AU2006236423B2 - Pharmaceutical composition - Google Patents
Pharmaceutical composition Download PDFInfo
- Publication number
- AU2006236423B2 AU2006236423B2 AU2006236423A AU2006236423A AU2006236423B2 AU 2006236423 B2 AU2006236423 B2 AU 2006236423B2 AU 2006236423 A AU2006236423 A AU 2006236423A AU 2006236423 A AU2006236423 A AU 2006236423A AU 2006236423 B2 AU2006236423 B2 AU 2006236423B2
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- AU
- Australia
- Prior art keywords
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- methyl
- 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.)
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- 239000008194 pharmaceutical composition Substances 0.000 title description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 56
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 40
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 40
- 239000008203 oral pharmaceutical composition Substances 0.000 claims description 39
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 37
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 37
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 37
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 37
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 37
- 229940069328 povidone Drugs 0.000 claims description 37
- 229920003109 sodium starch glycolate Polymers 0.000 claims description 33
- 239000008109 sodium starch glycolate Substances 0.000 claims description 33
- 229940079832 sodium starch glycolate Drugs 0.000 claims description 33
- 235000019359 magnesium stearate Nutrition 0.000 claims description 28
- 150000004682 monohydrates Chemical class 0.000 claims description 24
- XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 239000003826 tablet Substances 0.000 description 101
- 239000000203 mixture Substances 0.000 description 100
- 150000001875 compounds Chemical class 0.000 description 71
- 239000008187 granular material Substances 0.000 description 69
- 239000004480 active ingredient Substances 0.000 description 67
- 239000007884 disintegrant Substances 0.000 description 50
- 239000011230 binding agent Substances 0.000 description 45
- 150000003839 salts Chemical class 0.000 description 45
- 238000007906 compression Methods 0.000 description 44
- 230000006835 compression Effects 0.000 description 44
- 239000003085 diluting agent Substances 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
- 239000000243 solution Substances 0.000 description 34
- 238000000034 method Methods 0.000 description 33
- 239000000314 lubricant Substances 0.000 description 31
- -1 (2-methanesulphonyl-ethylamino)-methyl Chemical group 0.000 description 27
- 239000007917 core tablet composition Substances 0.000 description 22
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- 239000012453 solvate Substances 0.000 description 19
- 102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 17
- 238000004090 dissolution Methods 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 16
- 238000005469 granulation Methods 0.000 description 16
- 230000003179 granulation Effects 0.000 description 16
- 229910052757 nitrogen Inorganic materials 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 208000035475 disorder Diseases 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- 102000001301 EGF receptor Human genes 0.000 description 11
- 108060006698 EGF receptor Proteins 0.000 description 11
- 230000001594 aberrant effect Effects 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- 239000008213 purified water Substances 0.000 description 11
- 238000002560 therapeutic procedure Methods 0.000 description 11
- 239000007864 aqueous solution Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 241000124008 Mammalia Species 0.000 description 8
- 238000011319 anticancer therapy Methods 0.000 description 8
- 201000011510 cancer Diseases 0.000 description 8
- 235000010980 cellulose Nutrition 0.000 description 8
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- 238000009501 film coating Methods 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 239000007916 tablet composition Substances 0.000 description 8
- 239000002246 antineoplastic agent Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000011248 coating agent Substances 0.000 description 7
- 238000000576 coating method Methods 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- UWYXLGUQQFPJRI-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine;4-methylbenzenesulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 UWYXLGUQQFPJRI-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000008186 active pharmaceutical agent Substances 0.000 description 6
- 229940088679 drug related substance Drugs 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 238000005029 sieve analysis Methods 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 229940034982 antineoplastic agent Drugs 0.000 description 5
- 230000022131 cell cycle Effects 0.000 description 5
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 5
- 229920000053 polysorbate 80 Polymers 0.000 description 5
