalline form
- moxifloxacin
- hydrochloride
- preparation
- Prior art date
Links
- 229960005112 moxifloxacin hydrochloride Drugs 0.000 title claims abstract description 68
- 238000000034 method Methods 0.000 title claims abstract description 28
- 230000008569 process Effects 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- IDIIJJHBXUESQI-DFIJPDEKSA-N moxifloxacin hydrochloride Chemical compound Cl.COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 IDIIJJHBXUESQI-DFIJPDEKSA-N 0.000 title claims abstract 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 34
- 239000002904 solvent Substances 0.000 claims description 29
- 229960003702 moxifloxacin Drugs 0.000 claims description 23
- FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 claims description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- 238000001914 filtration Methods 0.000 claims description 16
- 239000007787 solid Substances 0.000 claims description 16
- 239000000463 material Substances 0.000 claims description 15
- 238000010992 reflux Methods 0.000 claims description 15
- 238000002441 X-ray diffraction Methods 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 9
- 230000001476 alcoholic effect Effects 0.000 claims description 9
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 7
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 6
- 239000010949 copper Substances 0.000 claims description 6
- 229910052802 copper Inorganic materials 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 4
- 230000005855 radiation Effects 0.000 claims description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- 239000012670 alkaline solution Substances 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 1
- 150000001298 alcohols Chemical class 0.000 claims 1
- 239000008096 xylene Substances 0.000 claims 1
- SKZIMSDWAIZNDD-WJMOHVQJSA-N 7-[(4as,7as)-1,2,3,4,4a,5,7,7a-octahydropyrrolo[3,4-b]pyridin-6-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid;hydrate;hydrochloride Chemical compound O.Cl.COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 SKZIMSDWAIZNDD-WJMOHVQJSA-N 0.000 description 63
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 11
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 229960004592 isopropanol Drugs 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
- -1 Moxifloxacin hydrochloride compound Chemical class 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 150000004682 monohydrates Chemical class 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- KSCPLKVBWDOSAI-NKWVEPMBSA-N (4as,7as)-2,3,4,4a,5,6,7,7a-octahydro-1h-pyrrolo[3,4-b]pyridine Chemical compound N1CCC[C@H]2CNC[C@H]21 KSCPLKVBWDOSAI-NKWVEPMBSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 239000003518 caustics Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- PPNCOQHHSGMKGI-UHFFFAOYSA-N 1-cyclononyldiazonane Chemical compound C1CCCCCCCC1N1NCCCCCCC1 PPNCOQHHSGMKGI-UHFFFAOYSA-N 0.000 description 1
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 201000005010 Streptococcus pneumonia Diseases 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000009477 glass transition Effects 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 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
- C07D471/04—Ortho-condensed systems
Definitions
- the present invention relates to a novel crystalline forms of Moxifloxacin Hydrochloride, Particularly the present invention relates to a novel crystalline Form-X and Form-Y of Moxifloxacin Hydrochloride and process for preparing the same, Moxifloxacin hydrochloride chemically known as l-Cyclopropyl-6-fluoro-l,4-dihydro-8- methoxy-7[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridine-6-yl]-4-oxo-3-quinoline carboxylic acid hydrochloride compound of formula (I) as shown below.
- Moxifloxacin monohydrochloride is a synthetic broad-spectrum antibacterial agent.
- the active moiety, Moxifloxacin has been shown to be clinically active against most strains of microorganisms such as aerobic gram-positive microorganism including staphylococcus aureus, streptococcus pneumonia (penicillin-susceptible strains) and streptococcus pyogenes, aerobic gram-negative microorganisms including haemophilus influenza hemophilus parainfluenzae, klebisiella pneumonia.
- Polymorphism can be defined as the ability of the same chemical substance to exist in different crystalline structures.
- the different structures are referred to as polymorphs, polymorphic modification or polymorphic Forms.
