JP5192568B2 - エスシタロプラムを含む結晶性組成物 - Google Patents
エスシタロプラムを含む結晶性組成物 Download PDFInfo
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- JP5192568B2 JP5192568B2 JP2011120483A JP2011120483A JP5192568B2 JP 5192568 B2 JP5192568 B2 JP 5192568B2 JP 2011120483 A JP2011120483 A JP 2011120483A JP 2011120483 A JP2011120483 A JP 2011120483A JP 5192568 B2 JP5192568 B2 JP 5192568B2
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- Japan
- Prior art keywords
- pharmaceutical composition
- composition according
- escitalopram
- filler
- escitalopram oxalate
- 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.)
- Expired - Lifetime
Links
- 229960004341 escitalopram Drugs 0.000 title claims description 21
- WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 title claims description 21
- 239000000203 mixture Substances 0.000 title description 19
- 239000002245 particle Substances 0.000 claims description 57
- KTGRHKOEFSJQNS-BDQAORGHSA-N (1s)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3h-2-benzofuran-5-carbonitrile;oxalic acid Chemical compound OC(=O)C(O)=O.C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 KTGRHKOEFSJQNS-BDQAORGHSA-N 0.000 claims description 42
- 229960005086 escitalopram oxalate Drugs 0.000 claims description 42
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 239000000945 filler Substances 0.000 claims description 14
- 239000004480 active ingredient Substances 0.000 claims description 11
- 235000019359 magnesium stearate Nutrition 0.000 claims description 11
- 239000011230 binding agent Substances 0.000 claims description 10
- 238000007907 direct compression Methods 0.000 claims description 10
- 239000000314 lubricant Substances 0.000 claims description 10
- 239000000454 talc Substances 0.000 claims description 10
- 229910052623 talc Inorganic materials 0.000 claims description 10
- 235000012222 talc Nutrition 0.000 claims description 10
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 7
- 239000008101 lactose Substances 0.000 claims description 7
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 6
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 6
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical class [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 6
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 6
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 6
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 6
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 6
- 229920000881 Modified starch Polymers 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- 239000001506 calcium phosphate Substances 0.000 claims description 4
- 235000011010 calcium phosphates Nutrition 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound 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 GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 3
- 101000945318 Homo sapiens Calponin-1 Proteins 0.000 claims description 3
- 101000652736 Homo sapiens Transgelin Proteins 0.000 claims description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- 239000004368 Modified starch Substances 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 235000021355 Stearic acid Nutrition 0.000 claims description 3
