Method for Delivering A Pharmaceutical Composition to Patient in Need Thereof

• US 20100062064A1
• Filed: 09/03/2009
• Published: 03/11/2010
• Est. Priority Date: 09/09/2008
• Status: Active Grant

• Current Assignee: Horizon Therapeutics USA, Inc. (Amgen Inc.), Nuvo Pharmaceuticals (Ireland) Designated Activity Company
• Original Assignee: Pozen Incorporated (Aralez Pharmaceuticals Inc.), Astrazeneca UK Limited (Astrazeneca PLC)
• Inventors: Orlemans, Everardus, Sostek, Mark, Ault, Brian, Plachetka, John R.
• Granted Patent: US 9,220,698 B2
• Time in Patent Office: Days
• US Class Current: 424/475
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The present disclosure is directed to a method for delivering a pharmaceutical composition to a patient in need thereof, comprising: administering to said patient a pharmaceutical composition in unit dose form comprising naproxen, or pharmaceutically acceptable salt thereof, and esomeprazole, or pharmaceutically acceptable salt thereof

Claims

1-18. -18. (canceled)

19. A method for delivering a pharmaceutical composition to a patient in need thereof, comprising:

administering to said patient a pharmaceutical composition in unit dose form comprising naproxen, or pharmaceutically acceptable salt thereof, and esomeprazole, or pharmaceutically acceptable salt thereof, wherein said esomeprazole, or pharmaceutically acceptable salt thereof, is released from said unit dose form at a pH of from about 0 or greater, wherein one unit dose form is administered as an AM dose and a second dose administered about 10 hours later as a PM dose to target;

i) a pharmacokinetic (pk) profile for naproxen where;

a) the AM dose has a mean C_max of about 81 μ

g/mL and a median time to maximum concentration (T_max) of from about 2.5 to about 4 hours, and

b) the PM dose has a mean C_max of about 76.2 μ

g/mL and a median T_max of from about 10 to about 14 hours; and

ii) a pharmacokinetic (pk) profile for esomeprazole where;

a) the AM dose has a mean area under the plasma concentration-time curve from time zero when the AM dose is administered to about 10 hours after the AM dose is administered (AUC_0-10,am) of about 850 hr/*μ

g/mL, and

b) the PM dose has a mean area under the plasma concentration-time curve from time zero when the PM dose is administered to about 14 hours after the PM dose is administered (AUC_0-14,pm) of about 650 hr*μ

g/mL.

20. The method according to claim 19, wherein:

a) the mean C_max for said AM dose of naproxen is about 86.2 μ

g/mL and said median T_max is about 3.0 hours; and

a) the mean C_max for said PM dose is about 76.8 μ

g/mL and said median T_max is about 10 hours.

21. The method according to claim 19, wherein:

a) the mean C_max for said AM dose of naproxen is about 80.9 μ

g/mL and said median T_max is about 3.0 hours; and

b) the mean C_max for said PM dose is about 76.2 μ

g/mL and said median T_max is about 10.4 hours.

22. The method according to claim 19, wherein

a) the mean area under the plasma concentration-time curve from time zero when the AM dose is administered to about 10 hours after the AM dose is administered (AUC_0-10,am) for said AM dose of esomeprazole is about 1216 hr*μ

g/mL, and

b) the mean area under the plasma concentration-time curve from time zero when the PM dose is administered to about 14 hours after the PM dose is administered (AUC_0-14,pm) for said PM dose of esomeprazole is about 919 hr*μ

g/mL.

23. The method according to claim 19, wherein

a) the mean area under the plasma concentration-time curve from time zero when the AM dose is administered to about 10 hours after the AM dose is administered (AUC_0-10,am) for said AM dose of esomeprazole is about 2779 hr*μ

g/mL, and

b) the mean area under the plasma concentration-time curve from time zero when the PM dose is administered to about 14 hours after the PM dose is administered (AUC_0-14,pm) for said PM dose of esomeprazole is about 2066 hr*μ

g/mL.

24. The method according to claim 19, wherein said pharmaceutical composition further targets a pharmacokinetic (pk) profile having a mean area under the plasma concentration-time curve from time zero when first dose is administered to about 24 hours after the first dose is administered (AUC_0-24) for esomeprazole is about 1500 hr*μ

g/mL.

25. The method according to claim 24, wherein the mean area under the plasma concentration-time curve from time zero when first dose is administered to about 24 hours after the first dose is administered (AUC_0-24) for esomeprazole is about 2000 hr*μ

g/mL.

26. The method according to claim 24, wherein the mean area under the plasma concentration-time curve from time zero when first dose is administered to about 24 hours after the first dose is administered (AUC_0-24) for esomeprazole is about 4911 hr*μ

g/mL.

27. The method according to claim 19, wherein the pharmaceutical composition further targets a mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period after reaching steady state of at least about 41%.

28. The method according to claim 27, wherein the mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period after reaching steady state is at least about 60%.

29. The method according to claim 27, wherein the mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period after reaching steady state is at least about 71%.

30. The method according to claim 27, wherein the mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period after reaching steady state is at least about 77%.

31. The method according to claim 19, wherein said pharmaceutical composition in unit dose form comprises about 500 mg of said naproxen and about 20mg of said esomeprazole.

33. The method according to claim 19, wherein said unit dose form is administered for a period of at least about 6 days.

34. The method according to claim 19, wherein said unit dose form is administered for a period of at least about 9 days.

38. The method according to claim 19, wherein said patient in need thereof is being treated for a disease or disorder selected from pain and inflammation.

39. The method according to claim 19, wherein said patient in need thereof is being treated for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, or a combination thereof.

40. The method according to claim 19, wherein said unit dose form is a multilayer tablet comprising at least one core and at least a first layer and a second layer, wherein:

i) said core comprises naproxen, or pharmaceutically acceptable salt thereof;

ii) said first layer is a coating that at least begins to release the naproxen, or pharmaceutically acceptable salt thereof, when the pH of the surrounding medium is about 3.5 or greater; and

iii) said second layer comprises esomeprazole, wherein said esomeprazole is released at a pH of from about 0 or greater.

42. The method according to claim 40, wherein said esomeprazole is released at a pH of from about 0 to about 2.

45. The method according to claim 40, wherein said multi-layer tablet is substantially free of sodium bicarbonate.

32. (canceled)

35-37. -37. (canceled)

41. (canceled)

43-44. -44. (canceled)

46-47. -47. (canceled)