ES2994850T3 - Crystallization process of aripiprazole derivatives in extended release formulations for treatment of schizophrenia - Google Patents
Crystallization process of aripiprazole derivatives in extended release formulations for treatment of schizophrenia Download PDFInfo
- Publication number
- ES2994850T3 ES2994850T3 ES21150116T ES21150116T ES2994850T3 ES 2994850 T3 ES2994850 T3 ES 2994850T3 ES 21150116 T ES21150116 T ES 21150116T ES 21150116 T ES21150116 T ES 21150116T ES 2994850 T3 ES2994850 T3 ES 2994850T3
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- ES
- Spain
- Prior art keywords
- temperature
- mixture
- formula
- aripiprazole
- compound
- 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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Links
- 238000000034 method Methods 0.000 title claims abstract description 134
- 230000008569 process Effects 0.000 title claims abstract description 89
- 239000000203 mixture Substances 0.000 title claims description 150
- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical class ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 title abstract description 41
- 238000002425 crystallisation Methods 0.000 title description 72
- 230000008025 crystallization Effects 0.000 title description 72
- 238000009472 formulation Methods 0.000 title description 10
- 201000000980 schizophrenia Diseases 0.000 title description 9
- 238000013265 extended release Methods 0.000 title description 5
- 239000002245 particle Substances 0.000 claims abstract description 134
- 239000013078 crystal Substances 0.000 claims abstract description 61
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 88
- 239000002904 solvent Substances 0.000 claims description 71
- 239000003814 drug Substances 0.000 claims description 62
- 229940079593 drug Drugs 0.000 claims description 61
- 150000001875 compounds Chemical class 0.000 claims description 60
- 238000001816 cooling Methods 0.000 claims description 59
- 238000000265 homogenisation Methods 0.000 claims description 51
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 32
- 229940011051 isopropyl acetate Drugs 0.000 claims description 32
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical group CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 16
- 239000012453 solvate Substances 0.000 claims description 16
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- DDINXHAORAAYAD-UHFFFAOYSA-N aripiprazole lauroxil Chemical compound C1=C2N(COC(=O)CCCCCCCCCCC)C(=O)CCC2=CC=C1OCCCCN(CC1)CCN1C1=CC=CC(Cl)=C1Cl DDINXHAORAAYAD-UHFFFAOYSA-N 0.000 description 99
- 229960003798 aripiprazole lauroxil Drugs 0.000 description 97
- 239000000243 solution Substances 0.000 description 70
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- 238000001953 recrystallisation Methods 0.000 description 42
- 230000000977 initiatory effect Effects 0.000 description 30
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 25
- 238000009826 distribution Methods 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 238000013400 design of experiment Methods 0.000 description 13
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 10
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 10
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 10
- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 10
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 10
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 10
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 10
- STDYTJDGBXCCRG-UHFFFAOYSA-N Aripiprazole cavoxil Chemical compound C1=C2N(COC(=O)CCCCC)C(=O)CCC2=CC=C1OCCCCN(CC1)CCN1C1=CC=CC(Cl)=C1Cl STDYTJDGBXCCRG-UHFFFAOYSA-N 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 8
- 238000004090 dissolution Methods 0.000 description 8
- 229940035044 sorbitan monolaurate Drugs 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
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- 229940088679 drug related substance Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000007972 injectable composition Substances 0.000 description 6
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 description 6
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 description 6
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 description 6
- 238000001556 precipitation Methods 0.000 description 6
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- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 5
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- 230000003190 augmentative effect Effects 0.000 description 5
- 229940043232 butyl acetate Drugs 0.000 description 5
- 229940093499 ethyl acetate Drugs 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 5
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 5
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 5
- 229940090181 propyl acetate Drugs 0.000 description 5
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 5
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- 230000002301 combined effect Effects 0.000 description 4
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- 238000012216 screening Methods 0.000 description 4
- 238000000527 sonication Methods 0.000 description 4
- 230000002269 spontaneous effect Effects 0.000 description 4
- 238000013268 sustained release Methods 0.000 description 4
- 239000012730 sustained-release form Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 239000013529 heat transfer fluid Substances 0.000 description 3
- 238000010255 intramuscular injection Methods 0.000 description 3
- 239000007927 intramuscular injection Substances 0.000 description 3
- 208000024714 major depressive disease Diseases 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 229940068977 polysorbate 20 Drugs 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