- 102100031013 Transgelin Human genes 0.000 claims description 3
- 239000011575 calcium Substances 0.000 claims description 3
- 229910052791 calcium Inorganic materials 0.000 claims description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 3
- 239000008116 calcium stearate Substances 0.000 claims description 3
- 235000013539 calcium stearate Nutrition 0.000 claims description 3
- 239000008119 colloidal silica Substances 0.000 claims description 3
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims description 3
- 229910052749 magnesium Inorganic materials 0.000 claims description 3
- 239000011777 magnesium Substances 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 235000019426 modified starch Nutrition 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 3
- 239000008117 stearic acid Substances 0.000 claims description 3
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 claims description 3
- 239000001993 wax Substances 0.000 claims description 3
- 235000011132 calcium sulphate Nutrition 0.000 claims description 2
- 150000001720 carbohydrates Chemical class 0.000 claims description 2
- 159000000000 sodium salts Chemical class 0.000 claims 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 claims 1
- 229960001681 croscarmellose sodium Drugs 0.000 claims 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims 1
- 238000000034 method Methods 0.000 description 31
- 238000001816 cooling Methods 0.000 description 26
- 239000007892 solid unit dosage form Substances 0.000 description 24
- 239000003826 tablet Substances 0.000 description 21
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 239000013078 crystal Substances 0.000 description 12
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 11
- 229960001653 citalopram Drugs 0.000 description 11
- 238000002425 crystallisation Methods 0.000 description 11
- 239000000546 pharmaceutical excipient Substances 0.000 description 11
- 230000008025 crystallization Effects 0.000 description 10
- 238000005469 granulation Methods 0.000 description 10
- 230000003179 granulation Effects 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 9
- 239000007787 solid Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- WIHMBLDNRMIGDW-UHFFFAOYSA-N 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3h-2-benzofuran-5-carbonitrile;hydron;bromide Chemical compound [Br-].O1CC2=CC(C#N)=CC=C2C1(CCC[NH+](C)C)C1=CC=C(F)C=C1 WIHMBLDNRMIGDW-UHFFFAOYSA-N 0.000 description 6
- 229960000584 citalopram hydrobromide Drugs 0.000 description 6
- 238000009826 distribution Methods 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 238000011049 filling Methods 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 239000002775 capsule Substances 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 235000006408 oxalic acid Nutrition 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 230000001430 anti-depressive effect Effects 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 238000010899 nucleation Methods 0.000 description 3
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 3