- Moxifloxacin hydrochloride is l-Cyclopropyl-6-fluoro-l,4-dihydro-8-methoxy-7[(4aS, 7aS)-octahydro-6H-pyrrolo [3 ,4-b]pyridine-6-yl] -4-oxo-3 -quinolinecarboxylic acid monohydrochloride, which is a hydrochloric acid salt of l-Cyclopropyl-6-fiuoro-l,4- dihydro-8-methoxy-7[(4aS, 7aS)-octahydro-6H-pyrrolo[3,4-b]pyridine-6-yl]-4-oxo-3- quinolinecarboxylic acid in 1:1 mole ratio.
- Moxifloxacin hydrochloride As a molecule Moxifloxacin hydrochloride is described U.S. 5,607,953, of which entire content is incorporated by reference herein.
- polymorphic forms of the same drug may have substantial differences in certain pharmaceutically important properties such as dissolution characteristics and bioavailability as well as stability of the drug.
- more different crystalline form may have difference particle size, hardness and glass transition temperature.
- one crystalline form may provide significant advantages over other crystalline forms of the same drug in solid dosage form manufacture process such as accurate measurement of the active ingredients, easier filtration, or more improved stability during granulation or storage.
- a particular process suitable for crystalline form may also provide drug manufacturers several advantage such economically or environmentally suitable solvents or process or higher purity or yield of the desired product.
- Form-Ill prepared as per the patent '091619 examples lead to initially anhydrous form, but when we kept it open for 30 mts., in petri dish and as well as in stability by a normal packing condition, it picked up moisture and converted to hydrated form.
- WO 2005/054240 discloses two novel crystalline forms, designated as Form A and Form B and process for preparing the same, which comprises of dissolving Moxifloxacin anhydrous or monohydrate form in a suitable solvent like ethanol and isopropanol and refluxing the same and cooling the reaction then isolating the product (Form A) and the resulting product reslurrying in alcohol at reflux to get Form B.
- a suitable solvent like ethanol and isopropanol
- WO 2004 / 091619 patent disclose X-ray diffraction pattern of the Anhydrous Form I, the disclosed 20 values are 5.8, 8.6, 10.3, 11.6, 13.6, 14.5, 15.0, 15.8, 17.3, 17.5, 18.3, 18.9,
- the object of the present invention is to provide the novel crystalline form of Moxifloxacin hydrochloride and process for preparing the same, which is stable as well as remains anhydrous for long term.
- the crystalline form of the present invention is characterized by X-ray diffractogram pattern.
- novel crystalline form of Moxifloxacin hydrochloride may be well suited for pharmaceutical formulations and can be used in the antibacterial treatment.
- Moxifloxacin hydrochloride chemically known as l-Cyclopropyl-6-fluoro-l,4-dihydro-8- methoxy-7 [(4aS,7aS)-octahydro-6H-pyrrolo [3 ,4-b]pyridine-6-yl]-4-oxo-3 -quinoline carboxylic acid hydrochloride which have the following formula (I) as shown below.
- the first aspect of the present invention is to provide a novel crystalline anhydrous Form- X of Moxifloxacin hydrochloride, which is stable and can be scaled up with easier operation.
- the crystalline Form-X of moxifloxacin hydrochloride may be characterized by an X-ray diffraction pattern, expressed in terms of 2 ⁇ angles and obtained with a difractometer equipped with a copper K, X-radiation source, where in the X-ray powder diffraction pattern includes three or more peaks selected from the group consisting of peaks with 2 theta angles with 5.7, 7.1, 8.5, 10.2, 13.8, 14.0 15.1, 15.6,16.5, 16.8, 18.2, 19.7, 21.6, 22.2, 22.4, 24.3, 25.1, 25.7, 26.4, 28.9, 29.5, 29.8, 30.4, 32.0, 32.3, 33.3, 34.0, 34.7, 35.9, 36.6, 37.2, 37.5, 40.0, 41.2, 41.7, 42.9, 43.8, 4
- the crystalline Form-X of Moxifloxacin hydrochloride may also be characterized by an X-ray diffraction pattern, expressed in terms of 2 theta angles and obtained with a difractometer equipped with a copper K, X-radiation source ,where in the X-ray powder diffraction pattern includes difference of the 2 theta values between 10.2 and 12.2, no peaks were observed.
