ES2562279T3 - Formulaciones de apixabán - Google Patents
Formulaciones de apixabán Download PDFInfo
- Publication number
- ES2562279T3 ES2562279T3 ES11707284.3T ES11707284T ES2562279T3 ES 2562279 T3 ES2562279 T3 ES 2562279T3 ES 11707284 T ES11707284 T ES 11707284T ES 2562279 T3 ES2562279 T3 ES 2562279T3
- Authority
- ES
- Spain
- Prior art keywords
- apixaban
- tablets
- particles
- dissolution
- apixabán
- 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.)
- Active
Links
- 239000000203 mixture Substances 0.000 title description 2
- 238000009472 formulation Methods 0.000 title 1
- QNZCBYKSOIHPEH-UHFFFAOYSA-N Apixaban Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)N(CC2)C=3C=CC(=CC=3)N3C(CCCC3)=O)=C2C(C(N)=O)=N1 QNZCBYKSOIHPEH-UHFFFAOYSA-N 0.000 abstract description 12
- 229960003886 apixaban Drugs 0.000 abstract description 12
- 239000002245 particle Substances 0.000 abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 abstract 2
- 239000002775 capsule Substances 0.000 abstract 1
- 239000003085 diluting agent Substances 0.000 abstract 1
- 238000002356 laser light scattering Methods 0.000 abstract 1
- 238000004090 dissolution Methods 0.000 description 8
- 238000005550 wet granulation Methods 0.000 description 7
- 238000007908 dry granulation Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 229960001681 croscarmellose sodium Drugs 0.000 description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
- 239000007888 film coating Substances 0.000 description 2
- 238000009501 film coating Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229940047623 apixaban 5 mg Drugs 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229960001021 lactose monohydrate Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4833—Encapsulating processes; Filling of capsules
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4162—1,2-Diazoles condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Polyurethanes Or Polyureas (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Un comprimido o una cápsula que comprenden una composición farmacéutica, en donde la composición farmacéutica comprende apixabán y un diluyente o un vehículo farmacéuticamente aceptables, en donde el apixabán está en forma de partículas y cristalina y las partículas individuales de apixabán, tanto si las partículas existen individualmente como si están aglomeradas, tienen un D90 igual a o menor de 89 μm medido por dispersión de luz láser.
Description
- Total
- 100,00 mg 400 mg
- Revestimiento de película
- 3,5 14,0
- Total
- 103,5 mg 414 mg
La Tabla 4 muestra las composiciones de los comprimidos de apixabán preparados usando el proceso de granulación en húmedo que se ha evaluado en un estudio de BE.
Tabla 4
- Ingredientes
- Granulación en húmedo
- 5 % p/p de fármaco cargado en la granulación (% p/p)
- 20 mg de comprimido (mg/comprimido)
- Intragranular
- Apixabán
- 5,00 20,00
- Lactosa monohidrato
- 70,0 280,00
- Celulosa microcristalina
- 5,00 60,00
- Croscarmelosa de sodio
- 2,50 10,00
- Povidona
- 4,50 18,00
- Agua purificada
- 17,40 69,60
- Extragranular
- Croscarmelosa de sodio
- 2,50 10,00
- Estearato de magnesio
- 0,50 2,09
- Celulosa microcristalina
- 10,00 10,09
- Total
- 100,00 400,00
- Revestimiento de película
- 3,5 14,0
- Total
- 103,5 mg 414,0
La Tabla 5 y la Tabla 5a muestran los datos de disolución que indican que tener un proceso de granulación en seco dará como resultado una disolución más rápida comparada con la de un proceso de granulación en húmedo. Como se muestra en la Tabla 5, los comprimidos de 20 mg fabricados usando un proceso de granulación en seco tenían
10 un 79 % de apixabán disuelto en 30 minutos frente al 62 % de apixabán disuelto a los 30 minutos para los comprimidos de 20 mg fabricados usando un proceso de granulación en húmedo. El ensayo de disolución en HCl 0,1 N también indicó un comportamiento similar de disolución más rápida de los comprimidos fabricados usando el proceso de granulación en seco (58 % en 30 min), comparado con el proceso de granulación en húmedo (45 % en 30 min).