- 229940032147 starch Drugs 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000004135 Bone phosphate Substances 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 229960005168 croscarmellose Drugs 0.000 description 2
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000007909 melt granulation Methods 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 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 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 229940095672 calcium sulfate Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-M oxalate(1-) Chemical compound OC(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-M 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- -1 preferably dibasic Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
- 238000010977 unit operation Methods 0.000 description 1
- 239000000080 wetting agent Substances 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
-
- 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
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Cephalosporin Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
エスシタロプラム及びシュウ酸の各エタノール溶液を混合することによって粗製エスシタロプラムシュウ酸塩を析出させて得られた、エスシタロプラムシュウ酸塩を約35kg含む含湿フィルターケーキを、エタノール322L中に懸濁させた。この材料を、還流温度に加熱することによって溶解し、そして蒸留して150Lのエタノールを除去した。冷却を行い、80℃から40℃に至るまでの温度間隔において0.2〜0.5℃/分の冷却速度を用いて上記混合物を還流温度から15℃に冷却した。冷却中、75℃、65℃及び60℃の温度の時にこの混合物をエスシタロプラムシュウ酸塩で種付けした(各々、10g加えた)。この結晶化混合物は、結晶性エスシタロプラムシュウ酸塩が単離されるまで、10時間15℃に維持した。この結晶化混合物を濾過し、エタノールで洗浄し、そしてフィルターケーキを乾燥することによって、精製されたエスシタロプラムシュウ酸塩(27.7kg、理論値の58.2%)が得られた。得られたエスシタロプラムシュウ酸塩の粒度分布を表1に示す。
エスシタロプラムシュウ酸塩の大きな結晶性粒子を直接圧縮することによって製造した錠剤
×8mmパンチを備えたコルシュ(Korsch)PH230打錠機で錠剤化した(1時
間当たり125,000錠)。錠剤心材の重量は125mgに設定した。公称収量は20
0,000錠であった。打錠機は、混合物の高さが強制供給装置を超えるまで運転した。
すなわち、最終量の混合物において起こりうる分離傾向を確認するために錠剤化をできる
だけ長く続けた。製造された錠剤は満足な技術的性質を有していた。
本願は、特許請求の範囲に記載の発明に関するものであるが、他の態様として以下も包
含し得る。
1.結晶のメジアン粒径が少なくとも40μmであることを特徴とする、エスシタロプラ
ムシュウ酸塩の結晶性粒子。
2.結晶のメジアン粒径が50〜200μmの範囲であることを特徴とする、上記1の結
晶性粒子。
3.適当な溶剤系中のエスシタロプラムシュウ酸塩の溶液を第一の温度から第二の温度ま
で徐冷し、この際、この冷却は、制御された冷却プロフィルを維持し、なおかつ上記冷却
の間にエスシタロプラムシュウ酸塩の結晶を加えることによってエスシタロプラムシュウ
酸塩の上記溶液を種付けしながら行い、その後、上記の第二の温度での保持時間がこれに
続くことを含むことを特徴とする、上記1または2に記載のエスシタロプラムシュウ酸塩
の結晶性粒子の製造方法。
4.結晶のメジアン粒径が少なくとも40μm、好ましくは50〜200μmの範囲であ
ることを特徴とする、上記3の方法。
5.溶剤系が一種または二種以上のアルコール及び場合によっては水を含むことを特徴と
する、上記3または4の方法。
6.溶剤系がエタノールであることを特徴とする、上記5の方法。
7.溶質:溶剤の重量比が、0.05:1〜0.6:1、好ましくは0.1:1〜0.5
:1、より好ましくは0.2:1〜0.4:1であることを特徴とする、上記3〜6のい
ずれか一つの方法。
8.上記の第一の温度が50℃〜溶剤系の還流温度の範囲、好ましくは60℃〜還流温度
の範囲、より好ましくは70℃〜還流温度の範囲であることを特徴とする、上記3〜7の
いずれか一つの方法。
9.上記の第二の温度が0〜20℃、好ましくは0〜15℃、より好ましくは7〜15℃
の範囲であることを特徴とする、上記3〜8のいずれか一つの方法。
10.上記の制御された冷却プロフィルが初期冷却期間を含み、この間、冷却速度を所定
の範囲内に維持することを特徴とする、上記3〜9のいずれか一つの方法。
11.上記の初期冷却期間が、温度が60℃未満、好ましくは50℃未満、より好ましく
は40℃未満になるまでの期間に及ぶことを特徴とする、上記10の方法。
12.上記の冷却速度が、0〜0.6℃/分、好ましくは0.2〜0.4℃/分の範囲に
維持されることを特徴とする、上記10または11の方法。
13.上記の種付けが、初期冷却の間に二度または三度以上行われることを特徴とする、
上記3〜12のいずれか一つの方法。
14.上記の保持時間が、少なくとも1時間、好ましくは4〜24時間、より好ましくは
6〜12時間であることを特徴とする、上記3〜13のいずれか一つの方法。
15.上記の保持時間の後の結晶性粒子を、慣用の固形物/液体分離技術、好ましくは濾
過によって母液から単離する、上記3〜14のいずれか一つの方法。
16.上記1または2のエスシタロプラムシュウ酸塩の結晶性粒子を含む、固形単位投薬
形。
17.エスシタロプラムシュウ酸塩と薬学的に許容可能な賦形剤とを含む混合物を直接圧
縮することによって製造される錠剤であることを特徴とする、上記16の固形単位投薬形
。
18.タブレットがコーティングされていることを特徴とする、上記17の固形単位投薬
形。