- the crystalline Form X of anhydrous Moxifloxacin hydrochloride in the composition of this aspect of the invention may be characterized by the XRD pattern as described.
- the second aspect of the present invention is to provide the process for preparing the crystalline Form-X of Moxifloxacin hydrochloride compound of formula(I) which comprises; i) Refluxing the Moxifloxacin hydrochloride azeotropically in a suitable hydrocarbon solvents, ii) Isolating the product by cooling and filtration and drying the material to get the Moxifloxacin hydrochloride Form-X.
- Moxifloxacin hydrochloride and one or more pharmaceutically acceptable carriers are diluents.
- the pharmaceutical composition may also include one or more additional active ingredients.
- the invention also relates to a method of preventing or treating allergic syndromes, by administering to a patient in need of such treatment an effective amount of crystalline
- the Third aspect of the present invention is to provide a novel crystalline Form-Y of Moxifloxacin hydrochloride, which is also stable and can be scaled up with easier operation.
- the crystalline Form-Y of Moxifloxacin hydrochloride may be characterized by an X-ray defraction pattern, expressed in terms of 2 ⁇ angles and obtained with a difractometer equipped with a copper K X-radiation source, where in the X-ray powder diffraction pattern includes three or more peaks selected from the group consisting of peaks with 2 theta angles with 5.8, 6.4, 7.7, 8.1,8.4, 9.5, 10.0, 12.0, 13.0, 13.7, 14.5, 15.4, 16.4, 17.1, 17.9, 19.1, 19.6, 19.9, 20.4, 21.2, 23.3, 24.0, 25.8, 26.9, 27.7, 28.3, 28.9, 31.8, 39.1, 40.4 degrees.
- the crystalline Form-Y of Moxifloxacin hydrochloride may also be characterized by an
- the crystalline Form-Y of Moxifloxacin hydrochloride in the composition of this aspect of the invention may be characterized by the XRD pattern as described.
- the fourth aspect of the present invention is to provide the process for preparing the crystalline Form-Y of Moxifloxacin hydrochloride which comprises of. i) Heating the suspended Moxifloxacin in alcoholic solvents, ii) Dissolving the compound by adjusting the pH, iii) Filtering, and adjusting the pH, iv) Stirring for 1 to 3 hours, v) Isolating the product by filtration and drying the material to get the
- compositions that includes the crystalline Form-Y of Moxifloxacin hydrochloride and one or more pharmaceutically acceptable carriers are diluents.
- the pharmaceutical composition may also include one or more additional active ingredients.
- the invention also relates to a method of preventing or treating allergic syndromes, by administering to a patient in need of such treatment an affective amount of crystalline Form-Y of Moxifloxacin hydrochloride.
- Figure- 1 is a sample of X-ray powder difractogram of the crystalline Form-X of Moxifloxacin Hydrochloride.
- Figure-2 is a sample of X-ray powder difractogram of the crystalline Form-Y of Moxifloxacin Hydrochloride.
- the present invention relates to a novel crystalline forms of Moxifloxacin Hydrochloride, Particularly the present invention relates to novel crystalline Form-X and Form-Y of Moxifloxacin Hydrochloride and process for preparing the same, Moxifloxacin hydrochloride is chemically known as l-Cyclopropyl-6-fmoro-l,4-dihydro- 8-methoxy-7[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridine-6-yl]-4-oxo-3-quinoline carboxylic acid hydrochloride compound of formula (I) as shown below.
- a compound is a chemical substance that includes molecules of the same chemical structure.
- Pharmaceutically acceptable means that which is useful in preparing a pharmaceutical composition that is generally non-toxic and is not biologically undesirable and includes that which is acceptable for veterinary use and human pharmaceutical use.
- the first aspect of the invention is to provide the new crystalline Form-X of anhydrous Moxifloxacin monohydrochloride, which is different from the Form- I and Form- III of the '752 and 091619 patents.