- DRYRBWIFRVMRPV-UHFFFAOYSA-N quinazolin-4-amine Chemical class C1=CC=C2C(N)=NC=NC2=C1 DRYRBWIFRVMRPV-UHFFFAOYSA-N 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- FWMBEYDLDLJTDP-UHFFFAOYSA-N 2-iodoquinazoline Chemical compound C1=CC=CC2=NC(I)=NC=C21 FWMBEYDLDLJTDP-UHFFFAOYSA-N 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- HAZFJZBNKXYYNZ-UHFFFAOYSA-N O.S(=O)(=O)(O)C1=CC=C(C)C=C1.S(=O)(=O)(O)C1=CC=C(C)C=C1.CS(=O)(=O)CCNCC1=CC=C(O1)C1=NC2=CC=CC=C2C(=N1)N Chemical compound O.S(=O)(=O)(O)C1=CC=C(C)C=C1.S(=O)(=O)(O)C1=CC=C(C)C=C1.CS(=O)(=O)CCNCC1=CC=C(O1)C1=NC2=CC=CC=C2C(=N1)N HAZFJZBNKXYYNZ-UHFFFAOYSA-N 0.000 description 3
- 229920003110 Primojel Polymers 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- 108091008605 VEGF receptors Proteins 0.000 description 3
- 229940124650 anti-cancer therapies Drugs 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000000973 chemotherapeutic effect Effects 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- MTSNDBYBIZSILH-UHFFFAOYSA-N n-phenylquinazolin-4-amine Chemical class N=1C=NC2=CC=CC=C2C=1NC1=CC=CC=C1 MTSNDBYBIZSILH-UHFFFAOYSA-N 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 235000015424 sodium Nutrition 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
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- 229940032147 starch Drugs 0.000 description 3
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- 239000000126 substance Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-UHFFFAOYSA-N 2-(hydroxymethyl)-6-[4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol Chemical compound OCC1OC(OC2C(O)C(O)C(O)OC2CO)C(O)C(O)C1O GUBGYTABKSRVRQ-UHFFFAOYSA-N 0.000 description 2
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
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- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
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- 125000004546 quinazolin-4-yl group Chemical group N1=CN=C(C2=CC=CC=C12)* 0.000 description 2
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- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 2
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| JP5858989B2 (ja) | 2010-05-21 | 2016-02-10 | ノバルティス アーゲー | 組合せ |
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| PE20131341A1 (es) | 2010-08-03 | 2013-12-07 | Altherx Inc | Combinaciones de agonistas del receptor beta-3-adrenergico y antagonistas del receptor muscarinico para tratar vejiga hiperactiva |
| US9907767B2 (en) | 2010-08-03 | 2018-03-06 | Velicept Therapeutics, Inc. | Pharmaceutical compositions and the treatment of overactive bladder |
| EP2958552B1 (en) * | 2013-02-19 | 2017-06-21 | Hexal AG | Pharmaceutical composition comprising n-[3-chloro-4-(3-fluorobenzyloxy)phenyl]-6-[5({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]quinazolin-4-amine or a pharmaceutically acceptable salt, solvate or solvated salt thereof |
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| US9636340B2 (en) | 2013-11-12 | 2017-05-02 | Ayyappan K. Rajasekaran | Kinase inhibitors |
| MX2017007054A (es) | 2014-12-03 | 2018-05-02 | Velicept Therapeutics Inc | Composiciones y métodos para usar solabegron de liberación modificada para sintomas del tracto urinario inferior. |
| CN106389373B (zh) * | 2015-07-29 | 2019-07-02 | 四川科伦药物研究院有限公司 | 一种二甲苯磺酸拉帕替尼片剂及其制备方法 |
| CN106511289A (zh) * | 2015-09-10 | 2017-03-22 | 湖北生物医药产业技术研究院有限公司 | 甲苯磺酸拉帕替尼片剂及其制备方法 |
| CN108290824B (zh) | 2015-10-23 | 2022-03-11 | B3Ar治疗股份有限公司 | 索拉贝隆两性离子及其应用 |
| CA3149796A1 (en) | 2019-08-02 | 2021-02-11 | Onehealthcompany, Inc. | Anti-cancer agents for the treatment of canine cancers |
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| WO1999035146A1 (en) * | 1998-01-12 | 1999-07-15 | Glaxo Group Limited | Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors |
| WO2002002552A1 (en) * | 2000-06-30 | 2002-01-10 | Glaxo Group Limited | Quinazoline ditosylate salt compounds |
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| GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| US5760041A (en) | 1996-02-05 | 1998-06-02 | American Cyanamid Company | 4-aminoquinazoline EGFR Inhibitors |
| SK146199A3 (en) | 1997-04-25 | 2000-06-12 | Janssen Pharmaceutica Nv | Farnesyltransferase inhibiting quinazolinones |
| TW436485B (en) | 1997-08-01 | 2001-05-28 | American Cyanamid Co | Substituted quinazoline derivatives |
| US7141576B2 (en) | 2001-01-16 | 2006-11-28 | Smithkline Beecham (Cork) Limited | Cancer treatment method |
| AU2003221684A1 (en) | 2002-04-08 | 2003-10-27 | Smithkline Beecham Corporation | Cancer treatment method comprising administering an erb-family inhibitor and a raf and/or ras inhibitor |
| AU2003235470A1 (en) | 2002-06-19 | 2004-01-06 | Smithkline Beecham Corporation | Predictive markers in cancer therapy |
| KR101356748B1 (ko) * | 2005-04-19 | 2014-02-06 | 스미스클라인 비이참 (코르크) 리미티드 | 약제 조성물 |
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|---|---|---|---|---|
| WO1999035146A1 (en) * | 1998-01-12 | 1999-07-15 | Glaxo Group Limited | Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors |
| WO2002002552A1 (en) * | 2000-06-30 | 2002-01-10 | Glaxo Group Limited | Quinazoline ditosylate salt compounds |
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