DK2782557T3 - Farmaceutiske formuleringer - Google Patents
Farmaceutiske formuleringer Download PDFInfo
- Publication number
- DK2782557T3 DK2782557T3 DK12809882.9T DK12809882T DK2782557T3 DK 2782557 T3 DK2782557 T3 DK 2782557T3 DK 12809882 T DK12809882 T DK 12809882T DK 2782557 T3 DK2782557 T3 DK 2782557T3
- Authority
- DK
- Denmark
- Prior art keywords
- solid oral
- pharmaceutical formulation
- oral pharmaceutical
- group
- formulation
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title description 3
- 239000000203 mixture Substances 0.000 claims description 41
- 239000007787 solid Substances 0.000 claims description 31
- 238000009472 formulation Methods 0.000 claims description 28
- 239000008203 oral pharmaceutical composition Substances 0.000 claims description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 239000007962 solid dispersion Substances 0.000 claims description 18
- 239000011230 binding agent Substances 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 13
- 239000008384 inner phase Substances 0.000 claims description 13
- 239000002535 acidifier Substances 0.000 claims description 12
- 239000004094 surface-active agent Substances 0.000 claims description 12
- 239000000945 filler Substances 0.000 claims description 11
- 239000000314 lubricant Substances 0.000 claims description 11
- 239000012071 phase Substances 0.000 claims description 11
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 229940126062 Compound A Drugs 0.000 claims description 9
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 9
- 239000007884 disintegrant Substances 0.000 claims description 9
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- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 6
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
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- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
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- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 4
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- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 4
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- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
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- 229920001213 Polysorbate 20 Polymers 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
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- 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 description 2
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- 235000011037 adipic acid Nutrition 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
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- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 2
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- 229920003109 sodium starch glycolate Polymers 0.000 claims description 2
- 229940079832 sodium starch glycolate Drugs 0.000 claims description 2
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
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- 239000008385 outer phase Substances 0.000 claims 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 1
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- KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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- 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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- 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
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- 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
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- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
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- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
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Claims (21)
1. Fast oral farmaceutisk formulering, som omfatter: en indre fase, der er en fast dispersion, som omfatter amorft (S)-methyl-(1-((4-(3-(5-chlor-2-fluor-3-(methylsulfonamido)phenyl)-l-isopropyl-lH-pyrazol-4-yl)pyrimidin-2-yl)amino)propan-2-yl)carbamat (FORBINDELSE A) , et hydrofilt bindemiddel, et overfladeaktivt middel og en ydre fase, som omfatter et forsuringsmiddel, et fyldstof og et smøremiddel.
2. Fast oral farmaceutisk formulering ifølge krav 1, hvor den indre fase omfatter fra 5 til 40 vægt-% amorft (S)-methyl-(1- ( (4- (3- (5-chlor-2-fluor-3-(methylsulfonamido)phenyl)-1-isopropyl-lH-pyrazol-4-yl)pyrimidin-2-yl)amino)propan-2- yl) carbamat (Forbindelse A), fra 50 til 80 vægt-% af det hydrofile bindemiddel og fra 5 til 20 vægt-% af det overfladeaktive middel.
3. Fast oral farmaceutisk formulering ifølge krav 1, hvor det hydrofile bindemiddel er valgt fra gruppen bestående af copovidon, hydroxypropylmethylcellulose, polyvinylpyrrolidon, hydroxypropylcellulose, og methacrylatcopolymer, polyethylenoxid, hydroxypropylmethylcellulose (HPMC)- acetatsuccinat og hydroxypropylmethylcellulose (HPMC)-phthalat.
4. Fast oral farmaceutisk formulering ifølge krav 3, hvor det hydrofile bindemiddel er copovidon.
5. Fast oral farmaceutisk formulering ifølge krav 1, hvor det overfladeaktive middel er valgt fra gruppen bestående af poloxamerer, natriumlaurylsulfat, sorbitol, polysorbat 20, polysorbat 80, E-vitamin-TPGS og polyethylenglycol.
