DK3173075T3 - Farmaceutisk kombinationspræparat af ace-inhibitor og loopdiuretikum - Google Patents
Farmaceutisk kombinationspræparat af ace-inhibitor og loopdiuretikum Download PDFInfo
- Publication number
- DK3173075T3 DK3173075T3 DK15003387.6T DK15003387T DK3173075T3 DK 3173075 T3 DK3173075 T3 DK 3173075T3 DK 15003387 T DK15003387 T DK 15003387T DK 3173075 T3 DK3173075 T3 DK 3173075T3
- Authority
- DK
- Denmark
- Prior art keywords
- torasemide
- lisinopril
- pharmaceutical combination
- composition according
- combination composition
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 18
- 239000005541 ACE inhibitor Substances 0.000 title claims description 7
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 title claims description 7
- 239000002171 loop diuretic Substances 0.000 title claims description 7
- NGBFQHCMQULJNZ-UHFFFAOYSA-N Torsemide Chemical compound CC(C)NC(=O)NS(=O)(=O)C1=CN=CC=C1NC1=CC=CC(C)=C1 NGBFQHCMQULJNZ-UHFFFAOYSA-N 0.000 claims description 65
- 229960005461 torasemide Drugs 0.000 claims description 65
- 229960002394 lisinopril Drugs 0.000 claims description 55
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 claims description 55
- 108010007859 Lisinopril Proteins 0.000 claims description 50
- 239000000203 mixture Substances 0.000 claims description 42
- 239000002245 particle Substances 0.000 claims description 16
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 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 7
- 229930195725 Mannitol Natural products 0.000 claims description 7
- 239000000594 mannitol Substances 0.000 claims description 7
- 235000010355 mannitol Nutrition 0.000 claims description 7
- 238000012986 modification Methods 0.000 claims description 7
- 230000004048 modification Effects 0.000 claims description 7
- 238000009826 distribution Methods 0.000 claims description 6
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 4
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims 2
- 238000003825 pressing Methods 0.000 claims 1
- 238000004090 dissolution Methods 0.000 description 14
- 239000013543 active substance Substances 0.000 description 8
- 239000008363 phosphate buffer Substances 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- 229920000881 Modified starch Polymers 0.000 description 4
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 4
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 235000019759 Maize starch Nutrition 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 235000019700 dicalcium phosphate Nutrition 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229960003883 furosemide Drugs 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 239000013066 combination product Substances 0.000 description 2
- 229940127555 combination product Drugs 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000007907 direct compression Methods 0.000 description 2
- 230000001882 diuretic effect Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000003921 particle size analysis Methods 0.000 description 2
- 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 description 1
- 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
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 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 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010033109 Ototoxicity Diseases 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 231100001124 band 1 compound Toxicity 0.000 description 1
- 231100001126 band 3 compound Toxicity 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 229960001021 lactose monohydrate Drugs 0.000 description 1
- 238000007561 laser diffraction method Methods 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 231100000262 ototoxicity Toxicity 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- FMLHTZVGNSACKP-UHFFFAOYSA-N pyridin-2-ylsulfonylurea Chemical compound NC(=O)NS(=O)(=O)C1=CC=CC=N1 FMLHTZVGNSACKP-UHFFFAOYSA-N 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 238000001507 sample dispersion Methods 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000002700 urine Anatomy 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
- A61K9/20—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
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
-
- 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
- A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
-
- 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
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Claims (15)
- FARMACEUTISK KOMBINATIONSPRÆPARAT AF ACE-INHIBITOR OG LOOP- DIURETIKUM1. Farmaceutisk kombinationspræparat af ACE-inhibitor og loop- diuretikum, kendetegnet ved, at det hårform afen tablet, der indeholder lisinopril og torasemid-modifikation I i farmaceutisk effektiv mængde, mikrokrystallinsk cellulose, stivelse, mannitol og glittemiddel, hvorved mindst 85 % lisinopril og mindst 85 % torasemid opløses fra tabletten i 15 minutter i buffer ved pH 4,5 under anvendelse af et skovlblanderapparat ved 75 o/m og 37,0 ± 0,5 °C.
- 2. Farmaceutisk kombinationspræparat ifølge krav 1, kendetegnet ved, at lisinopril forekommer i form af lisinoprildihydrat.
- 3. Farmaceutisk kombinationspræparat ifølge krav 1, kendetegnet ved, at tabletten fremstilles under anvendelse af en fremgangsmåde med direkte presning.
- 4. Farmaceutisk kombinationspræparat ifølge krav 1, kendetegnet ved, at mikrokrystallinsk cellulose forekommer i en mængde fra 20 % til 40 % af tablettens samlede vægt.