- a process including refluxing azeotropically a mixture of moxifloxacin hydrochloride and a solvent selected from the group consisting of aliphatic or aromatic hydrocarbons solvent to form a mixture, cooling the refluxed mixture until solid separates, and isolating said solid thereby obtaining said crystalline Form-X of Moxifloxacin hydrochloride.
- the crystalline Form-X of moxifloxacin monohydrochloride produced by the inventors was characterized by an X-ray powder diffraction pattern.
- An example of one of X-ray diffraction analysis is shown in Figure- 1, and the characteristic 2-theta values (in degrees) in the X-ray diffractograms are as follows;
- the X-ray diffractogram was measured on a Siemens D/Max-5000 model powder X-ray diffractometer with Cu K alpha- 1 radiation source.
- the crystalline Form-X of anhydrous moxifloxacin hydrochloride may also be characterized by an X-ray powder diffraction pattern includes absence of peaks at 2 theta values between 10.2 and 12.2 is the major difference from the anhydrous Form I and Form-Ill.
- the second aspect of the present invention is to provide a process for preparing the crystalline Form-X of Moxifloxacin hydrochloride compound of formula (I) which comprises; i) Refluxing azeotropically the Moxifloxacin hydrochloride in hydrocarbon solvents such as, cyclohexane, n-Heptane and Toluene, ii) Isolating the material by cooling the reaction mass followed by filtering the separated solid and optionally washing the material with alcoholic solvent, iii) Drying the compound under vacuum between 80 to 90°C to afford a Form X of anhydrous moxifloxacin hydrochloride.
- hydrocarbon solvents such as, cyclohexane, n-Heptane and Toluene
- the third aspect of the present invention provides new crystalline Form-Y of Moxifloxacin monohydrochloride, which is different from the Form I, Form-II and Form III of the '752 and 091619 patents and the present Form-X.
- a process including, heating the mixture of moxifloxacin and a solvent selected from the group of alcoholic solvent and adjusting the pH to 7.5 -8.5 with alkali solution and filtering to get a clear solution. Adjusting the pH of the filtrate to below 2.0 with aqueous HCl. and isolating the separated solid there by obtaining crystalline Form-Y of moxifloxacin hydrochloride.
- the crystalline Form-Y of Moxifloxacin monohydrochloride produced by the inventors was characterized by an X-ray powder diffraction pattern.
- An example of one of X-ray diffraction analysis is shown in Figure- 2, and the characteristic 2-theta values (in degrees) in the X-ray diffractograms are as follows;
- the fourth aspect of the present invention is to provide the process for preparing the crystalline Form-Y of Moxifloxacin hydrochloride which comprises of;
- the present invention also discloses a process for the preparation of Moxifloxacin hydrochloride monohydrate which comprises of;
- Another embodiment of the present invention discloses a process for the preparation of Anhydrous Moxifloxacin hydrochloride which comprises of;
- Example 1 Preparation of novel crystalline Form -Y of moxifloxacin hydrochloride.
- Example 2 Preparation of novel crystalline Form -X of moxifloxacin hydrochloride.
- Example 3 Preparation of novel crystalline form X of anhydrous moxifloxacin hydrochloride.
- Example 4 Preparation of novel crystalline form X of anhydrous moxifloxacin hydrochloride.
- Example 6 One-pot Preparation of Moxifloxacin hydrochloride monohydrate.