6. Fast oral farmaceutisk formulering ifølge krav 5, hvor poloxameren er poloxamer 188. Ί. Fast oral farmaceutisk formulering ifølge krav 1, hvor den ydre fase omfatter fra 10 til 40 vægt-% af forsuringsmidlet, fra 20 til 40 vægt-% af fyldstoffet og fra 1 til 5 vægt-% af smøremidlet, hvor den ydre fase endvidere omfatter fra 1 til 15 vægt-% af et desintegrationsmiddel og fra 1 til 5 vægt-% af et strømningsforbedrende middel.
8. Fast oral farmaceutisk formulering ifølge krav 1, hvor forsuringsmidlet er valgt fra gruppen bestående af citronsyre, ravsyre, maleinsyre, vinsyre, æblesyre og adipinsyre.
9. Fast oral farmaceutisk formulering ifølge krav 1, hvor fyldstoffet er valgt fra gruppen bestående af lactose, maltodextrin, mannitol, mikrokrystallinsk cellulose, prægelatineret stivelse og saccharoseestere.
10. Fast oral farmaceutisk formulering ifølge krav 7, hvor desintegrationsmidlet er valgt fra gruppen bestående af crospovidon, croscarmellosenatrium, natriumstivelsesglycolat, mikrokrystallinsk cellulose og prægelatineret stivelse.
11. Fast oral farmaceutisk formulering ifølge krav 7, hvor det strømningsforbedrende middel er valgt fra gruppen bestående af kolloid silica, talkum, magnesiumstearat og mannitol.
12. Fast oral farmaceutisk formulering ifølge krav 1, hvor smøremidlet er valgt fra gruppen bestående af magnesiumstearat, calciumstearat, glycerylmonostearat, hydrogeneret ricinusolie, natriumlaurylsulfat, natriumstearylfumarat, stearinsyre, zinkstearat, talkum, mikrokrystallinsk cellulose og saccharoseestere.
13. Fast oral farmaceutisk formulering ifølge krav 1, som omfatter en blanding af den indre fase og den ydre fase i et forhold på fra 80:20 til 40:60.
14. Fast oral farmaceutisk formulering ifølge krav 13, som omfatter en blanding af den indre fase og den ydre fase i et forhold på fra 75:25 til 50:50.
15. Fast oral formulering ifølge krav 1, som er formuleret som en kapsel eller tablet.
16. Fast oral farmaceutisk formulering ifølge krav 15, som omfatter 10 mg, 20 mg, 25 mg, 50 mg, 100 mg, 200 mg, 400 mg eller 500 mg amorft (S)-methyl-(1-((4-(3-(5-chlor-2-fluor-3-(methylsulfonamido)phenyl)-l-isopropyl-lH-pyrazol-4- yl)pyrimidin-2-yl)amino)propan-2-yl)carbamat (Forbindelse A).
17. Fast oral farmaceutisk formulering ifølge krav 1, hvor formuleringen er en kapsel valgt fra gruppen bestående af: A)
og B)
18. Fast oral formulering ifølge krav 1, hvor formuleringen er en kapsel valgt fra gruppen bestående af:
19. Fast oral farmaceutisk formulering ifølge et hvilket som helst af kravene 1-18 til anvendelse ved behandling af en
proliferativ sygdom.
20. Fast oral farmaceutisk formulering ifølge et hvilket som helst af kravene 1-18 til anvendelse ved behandling af en sygdom, som reagerer på hæmning af B-RAF.
21. Fast oral farmaceutisk formulering til anvendelse ifølge krav 20, hvor sygdommen er kendetegnet ved en mutation i B-RAF.
22. Fast oral farmaceutisk formulering til anvendelse ifølge krav 21, hvor sygdommen er melanom eller kolorektal cancer.
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| US10449195B2 (en) | 2016-03-29 | 2019-10-22 | Shenzhen Pharmacin Co., Ltd. | Pharmaceutical formulation of palbociclib and a preparation method thereof |
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2012
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