15 Tabla 5
- Tiempo (minutos)
- % de apixabán disuelto (USP II, 75 rpm, SLS al 0,05 % en fosfato 50 mM, pH 6,8)
- Granulación en húmedo de comprimidos de 20 mg
- Granulación en seco de comprimidos de 20 mg
- 10
- 38 47
- 20
- 54 70
- 30
- 62 79
- 45
- 71 86
- 60
- 76 90
- Tamaño de partícula D90 (µm) del APT
- 83,8 83,8
Tabla 5a
- Tiempo (minutos)
- % de apixabán disuelto (USP II, 75 rpm, HCl 0,1 N)
- Granulación en húmedo de comprimidos de 20 mg
- Granulación en seco de comprimidos de 20 mg
- 10
- 30 41
7
Las Figuras 3 y 4 ilustran los datos de disolución que muestran que mientras que el tamaño de partícula afecta a la disolución, controlar el tamaño de partícula a menos de 89 micrómetros dará como resultado una velocidad de disolución que asegurará las exposiciones in vivo consistentes. Como se ha indicado en las Figuras 3 y 4, se esperan exposiciones consistentes cuando los comprimidos de apixabán tengan más del 77 % de apixabán disuelto 5 en 30 minutos. Dado que los comprimidos con 89 micrómetros tienen > 77 % disuelto a los 30 minutos, estos comprimidos también exhibirán exposiciones que son equivalentes a las exposiciones de los comprimidos fabricados con partículas más pequeñas (tales como los comprimidos con partículas de 10 micrómetros mostrados a continuación). Mientras que la velocidad de disolución a un tamaño de partícula de apixabán de 119 micrómetros es ligeramente mayor del 77 % en 30 min para los comprimidos de 5 mg de apixabán (Figura 4), el umbral del tamaño
10 de partícula reivindicado es de menos de 89 micrómetros. Esto permite la variabilidad típica (RSD = 2 a 3 %) en los resultados de disolución, de manera que la biodisponibilidad oral de los comprimidos coincida consistentemente con la de la solución.
9
Claims (1)
-
imagen1 imagen2
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30805610P | 2010-02-25 | 2010-02-25 | |
| US308056P | 2010-02-25 | ||
| PCT/US2011/025994 WO2011106478A2 (en) | 2010-02-25 | 2011-02-24 | Apixaban formulations |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2562279T3 true ES2562279T3 (es) | 2016-03-03 |
Family
ID=43901603
Family Applications (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17178613T Active ES2757603T3 (es) | 2010-02-25 | 2011-02-24 | Formulaciones de apixabán |
| ES15190823T Active ES2714363T3 (es) | 2010-02-25 | 2011-02-24 | Formulaciones de apixabán |
| ES17175864T Active ES2767848T3 (es) | 2010-02-25 | 2011-02-24 | Formulaciones de apixabán |
| ES11707284.3T Active ES2562279T3 (es) | 2010-02-25 | 2011-02-24 | Formulaciones de apixabán |
| ES17175788T Active ES2758031T3 (es) | 2010-02-25 | 2011-02-24 | Formulaciones de apixabán |
Family Applications Before (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17178613T Active ES2757603T3 (es) | 2010-02-25 | 2011-02-24 | Formulaciones de apixabán |
| ES15190823T Active ES2714363T3 (es) | 2010-02-25 | 2011-02-24 | Formulaciones de apixabán |
| ES17175864T Active ES2767848T3 (es) | 2010-02-25 | 2011-02-24 | Formulaciones de apixabán |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17175788T Active ES2758031T3 (es) | 2010-02-25 | 2011-02-24 | Formulaciones de apixabán |
Country Status (31)
| Country | Link |
|---|---|
| US (5) | US9326945B2 (es) |
| EP (7) | EP3662899A1 (es) |
| JP (4) | JP5846647B2 (es) |
| KR (4) | KR20210124532A (es) |