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
L'invention concerne de nouvelles formes cristallines d'hydrochlorure de moxifloxacine et un procédé de préparation associé
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN948CH2005 | 2005-07-15 | ||
| IN948/CHE/2005 | 2005-07-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2007010555A2 true WO2007010555A2 (fr) | 2007-01-25 |
| WO2007010555A3 WO2007010555A3 (fr) | 2007-04-12 |
Family
ID=37669239
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IN2006/000244 WO2007010555A2 (fr) | 2005-07-15 | 2006-07-13 | Nouvelles formes cristallines d'hydrochlorure de moxifloxacine et procede de preparation associe |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2007010555A2 (fr) |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007148137A1 (fr) * | 2006-06-23 | 2007-12-27 | Generics [Uk] Limited | Nouvelle forme hydrate du monochlorhydrate de moxifloxacine |
| WO2008028959A1 (fr) * | 2006-09-08 | 2008-03-13 | Quimica Sintetica, S. A. | Forme cristalline d'hydrochlorure de moxifloxacine |
| WO2008059223A3 (fr) * | 2006-11-13 | 2008-07-31 | Cipla Ltd | Procédé pour la synthèse de chlorhydrate de moxifloxacine |
| WO2008095964A1 (fr) * | 2007-02-07 | 2008-08-14 | Química Sintética, S.A. | Forme cristalline de la base de moxifloxacine |
| ES2316270A1 (es) * | 2007-02-07 | 2009-04-01 | Quimica Sintetica, S.A. | Nueva forma cristalina de moxifloxacino clorhidrato anhidrato forma iv. |
| WO2009087151A1 (fr) * | 2008-01-08 | 2009-07-16 | Chemo Ibérica, S.A. | Formes polymorphes de chlorhydrate de moxifloxacine et leurs procédés de préparation |
| EP2154137A1 (fr) | 2008-08-04 | 2010-02-17 | Chemo Ibérica, S.A. | Formule cristalline à base de moxifloxacine |
| CN101973992A (zh) * | 2010-10-09 | 2011-02-16 | 河南省健康伟业医药科技有限公司 | 一种盐酸莫西沙星的合成方法 |
| US20110212990A1 (en) * | 2008-11-06 | 2011-09-01 | Hetero Research Foundation | Novel polymorph of moxifloxacin hydrochloride |
| CN102276603A (zh) * | 2011-07-14 | 2011-12-14 | 福建省福抗药业股份有限公司 | 一种盐酸莫西沙星的清洁制备方法 |
| CN102603738A (zh) * | 2012-02-24 | 2012-07-25 | 天津市汉康医药生物技术有限公司 | 一种稳定的盐酸莫西沙星化合物 |
| CN102924449A (zh) * | 2012-10-30 | 2013-02-13 | 重庆福安药业集团庆余堂制药有限公司 | 盐酸莫西沙星h晶型及其制备方法和药物组合物 |
| CN102952131A (zh) * | 2011-08-29 | 2013-03-06 | 成都国为医药科技有限公司 | 一种盐酸莫西沙星的制备方法 |
| CN112759590A (zh) * | 2020-11-19 | 2021-05-07 | 内蒙古源宏精细化工有限公司 | 一种莫西沙星的制备方法 |
| CN115536658A (zh) * | 2022-09-09 | 2022-12-30 | 天方药业有限公司 | 一种盐酸莫西沙星一水合物制备方法 |
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| US20090201282A1 (en) * | 2008-02-11 | 2009-08-13 | Qualcomm Mems Technologies, Inc | Methods of tuning interferometric modulator displays |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2521398C (fr) * | 2003-04-09 | 2011-03-22 | Dr. Reddy's Laboratories Limited | Forme cristalline iii de chlorhydrate de moxifloxacine anhydre et procede de preparation de cette derniere |
| EP1651630A1 (fr) * | 2003-08-05 | 2006-05-03 | Matrix Laboratories Ltd | Procede ameliore permettant de preparer un hydrochlorure de moxifloxacine |