19.エスシタロプラムシュウ酸塩と薬学的に許容可能な賦形剤とを含む混合物を硬質の
ゼラチンカプセル内に充填することによって製造されることを特徴とする、上記16の固
形単位投薬形。
20.バインダーを含まないことを特徴とする、上記16〜19のいずれか一つの固形単
位投薬形。
21.エスシタロプラム塩基として計算して有効成分を1〜30%w/w、好ましくは4
〜20%w/w、より好ましくは6〜10%w/wの割合で含むことを特徴とする、上記
16〜20のいずれか一つの固形単位投薬形。
22.ラクトース、糖類、好ましくはソルビトール、マンニトール、デキストロース及び
/またはスクロース、リン酸カルシウム類、好ましくは二塩基性、三塩基性、含水及び/
または無水リン酸カルシウム、デンプン、加工デンプン、微結晶性セルロース、硫酸カル
シウム及び/または炭酸カルシウムから選択されるフィラーを含むことを特徴とする、上
記16〜21のいずれか一つの固形単位投薬形。
23.フィラーが微結晶性セルロース、例えばProSolv SMCC90またはAv
icel PH 200であることを特徴とする、上記22の固形単位投薬形。
24.ステアリン酸金属塩(マグネシウム、カルシウム、ナトリウム塩)、ステアリン酸
、ワックス、水素化された植物油、タルク及びコロイダルシリカから選択される潤滑剤を
含むことを特徴とする、上記16〜23のいずれか一つの固形単位投薬形。
25.潤滑剤が、タルク、ステアリン酸マグネシウム及びステアリン酸カルシウムの群か
ら選択される一種または二種以上のものであることを特徴とする、上記24の固形単位投
薬形。
26.潤滑剤が、タルクとステアリン酸マグネシウムとの組み合わせであることを特徴と
する、上記25の固形単位投薬形。
27.固形投与形態の重量に基づいて計算してステアリン酸マグネシウムの重量%が、好
ましくは0.4%〜2%の範囲、より好ましくは0.7%〜1.4%の範囲であることを
特徴とする、上記26の固形単位投薬形。
28.ラクトースを実質的に含まないことを特徴とする、上記16〜27のいずれか一つ
の固形単位投薬形。
Claims (11)
- エスシタロプラムシュウ酸塩の結晶性粒子、及びフィラーを含む医薬組成物であって、前記医薬組成物が、直接圧縮することによって製造される錠剤であり、エスシタロプラムシュウ酸塩の結晶性粒子のメジアン粒径が、50〜200μmであるとともに前記フィラーのメジアン粒径と同じくらいであり、前記フィラーが、ProSolv SMCC90(登録商標)として特定される微結晶性セルロースであることを特徴とする、医薬組成物。
- 前記錠剤がコーティングされていることを特徴とする、請求項1に記載の医薬組成物。
- バインダーを含まないことを特徴とする、請求項1〜2のいずれかに記載の医薬組成物。
- エスシタロプラム塩基として計算して有効成分を1〜30%w/wの割合で含むことを特徴とする、請求項1〜3のいずれかに記載の医薬組成物。
- ラクトース、糖類、リン酸カルシウム類、デンプン、加工デンプン、硫酸カルシウム及び/または炭酸カルシウムから選択されるフィラーをさらに含むことを特徴とする、請求項1〜4のいずれかに記載の医薬組成物。
- ステアリン酸金属塩(マグネシウム、カルシウム、ナトリウム塩)、ステアリン酸、ワックス、水素化された植物油、タルク及びコロイダルシリカから選択される潤滑剤を含むことを特徴とする、請求項1〜5のいずれかに記載の医薬組成物。
- 潤滑剤が、タルク、ステアリン酸マグネシウム及びステアリン酸カルシウムの群から選択される一種または二種以上のものであることを特徴とする、請求項6に記載の医薬組成物。
- 潤滑剤が、タルクとステアリン酸マグネシウムとの組み合わせであることを特徴とする、請求項7に記載の医薬組成物。
- 医薬組成物の重量に基づいて計算してステアリン酸マグネシウムの重量%が、0.4%〜2%の範囲であることを特徴とする、請求項8に記載の医薬組成物。
- ラクトースを含まないことを特徴とする、請求項1〜9のいずれかに記載の医薬組成物。
- エスシタロプラムシュウ酸塩の結晶性粒子10.2重量%、ProSolv SMCC90(登録商標)として特定される微結晶性セルロースであるフィラー79.6重量%、Ac-Di-Sol(登録商標)として特定されるクロスカルメロースナトリウム3.6重量%及びステアリン酸マグネシウム1.0重量%を含む錠剤心材を含む、請求項1に記載の医薬組成物。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2012211186A (ja) * | 2001-07-31 | 2012-11-01 | H Lundbeck As | エスシタロプラムを含む結晶性組成物 |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE237604T1 (de) | 1999-04-14 | 2003-05-15 | Lundbeck & Co As H | Verfahren zur herstellung von citalopram |
US20030232881A1 (en) * | 2000-10-27 | 2003-12-18 | H. Lundbeck A/S | Crystals of pharmaceutically acceptable salts of citalopram, methods of crystallization, and pharmaceutical compositions comprising them |
US20030109577A1 (en) * | 2000-10-27 | 2003-06-12 | Ken Liljegren | Pharmaceutical composition containing citalopram |
PE20040991A1 (es) | 2002-08-12 | 2004-12-27 | Lundbeck & Co As H | Separacion de intermediarios para la preparacion de escitalopram |
AU2003223105A1 (en) * | 2003-03-24 | 2004-10-18 | Hetero Drugs Limited | Novel crystalline forms of (s)-citalopram oxalate |
US20040265375A1 (en) * | 2003-04-16 | 2004-12-30 | Platteeuw Johannes J. | Orally disintegrating tablets |
TWI339651B (en) * | 2004-02-12 | 2011-04-01 | Lundbeck & Co As H | Method for the separation of intermediates which may be used for the preparation of escitalopram |
CA2558198A1 (en) * | 2004-03-05 | 2005-09-15 | H. Lundbeck A/S | Crystalline composition containing escitalopram oxalate |