| CN (3) | CN109602713A (es) |
| AU (1) | AU2011220775B2 (es) |
| BR (1) | BR112012021337A8 (es) |
| CA (1) | CA2791171C (es) |
| CO (1) | CO6640207A2 (es) |
| CY (5) | CY1117434T1 (es) |
| DK (5) | DK3017811T3 (es) |
| ES (5) | ES2757603T3 (es) |
| HK (2) | HK1243947B (es) |
| HR (5) | HRP20160179T1 (es) |
| HU (4) | HUE047140T2 (es) |
| IL (3) | IL309564A (es) |
| IN (1) | IN2012DN06587A (es) |
| LT (4) | LT3251660T (es) |
| MX (3) | MX364938B (es) |
| NZ (1) | NZ601738A (es) |
| PE (3) | PE20160042A1 (es) |
| PL (5) | PL3246021T3 (es) |
| PT (5) | PT3246021T (es) |
| RS (5) | RS54559B1 (es) |
| RU (1) | RU2685724C2 (es) |
| SG (2) | SG10201501349VA (es) |
| SI (5) | SI3246021T1 (es) |
| SM (5) | SMT201900212T1 (es) |
| TR (1) | TR201903195T4 (es) |
| WO (1) | WO2011106478A2 (es) |
| ZA (1) | ZA201205807B (es) |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210124532A (ko) * | 2010-02-25 | 2021-10-14 | 브리스톨-마이어스 스퀴브 홀딩스 아일랜드 언리미티드 컴퍼니 | 아픽사반 제제 |
| WO2013164839A2 (en) * | 2012-03-06 | 2013-11-07 | Cadila Healthcare Limited | Amorphous form of apixaban, process of preparation and compositions thereof |
| EP2854759B1 (en) * | 2012-05-24 | 2019-12-18 | ratiopharm GmbH | Dosage forms comprising apixaban and matrix former |
| EP2900217A1 (en) * | 2012-09-26 | 2015-08-05 | Bristol-Myers Squibb Company | Apixaban liquid formulations |
| CN102908324A (zh) * | 2012-10-31 | 2013-02-06 | 南京正科制药有限公司 | 一种阿哌沙班片 |
| EP2752414A1 (en) | 2013-01-04 | 2014-07-09 | Sandoz AG | Crystalline form of apixaban |
| CZ2013305A3 (cs) | 2013-04-23 | 2014-11-05 | Zentiva, K.S. | Nové krystalické formy APIXABANU a způsob jejich přípravy |
| US20160113912A1 (en) * | 2013-06-18 | 2016-04-28 | Cadila Healthcare Limited | An improved process for the preparation of apixaban and intermediates thereof |
| EP2907507A1 (en) | 2014-02-17 | 2015-08-19 | Sandoz Ag | Pharmaceutical composition comprising apixaban |
| CN103830199A (zh) * | 2014-03-24 | 2014-06-04 | 重庆东得医药科技有限公司 | 含阿哌沙班的药用制剂及其制备方法 |
| DK3172209T3 (da) | 2014-07-25 | 2021-02-22 | Novartis Ag | Tabletformulering med 2-fluor-n-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamid |
| CN104316637B (zh) * | 2014-10-30 | 2016-08-17 | 江苏宝众宝达药业有限公司 | 高效液相色谱法测定阿哌沙班清洗残留量 |
| US9603846B2 (en) | 2014-11-25 | 2017-03-28 | Cadila Healthcare Limited | Process for the preparation of apixaban |
| WO2016181276A1 (en) * | 2015-05-08 | 2016-11-17 | Wockhardt Limited | Stable pharmaceutical compositions comprising antibacterial agent |
| WO2017088841A1 (en) | 2015-11-26 | 2017-06-01 | Zentiva, K.S. | Preparation of a drug form containing amorphous apixaban |
| CN106913528A (zh) * | 2015-12-25 | 2017-07-04 | 中美华世通生物医药科技（武汉）有限公司 | 阿哌沙班微丸及其制备方法 |
| US10537524B2 (en) | 2016-01-12 | 2020-01-21 | North & South Brother Pharmacy Investment Company Limited | Apixaban solid composition and preparation method thereof |
| EP3195860A1 (de) * | 2016-01-22 | 2017-07-26 | STADA Arzneimittel AG | Verfahren zur herstellung eines apixaban-granulates |
| WO2017163170A1 (en) * | 2016-03-21 | 2017-09-28 | Sun Pharmaceutical Industries Limited | Pharmaceutical composition comprising apixaban |
| WO2017182908A1 (en) * | 2016-04-18 | 2017-10-26 | Emcure Pharmaceuticals Limited | Pharmaceutical compositions of apixaban |