| WO2005054240A1 (fr) * | 2003-11-20 | 2005-06-16 | Chemi Spa | Polymorphes d'hydrochlorure d'acide 1-cyclopropyl-7-((s,s)-2,8-diazadicyclo(4.3.0)non-8-yl)-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinoline carboxylique, et leurs methodes de preparation |
-
2006
- 2006-07-13 WO PCT/IN2006/000244 patent/WO2007010555A2/fr active Application Filing
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| WO2007148137A1 (fr) * | 2006-06-23 | 2007-12-27 | Generics [Uk] Limited | Nouvelle forme hydrate du monochlorhydrate de moxifloxacine |
| WO2008028959A1 (fr) * | 2006-09-08 | 2008-03-13 | Quimica Sintetica, S. A. | Forme cristalline d'hydrochlorure de moxifloxacine |
| ES2303768A1 (es) * | 2006-09-08 | 2008-08-16 | Quimica Sintentica, S.A. | Nueva forma cristalina de moxifloxacino clorhidrato. |
| ES2303768B1 (es) * | 2006-09-08 | 2009-06-05 | Quimica Sintetica, S.A. | Nueva forma cristalina de moxifloxacino clorhidrato. |
| US8198451B2 (en) | 2006-11-13 | 2012-06-12 | Cipla Limited | Process for the synthesis of moxifloxacin hydrochloride |
| WO2008059223A3 (fr) * | 2006-11-13 | 2008-07-31 | Cipla Ltd | Procédé pour la synthèse de chlorhydrate de moxifloxacine |
| ES2316270A1 (es) * | 2007-02-07 | 2009-04-01 | Quimica Sintetica, S.A. | Nueva forma cristalina de moxifloxacino clorhidrato anhidrato forma iv. |
| ES2311391A1 (es) * | 2007-02-07 | 2009-02-01 | Quimica Sintetica, S.A. | Forma cristalina de moxifloxacino base. |
| ES2311391B1 (es) * | 2007-02-07 | 2009-12-22 | Quimica Sintetica, S.A. | Forma cristalina de moxifloxacino base. |
| ES2316270B1 (es) * | 2007-02-07 | 2010-02-09 | Quimica Sintetica, S.A. | Nueva forma cristalina de moxifloxacino clorhidrato anhidro forma iv . |
| WO2008095964A1 (fr) * | 2007-02-07 | 2008-08-14 | Química Sintética, S.A. | Forme cristalline de la base de moxifloxacine |
| WO2009087151A1 (fr) * | 2008-01-08 | 2009-07-16 | Chemo Ibérica, S.A. | Formes polymorphes de chlorhydrate de moxifloxacine et leurs procédés de préparation |
| EP2083010A1 (fr) | 2008-01-08 | 2009-07-29 | Chemo Ibérica, S.A. | Formes polymorphes d'hydrochlorure de moxifloxacine et leurs procédés de préparation |
| EP2154137A1 (fr) | 2008-08-04 | 2010-02-17 | Chemo Ibérica, S.A. | Formule cristalline à base de moxifloxacine |
| US20110212990A1 (en) * | 2008-11-06 | 2011-09-01 | Hetero Research Foundation | Novel polymorph of moxifloxacin hydrochloride |
| CN101973992A (zh) * | 2010-10-09 | 2011-02-16 | 河南省健康伟业医药科技有限公司 | 一种盐酸莫西沙星的合成方法 |
| CN102276603A (zh) * | 2011-07-14 | 2011-12-14 | 福建省福抗药业股份有限公司 | 一种盐酸莫西沙星的清洁制备方法 |
| CN102952131A (zh) * | 2011-08-29 | 2013-03-06 | 成都国为医药科技有限公司 | 一种盐酸莫西沙星的制备方法 |
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| CN102603738A (zh) * | 2012-02-24 | 2012-07-25 | 天津市汉康医药生物技术有限公司 | 一种稳定的盐酸莫西沙星化合物 |
| CN102603738B (zh) * | 2012-02-24 | 2013-12-11 | 天津市汉康医药生物技术有限公司 | 一种稳定的盐酸莫西沙星化合物 |
| CN102924449A (zh) * | 2012-10-30 | 2013-02-13 | 重庆福安药业集团庆余堂制药有限公司 | 盐酸莫西沙星h晶型及其制备方法和药物组合物 |
| CN102924449B (zh) * | 2012-10-30 | 2015-08-12 | 重庆福安药业集团庆余堂制药有限公司 | 盐酸莫西沙星h晶型及其制备方法和药物组合物 |
| CN112759590A (zh) * | 2020-11-19 | 2021-05-07 | 内蒙古源宏精细化工有限公司 | 一种莫西沙星的制备方法 |
| CN115536658A (zh) * | 2022-09-09 | 2022-12-30 | 天方药业有限公司 | 一种盐酸莫西沙星一水合物制备方法 |
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