- 5. Farmaceutisk kombinationspræparat ifølge krav 1, kendetegnet ved, at stivelse forekommer i en mængde fra 10 % til 50 % af tablettens samlede vægt.
- 6. Farmaceutisk kombinationspræparat ifølge krav 1, kendetegnet ved, at mannitol forekommer i en mængde fra 10 % til 30 % af tablettens samlede vægt.
- 7. Farmaceutisk kombinationspræparat ifølge krav 1, kendetegnet ved, at sammensætningen omfatter 10 mg lisinopril og 10 mg torasemid.
- 8. Farmaceutisk kombinationspræparat ifølge krav 1, kendetegnet ved, at sammensætningen omfatter 20 mg lisinopril og 10 mg torasemid.
- 9. Farmaceutisk kombinationspræparat ifølge krav 1, kendetegnet ved, at sammensætningen omfatter 10 mg lisinopril og 5 mg torasemid.
- 10. Farmaceutisk kombinationspræparat ifølge krav 1, kendetegnet ved, at sammensætningen omfatter 20 mg lisinopril og 5 mg torasemid.
- 11. Farmaceutisk kombinationspræparat ifølge krav 1, kendetegnet ved, at det omfatter magnesiumstearat som glittemiddel.
- 12. Farmaceutisk kombinationspræparat ifølge krav 1, kendetegnet ved, at mindst 85 % lisinopril og mindst 85 % torasemid opløses fra tabletten i 15 minutter i buffer ved pH 6,8 under anvendelse af et skovlblanderapparat ved 75 o/m.
- 13. Farmaceutisk kombinationspræparat ifølge krav 1, kendetegnet ved, at 50 volumen-% torasemidpartikler har en diameter fra 20 pm til 80 pm, og 90 volumen-% torasemidpartikler har en diameter på under 100 pm.
- 14. Farmaceutisk kombinationspræparat ifølge krav 1, kendetegnet ved, at partikelstørrelsesfordelingen for torasemid er angivet ved d(0,5) fra 50 pm til 80 pm og d(0,9) under 100 pm.
- 15. Farmaceutisk kombinationspræparat ifølge krav 1, der omfatter fra 1 til 3 vægt-% torasemid og fra 2 til 5 vægt-% lisinopril.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15003387.6A EP3173075B1 (en) | 2015-11-27 | 2015-11-27 | Pharmaceutical combination preparation of ace inhibitor and loop diuretic |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK3173075T3 true DK3173075T3 (da) | 2019-01-21 |
Family
ID=54754405
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK15003387.6T DK3173075T3 (da) | 2015-11-27 | 2015-11-27 | Farmaceutisk kombinationspræparat af ace-inhibitor og loopdiuretikum |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP3173075B1 (da) |
| DK (1) | DK3173075T3 (da) |
| ES (1) | ES2703376T3 (da) |
| LT (1) | LT3173075T (da) |
| PL (1) | PL3173075T3 (da) |
| SI (1) | SI3173075T1 (da) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN119746022A (zh) * | 2024-12-27 | 2025-04-04 | 江苏天士力帝益药业有限公司 | 一种赖诺普利氢氯噻嗪药物组合物及其制备方法和应用 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3529529A1 (de) * | 1985-08-17 | 1987-02-19 | Boehringer Mannheim Gmbh | Verfahren zur herstellung einer stabilen modifikation von torasemid |
| DE3532036A1 (de) | 1985-09-09 | 1987-03-26 | Hoechst Ag | Pharmazeutische zubereitung zur behandlung des bluthochdrucks |
| CA2424644A1 (en) | 2003-04-07 | 2004-10-07 | David John Mckenzie | Preparation of torasemide |
-
2015
- 2015-11-27 DK DK15003387.6T patent/DK3173075T3/da active
- 2015-11-27 PL PL15003387T patent/PL3173075T3/pl unknown
- 2015-11-27 ES ES15003387T patent/ES2703376T3/es active Active
- 2015-11-27 EP EP15003387.6A patent/EP3173075B1/en active Active
- 2015-11-27 LT LTEP15003387.6T patent/LT3173075T/lt unknown
- 2015-11-27 SI SI201530541T patent/SI3173075T1/sl unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES2703376T3 (es) | 2019-03-08 |
| SI3173075T1 (sl) | 2019-02-28 |
| LT3173075T (lt) | 2019-01-10 |
| PL3173075T3 (pl) | 2019-04-30 |
| EP3173075B1 (en) | 2018-09-26 |
| EP3173075A1 (en) | 2017-05-31 |
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