| EP3243505A1 (en) | 2016-05-13 | 2017-11-15 | Zaklady Farmaceutyczne Polpharma SA | A pharmaceutical composition comprising amorphous apixaban |
| CN106822006B (zh) * | 2016-06-08 | 2020-08-28 | 北京普德康利医药科技发展有限公司 | 一种阿哌沙班片及其制备方法 |
| WO2017221209A1 (en) | 2016-06-23 | 2017-12-28 | Lupin Limited | Pharmaceutical formulations of apixaban |
| UA123464C2 (uk) * | 2016-09-24 | 2021-04-07 | Кейбіпі Байосайєнсіз Ко., Лтд. | Фармацевтична композиція, яка містить антагоніст мінералокортикоїдних рецепторів, та її застосування |
| CN106420651B (zh) * | 2016-09-28 | 2019-03-08 | 乐普药业股份有限公司 | 一种阿哌沙班片的制备方法 |
| EP3582777A4 (en) | 2017-02-17 | 2020-12-23 | Unichem Laboratories Ltd | PHARMACEUTICAL COMPOSITION OF APIXABAN |
| JP7044115B2 (ja) | 2017-11-27 | 2022-03-30 | 三菱ケミカル株式会社 | ゴム含有グラフト重合体組成物を含む熱可塑性樹脂の樹脂改質用組成物、ゴム含有グラフト重合体含有樹脂組成物およびその成形体 |
| KR20190075566A (ko) | 2017-12-21 | 2019-07-01 | 전자부품연구원 | 다중 센서를 활용한 용변 습관 모니터링 시스템 및 방법 |
| TR201722523A2 (tr) | 2017-12-28 | 2019-07-22 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Api̇ksaban i̇çeren kati oral farmasöti̇k kompozi̇syonlar |
| CN108236604A (zh) * | 2018-02-07 | 2018-07-03 | 中国药科大学 | 阿哌沙班柔性脂质体 |
| PL3781132T3 (pl) | 2018-04-16 | 2024-05-20 | Bristol-Myers Squibb Company | Preparaty apiksabanu |
| KR20190130411A (ko) | 2018-05-14 | 2019-11-22 | 신일제약주식회사 | 아픽사반 약제학적 제제 및 그의 제조방법 |
| CA3109007A1 (en) | 2018-08-14 | 2020-02-20 | Jiangsu Hengrui Medicine Co., Ltd. | Injectable pharmaceutical composition and preparation method therefor |
| EP3666773A1 (en) | 2018-12-11 | 2020-06-17 | KRKA, D.D., Novo Mesto | Process for preparing apixaban |
| EP3669866A1 (en) | 2018-12-19 | 2020-06-24 | KRKA, d.d., Novo mesto | Pharmaceutical composition comprising apixaban |
| CN111377915B (zh) * | 2018-12-30 | 2023-10-24 | 鲁南制药集团股份有限公司 | 一种吡唑并-吡啶酮化合物晶型d |
| CN109464415B (zh) * | 2019-01-09 | 2021-08-17 | 常州恒邦药业有限公司 | 阿哌沙班药物组合物及其制备方法 |
| AU2020384737A1 (en) | 2019-11-13 | 2022-05-26 | Unison Pharmaceuticals Pvt. Ltd. | Orally disintegrating pharmaceutical compositions of apixaban |
| CN111214442B (zh) * | 2020-02-13 | 2021-12-10 | 山东百诺医药股份有限公司 | 一种阿哌沙班共微粉化物 |
| CN111494326A (zh) * | 2020-04-11 | 2020-08-07 | 南京正大天晴制药有限公司 | 一种阿哌沙班片及其制备方法 |
| WO2022115052A1 (en) | 2020-11-27 | 2022-06-02 | Santa Farma Ilac Sanayii A.S. | Improved wet granulation processes for apixaban comprising formulations |
| WO2022115051A1 (en) | 2020-11-27 | 2022-06-02 | Santa Farma Ilac Sanayii A.S. | Direct compression method for non-micronised apixaban formulations |
| TR202100250A2 (tr) | 2021-01-08 | 2022-07-21 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Api̇ksaban i̇çeren fi̇lm kapli tablet |
| WO2022150030A2 (en) | 2021-01-08 | 2022-07-14 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | A film coated tablet of apixaban |
| JP2022112698A (ja) * | 2021-01-22 | 2022-08-03 | 東和薬品株式会社 | アピキサバン含有医薬組成物 |
| GB202102575D0 (en) | 2021-02-23 | 2021-04-07 | Teva Pharmaceutical Industries Ltd | Fixed-dose pharmaceutical compositions |
| PH12023553262A1 (en) * | 2021-06-08 | 2024-03-25 | Taho Pharmaceuticals Ltd | Apixaban film product and uses thereof |
| EP4412586A1 (en) | 2021-10-27 | 2024-08-14 | Pharma-Data S.A. | Apixaban suspension and preparation method |
| JP2024057549A (ja) * | 2022-10-12 | 2024-04-24 | 日本ジェネリック株式会社 | アピキサバンを含有する錠剤 |