US20050196453A1 (en) * | 2004-03-05 | 2005-09-08 | H. Lundbeck A/S | Crystalline composition containing escitalopram |
EP1901714A2 (en) * | 2005-05-20 | 2008-03-26 | Aurobindo Pharma Limited | Pharmaceutical dosage forms comprising escitalopram in form of granules |
US7834201B2 (en) | 2005-06-22 | 2010-11-16 | H. Lundbeck A/S | Crystalline base of escitalopram and orodispersible tablets comprising escitalopram base |
TWI347942B (en) * | 2005-06-22 | 2011-09-01 | Lundbeck & Co As H | Crystalline base of escitalopram and orodispersible tablets comprising escitalopram base |
BRPI0606122A2 (pt) * | 2005-08-29 | 2009-06-02 | Teva Pharma | tadalafil particulado sólido que tem uma distribuição de tamanho de partìcula bimodal |
EA200801081A1 (ru) | 2005-10-14 | 2008-10-30 | Х. Лундбекк А/С | Способы лечения расстройств центральной нервной системы комбинацией малых доз эсциталопрама и бупропиона |
US20070134322A1 (en) * | 2005-12-14 | 2007-06-14 | Forest Laboratories, Inc. | Modified and pulsatile release pharmaceutical formulations of escitalopram |
GB0601286D0 (en) | 2006-01-23 | 2006-03-01 | Sandoz Ag | Asymmetric synthesis |
WO2008059514A2 (en) * | 2006-07-31 | 2008-05-22 | Cadila Healthcare Limited | Process for preparing escitalopram |
WO2008046617A1 (en) * | 2006-10-20 | 2008-04-24 | Ratiopharm Gmbh | Escitalopram and solid pharmaceutical composition comprising the same |
US20090048336A1 (en) * | 2007-08-17 | 2009-02-19 | Naveen Kumar Kolla | Escitalopram oxalate powders |
EP2291177A2 (en) * | 2008-05-05 | 2011-03-09 | Farmaprojects, S.A. | Stable pharmaceutical compositions and their processes for preparation suitable for industrial scale |
EP2116231A1 (en) | 2008-05-07 | 2009-11-11 | Hexal Ag | Granulate comprising escitalopram oxalate |
GR20080100696A (el) | 2008-10-23 | 2010-05-13 | Genepharm �.�. | Φαρμακοτεχνικη μορφη με βελτιωμενη γευση του φαρμακευτικα αποδεκτου αλατος εσιταλοπραμης |
ITMI20120448A1 (it) * | 2012-01-30 | 2013-07-31 | Carthesia Sas | Composizione liofilizzata di escitalopram ossalato per somministrazione sublinguale |
ITMI20120106A1 (it) * | 2012-01-30 | 2013-07-31 | Carthesia S A S | Pastiglie liofilizzate di escitalopram ossalato per somministrazione sublinguale |
CN106397249A (zh) * | 2015-08-03 | 2017-02-15 | 深圳信立泰药业股份有限公司 | 一种高稳定性lcz696结晶粉末及其制备方法 |
JP2018016569A (ja) * | 2016-07-26 | 2018-02-01 | 株式会社トクヤマ | (1s)−1−[3−(ジメチルアミノ)プロピル]−1−(4−フルオロフェニル)−1,3−ジヒドロイソベンゾフラン−5−カルボニトリル蓚酸塩の製造方法 |
WO2018190294A1 (ja) * | 2017-04-10 | 2018-10-18 | 東和薬品株式会社 | エスシタロプラム医薬組成物 |
CN107441052A (zh) * | 2017-06-21 | 2017-12-08 | 山东京卫制药有限公司 | 一种含有草酸艾司西酞普兰的片剂及其制备方法 |
KR102089737B1 (ko) * | 2017-11-01 | 2020-03-16 | 한국화학연구원 | 에씨탈로프람을 함유한 미립구형 서방출 주사제 및 그의 제조방법 |
JP7453859B2 (ja) | 2020-06-22 | 2024-03-21 | 東和薬品株式会社 | エスシタロプラム錠剤 |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1143703A (ja) * | 1965-03-18 | |||
GB1358915A (en) | 1971-09-13 | 1974-07-03 | Merck & Co Inc | Directly compressed tablet and composition therefor |
GB1526331A (en) * | 1976-01-14 | 1978-09-27 | Kefalas As | Phthalanes |
GB8419963D0 (en) | 1984-08-06 | 1984-09-12 | Lundbeck & Co As H | Intermediate compound and method |