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- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
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- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
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- 208000020016 psychiatric disease Diseases 0.000 description 2
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- 238000007873 sieving Methods 0.000 description 2
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- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- RDYWTOWUSVAZGN-UHFFFAOYSA-N 7-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]-1-(hydroxymethyl)-3,4-dihydroquinolin-2-one Chemical compound C1=C2N(CO)C(=O)CCC2=CC=C1OCCCCN(CC1)CCN1C1=CC=CC(Cl)=C1Cl RDYWTOWUSVAZGN-UHFFFAOYSA-N 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
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- 206010022998 Irritability Diseases 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 229940056213 abilify Drugs 0.000 description 1
- 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 1
- 239000013543 active substance Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
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- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
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- 239000002464 receptor antagonist Substances 0.000 description 1
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Classifications
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462041341P | 2014-08-25 | 2014-08-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2994850T3 true ES2994850T3 (en) | 2025-02-03 |
Family
ID=55347322
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES21150116T Active ES2994850T3 (en) | 2014-08-25 | 2015-08-24 | Crystallization process of aripiprazole derivatives in extended release formulations for treatment of schizophrenia |
| ES15836431T Active ES2862098T3 (es) | 2014-08-25 | 2015-08-24 | Proceso de cristalización de derivados de aripiprazol en formulaciones de liberación prolongada para el tratamiento de la esquizofrenia |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES15836431T Active ES2862098T3 (es) | 2014-08-25 | 2015-08-24 | Proceso de cristalización de derivados de aripiprazol en formulaciones de liberación prolongada para el tratamiento de la esquizofrenia |
Country Status (20)
| Country | Link |
|---|---|
| US (5) | US10064859B2 (enExample) |
| EP (2) | EP3865476B1 (enExample) |
| JP (2) | JP6591546B2 (enExample) |
| CN (2) | CN111454207B (enExample) |
| AU (2) | AU2015306910B2 (enExample) |
| CA (1) | CA2959329C (enExample) |
| CY (1) | CY1124058T1 (enExample) |
| DK (1) | DK3185867T3 (enExample) |
| ES (2) | ES2994850T3 (enExample) |
| HR (1) | HRP20210551T1 (enExample) |
| HU (1) | HUE054641T2 (enExample) |
| IL (1) | IL250661B (enExample) |
| LT (1) | LT3185867T (enExample) |
| MA (2) | MA40480B1 (enExample) |
| PL (1) | PL3185867T3 (enExample) |
| PT (1) | PT3185867T (enExample) |
| RS (1) | RS61709B1 (enExample) |
| SI (1) | SI3185867T1 (enExample) |
| SM (1) | SMT202100212T1 (enExample) |
| WO (1) | WO2016032950A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ748572A (en) | 2012-09-19 | 2020-07-31 | Alkermes Pharma Ireland Ltd | Pharmaceutical compositions having improved storage stability |
| US10016415B2 (en) | 2014-08-18 | 2018-07-10 | Alkermes Pharma Ireland Limited | Aripiprazole prodrug compositions |
| PL3185867T3 (pl) * | 2014-08-25 | 2021-11-22 | Alkermes Pharma Ireland Limited | Sposób krystalizacji pochodnych arypiprazolu w formulacjach o przedłużonym uwalnianiu do leczenia schizofrenii |
| EP3294724A4 (en) * | 2015-05-08 | 2018-11-21 | Davuluri, Ramamohan Rao | Improved process for the preparation of aripiprazole with reduced particle size |
| WO2018104953A1 (en) * | 2016-12-07 | 2018-06-14 | Msn Laboratories Private Limited, R&D Center | Improved process for the preparation of 7-{4-[4-(2,3-dichlorophenyl)-piperazin-1-yl]butoxy}-2oxo-3,4-dihydro-2h-quinolin-1-yl)methyl dodecanoate |
| WO2019020821A1 (en) | 2017-07-28 | 2019-01-31 | Interquim, S.A. | PROCESS FOR THE PREPARATION OF LAUROXIL ARIPIPRAZOLE |
| CN110218209B (zh) * | 2018-03-02 | 2022-09-30 | 上海现代药物制剂工程研究中心有限公司 | 一种依匹哌唑月桂酸酯的晶型a、其制备方法及应用 |
| WO2019173230A1 (en) | 2018-03-05 | 2019-09-12 | Alkermes Pharma Ireland Limited | Aripiprazole dosing strategy |
| CN113105389B (zh) * | 2021-04-16 | 2022-04-08 | 江苏海洋大学 | 一种阿立哌唑药物共晶及其制备方法 |
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| CN1870980B (zh) * | 2003-10-23 | 2010-06-23 | 大冢制药株式会社 | 控释无菌阿立哌唑注射剂和方法 |
| CN105560176A (zh) | 2007-12-19 | 2016-05-11 | 詹森药业有限公司 | 与长效注射用帕潘立酮酯相关的给药方案 |
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| US8431576B2 (en) | 2009-06-25 | 2013-04-30 | Alkermes Pharma Ireland Limited | Heterocyclic compounds for the treatment of neurological and psychological disorders |
| WO2012077134A1 (en) * | 2010-12-07 | 2012-06-14 | Ind-Swift Laboratories Limted | Process for preparing aripiprazole polymorphs |
| MX345460B (es) * | 2011-01-07 | 2017-02-01 | Neodyne Biosciences Inc | Dispositivos y metodos para tratamiento de heridas o de la piel. |
| RS65237B1 (sr) * | 2011-03-18 | 2024-03-29 | Alkermes Pharma Ireland Ltd | Farmaceutske kompozicije koje sadrže sorbitan estre |
| US10004807B2 (en) * | 2012-03-19 | 2018-06-26 | Alkermes Pharma Ireland Limited | Pharmaceutical compositions comprising fatty acid esters |
| NZ748572A (en) * | 2012-09-19 | 2020-07-31 | Alkermes Pharma Ireland Ltd | Pharmaceutical compositions having improved storage stability |
| PL3185867T3 (pl) * | 2014-08-25 | 2021-11-22 | Alkermes Pharma Ireland Limited | Sposób krystalizacji pochodnych arypiprazolu w formulacjach o przedłużonym uwalnianiu do leczenia schizofrenii |
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