| KR102760108B1 (ko) | 2024-04-09 | 2025-01-24 | 에바바이오 주식회사 | 수용해도와 투과도를 향상시켜 생체이용률이 개선된 무정형 아픽사반 고체분산체 제제 및 그의 서방성 정제 |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6150366A (en) | 1998-06-15 | 2000-11-21 | Pfizer Inc. | Ziprasidone formulations |
| NZ511674A (en) | 1998-12-23 | 2003-11-28 | Du Pont Pharm Co | Nitrogen containing heterobicycles as factor Xa inhibitors |
| AU2002341693B2 (en) | 2001-09-21 | 2008-05-29 | Bristol-Myers Squibb Holdings Ireland Unlimited Company | Lactam-containing compounds and derivatives thereof as factor Xa inhibitors |
| TWI331526B (en) | 2001-09-21 | 2010-10-11 | Bristol Myers Squibb Pharma Co | Lactam-containing compounds and derivatives thereof as factor xa inhibitors |
| US20070025991A1 (en) * | 2003-03-19 | 2007-02-01 | Charalabos Pothoulakis | Use of antagonists of ghrelin or ghrelin receptor to treat intestinal inflammation |
| US20050059719A1 (en) * | 2003-09-16 | 2005-03-17 | Badawy Sherif Ibrahim Farag | Solid dosage formulation containing a Factor Xa inhibitor and method |
| DE10355461A1 (de) * | 2003-11-27 | 2005-06-23 | Bayer Healthcare Ag | Verfahren zur Herstellung einer festen, oral applizierbaren pharmazeutischen Zusammensetzung |
| US7434502B2 (en) | 2004-07-21 | 2008-10-14 | Husqvarna Outdoor Products Inc. | Bar knob with cam-operated locking mechanism |
| US20060016084A1 (en) * | 2004-07-24 | 2006-01-26 | Ching-Lin Liao | Laser-Based datum instrument |
| US7396932B2 (en) * | 2004-09-28 | 2008-07-08 | Bristol-Myers Squibb Company | Process for preparing 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones |
| US20060160841A1 (en) * | 2005-01-19 | 2006-07-20 | Chenkou Wei | Crystallization via high-shear transformation |
| GB0507577D0 (en) * | 2005-04-14 | 2005-05-18 | Novartis Ag | Organic compounds |
| US20070191306A1 (en) * | 2005-08-17 | 2007-08-16 | Bristol-Myers Squibb Company | FACTOR Xa INHIBITOR FORMULATION AND METHOD |
| WO2007053904A1 (en) | 2005-11-10 | 2007-05-18 | Alphapharm Pty Ltd | Process to control particle size |
| US20070259913A1 (en) | 2006-05-04 | 2007-11-08 | David Deitchman | Prophylaxis of thromboembolic events in cancer patients |
| PE20080661A1 (es) * | 2006-09-12 | 2008-06-12 | Glaxo Group Ltd | COMPOSICION FARMACEUTICA QUE COMPRENDE UN INHIBIDOR DEL FACTOR Xa |
| FI20080351A0 (fi) | 2008-05-09 | 2008-05-09 | Atacama Labs Oy | Prosessi matalan lääkepitoisuuden tabletin valmistamiseksi |
| CN101686959B (zh) * | 2007-05-02 | 2014-05-07 | 波托拉医药品公司 | 作为血小板adp受体抑制剂的化合物的组合疗法 |
| US9050368B2 (en) * | 2007-11-13 | 2015-06-09 | Meritage Pharma, Inc. | Corticosteroid compositions |
| EP2291233B1 (en) * | 2008-05-09 | 2019-09-04 | Atacama Labs Oy | Method for dry granulation |
| CN102089051A (zh) | 2008-07-11 | 2011-06-08 | 巴斯夫欧洲公司 | 作为形态学改变剂的两亲性蛋白质 |
| US20100018486A1 (en) * | 2008-07-22 | 2010-01-28 | Hung-Tao Liu | Cathode energy fuel-saving device |
| NZ720946A (en) * | 2009-04-29 | 2017-09-29 | Amarin Pharmaceuticals Ie Ltd | Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same |
| SMT202000093T1 (it) | 2009-06-16 | 2020-03-13 | Pfizer | Forme di dosaggio di apixaban |
| KR20210124532A (ko) | 2010-02-25 | 2021-10-14 | 브리스톨-마이어스 스퀴브 홀딩스 아일랜드 언리미티드 컴퍼니 | 아픽사반 제제 |
| AU2011225810B2 (en) * | 2010-03-10 | 2014-11-06 | Lupin Limited | Rifaximin ready-to-use suspension |
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