EP0223403B1 (en) * | 1985-10-25 | 1993-08-04 | Beecham Group Plc | Piperidine derivative, its preparation, and its use as medicament |
GB8814057D0 (en) * | 1988-06-14 | 1988-07-20 | Lundbeck & Co As H | New enantiomers & their isolation |
US5296507A (en) * | 1990-09-06 | 1994-03-22 | H.Lundbeck A/S | Treatment of cerbrovascular disorders |
GB9325644D0 (en) | 1993-12-15 | 1994-02-16 | Smithkline Beecham Plc | Novel formulation |
US5683720A (en) * | 1994-10-28 | 1997-11-04 | Fuisz Technologies Ltd. | Liquiflash particles and method of making same |
EP0714663A3 (en) | 1994-11-28 | 1997-01-15 | Lilly Co Eli | Potentiation of drug responses by serotonin 1A receptor antagonists |
AU5966196A (en) | 1995-06-08 | 1997-01-09 | Eli Lilly And Company | Methods of treating cold and allergic rhinitis |
DE1015416T1 (de) | 1997-07-08 | 2000-10-05 | H. Lundbeck A/S, Kobenhavn-Valby | Verfahren zur herstellung von citalopram |
GB9714841D0 (en) | 1997-07-14 | 1997-09-17 | Smithkline Beecham Plc | Treatment method |
US5980941A (en) * | 1997-08-20 | 1999-11-09 | Fuisz Technologies Ltd. | Self-binding shearform compositions |
US5840334A (en) * | 1997-08-20 | 1998-11-24 | Fuisz Technologies Ltd. | Self-binding shearform compositions |
US5869098A (en) * | 1997-08-20 | 1999-02-09 | Fuisz Technologies Ltd. | Fast-dissolving comestible units formed under high-speed/high-pressure conditions |
UA62985C2 (en) | 1997-11-10 | 2004-01-15 | Lunnbeck As H | A method for the preparation of citalopram |
WO1998019512A2 (en) | 1997-11-11 | 1998-05-14 | H. Lundbeck A/S | Method for the preparation of citalopram |
NZ510858A (en) | 1998-10-20 | 2003-11-28 | H | Method for the preparation of citalopram |
TWI230618B (en) * | 1998-12-15 | 2005-04-11 | Gilead Sciences Inc | Pharmaceutical compositions of 9-[2-[[bis[(pivaloyloxy)methyl]phosphono]methoxy]ethyl]adenine and tablets or capsules containing the same |
ATE237604T1 (de) | 1999-04-14 | 2003-05-15 | Lundbeck & Co As H | Verfahren zur herstellung von citalopram |
ITMI991579A1 (it) | 1999-06-25 | 2001-01-15 | Lundbeck & Co As H | Metodo per la preparazione di citalopram |
AR021155A1 (es) | 1999-07-08 | 2002-06-12 | Lundbeck & Co As H | Tratamiento de desordenes neuroticos |
JP2003510266A (ja) * | 1999-09-28 | 2003-03-18 | ハー・ルンドベック・アクチエゼルスカベット | 溶融顆粒化された調合物及びこの調合物から製造された、放出が調節された投薬形 |
GB2357762B (en) | 2000-03-13 | 2002-01-30 | Lundbeck & Co As H | Crystalline base of citalopram |
US6977306B2 (en) * | 2000-05-02 | 2005-12-20 | Sumitomo Chemical Company, Limited | Citalopram hydrobromide crystal and method for crystallization thereof |
US20030232881A1 (en) * | 2000-10-27 | 2003-12-18 | H. Lundbeck A/S | Crystals of pharmaceutically acceptable salts of citalopram, methods of crystallization, and pharmaceutical compositions comprising them |
ATE352546T1 (de) * | 2001-07-31 | 2007-02-15 | Lundbeck & Co As H | Kristalline zusammensetzung enthaltend escitalopram |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012211186A (ja) * | 2001-07-31 | 2012-11-01 | H Lundbeck As | エスシタロプラムを含む結晶性組成物 |
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