Pharmaceutical Compositions

• US 20080058353A1
• Filed: 08/20/2007
• Published: 03/06/2008
• Est. Priority Date: 08/21/2006
• Status: Active Grant

• Current Assignee: Astrazeneca AB (Astrazeneca PLC)
• Original Assignee: Astrazeneca AB (Astrazeneca PLC)
• Inventors: Banks, Simon
• Granted Patent: US 8,425,934 B2
• Time in Patent Office: Days
• US Class Current: 514/261.1
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to pharmaceutical compositions and, more particularly, to a pharmaceutical composition containing the compound {1S-[1α, 2α, 3β (1S*,2R*),5β]}-3-(7-{[2-(3,4-difluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol.

Claims

1. A pharmaceutical composition comprising:

{1S-[1α

, 2α

, 3β

(1S*,2R*),5β

]}-3-(7-{[2-(3,4difluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol;

one or more fillers selected from mannitol, sorbitol, dibasic calcium phosphate dihydrate, dibasic calcium phosphate anhydrate, and tribasic calcium phosphate, or any mixture thereof,

one or more binders selected from hydroxypropyl cellulose, alginic acid, carboxymethylcellulose sodium, copovidone, and methylcellulose, or any mixture thereof;

one or more disintegrants selected from sodium starch glycolate, croscarmellose sodium, and crospovidone, or any mixture thereof, and

one or more lubricants.

2. A pharmaceutical composition according to claim 1 wherein the filler is a mixture of mannitol and dibasic calcium phosphate dihydrate.

3. A pharmaceutical composition according to claim 2 wherein the binder is hydroxypropyl cellulose.

4. A pharmaceutical composition according to claim 2 wherein the disintegrant is sodium starch glycolate.

5. A pharmaceutical composition according to claim 2 wherein the lubricant is magnesium stearate or sodium stearyl fumarate.

6. A pharmaceutical composition according to claim 2 wherein {1S-[1α

, 2α

, 3β

(1S*,2R*),5β

]}-3-(7-{[2-(3,4-difluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol is present in an amount of 20 to 45% by weight.

7. A pharmaceutical composition according to claim 2 wherein the filler is present in an amount of 20 to 70% by weight.

8. A pharmaceutical composition according to claim 2 wherein the binder is present in an amount of 3 to 6% by weight.

9. A pharmaceutical composition according to claim 2 wherein the disintegrant is present in an amount of 2 to 6% by weight.

10. A pharmaceutical composition according to claim 2 wherein the lubricant is present in an amount of 0.5 to 1% by weight.

11. A pharmaceutical composition according to claim 2 wherein {1S-[1α

, 2α

, 3β

(1S*,2R*),5β

]}-3-(7-{[2-(3,4-difluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol is substantially present in the form of Polymorph II.

12. A pharmaceutical composition according to claim 2 wherein {1S-[1α

, 2α

, 3β

(1S*,2R*),5β

]}-3-(7-{[2-(3,4-difluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol is substantially present in the form of Polymorph III.

13. A pharmaceutical composition according to claim 1 wherein:

the filler is a mixture of mannitol and dibasic calcium phosphate dehydrate;

the binder is hydroxypropyl cellulose;

the disintegrant is sodium starch glycolate; and

the lubricant is magnesium stearate or sodium stearyl fumarate.

14. A pharmaceutical composition according to claim 1 comprising:

{1S-[1α

, 2α

, 3β

(1S*,2R*),5β

]}-3-(7-{[2-(3,4-difluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol in an amount of 20 to 45% by weight;

mannitol in an amount of 20 to 45% by weight;

dibasic calcium phosphate dihydrate in an amount of 10 to 30% by weight;

hydroxypropylcellulose in an amount of 3 to 6% by weight;

sodium starch glycolate in an amount of 2 to 6% by weight; and

one or more lubricants in an amount of 0.5 to 3% by weight.

15. A pharmaceutical composition according to claim 1 which has been prepared by a wet granulation process.

16. A pharmaceutical composition according to claim 1 which has been prepared by a high shear wet granulation process.