COMPOSITIONS AND METHODS FOR DELIVERY OF OMEPRAZOLE PLUS ACETYLSALICYLIC ACID

• US 20140370088A1
• Filed: 12/27/2012
• Published: 12/18/2014
• Est. Priority Date: 12/28/2011
• Status: Active Grant

• Current Assignee: Genus Lifesciences, Inc. (Vyteris, Inc.)
• Original Assignee: Pozen Incorporated (Aralez Pharmaceuticals Inc.)
• Inventors: Plachetka, John R.
• Granted Patent: US 9,539,214 B2
• Time in Patent Office: Days
• US Class Current: 424/474
• 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 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• 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 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 acetylsalicylic acid, or pharmaceutically acceptable salt thereof, and omeprazole, or pharmaceutically acceptable salt thereof.

Claims

1. 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 acetylsalicylic acid, or pharmaceutically acceptable salt thereof, and omeprazole, or pharmaceutically acceptable salt thereof, wherein said omeprazole, 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 to target:

i) a pharmacokinetic (pk) profile for acetylsalicylic acid where;

a) the dose has a acetylsalicylic acid mean C_max of about 2.0 to about 3.0 μ

g/mL and a median time to maximum concentration (T_max) of from about 3.0 to about 3.5 hours, and/or

b) the dose has a salicylic acid mean C_max of about 15 to about 16.5 μ

g/mL and a median time to maximum concentration (T_max) of from about 3.0 to about 3.5 hours,

ii) a pharmacokinetic (pk) profile for omeprazole where the dose has a mean area under the plasma concentration-time curve from time zero when the dose is administered to about 12 hours after the dose is administered (AUC_0-12) of about 0.8 to about 2.5 hr/*μ

g/mL.

2. The method according to claim 1, 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 50%.

3. The method according to claim 2, wherein the pk profile for acetylsalicylic acid has a mean acetylsalicylic acid C_max of at least 2.36 μ

g/ml and a mean salicylic acid C_max of at least 15.3 μ

g/ml.

4. The method according to claim 2, wherein the pk profile for acetylsalicylic acid has a mean acetylsalicylic acid C_max of about 2.91 μ

g/ml and a mean salicylic acid C_max of at least 16.2 μ

g/ml.

5. The method according to claim 4, wherein the % coefficient of variation for acetylsalicylic acid is about 54%, and the coefficient of variation for salicylic acid is about 29%.

6. The method according to claim 2, wherein the omeprazole mean area under the plasma concentration-time curve from time zero when the dose is administered to about 12 hours after the dose is administered (AUC_0-12) is about 2.174 hr/*μ

g/mL.

7. The method according to claim 6, wherein the % coefficient of variation for the omeprazole mean area under the plasma concentration-time curve from time zero when the dose is administered to about 12 hours after the dose is administered (AUC_0-12) is about 88%.

8. The method according to claim 2, wherein the omeprazole mean area under the plasma concentration-time curve from time zero when the dose is administered to about 24 hours after the dose is administered (AUC_0-24) of about 2.187 hr/*μ

g/mL.

9. The method according to claim 8, wherein the % coefficient of variation for the omeprazole mean area under the plasma concentration-time curve from time zero when the dose is administered to about 24 hours after the dose is administered (AUC_0-24) is about 88%.

10. The method according to claim 1, wherein said pharmaceutical composition in unit dose form comprises about 325 mg of said acetylsalicylic acid and about 40 mg of said omeprazole.

11. The method according to claim 1, wherein said unit dose form is administered for a period of at least about 7 days.

12. The method according to claim 1, wherein said unit dose form is administered for a period of at least about 14 days.

13. The method according to claim 1, 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 acetylsalicylic acid, or pharmaceutically acceptable salt thereof;

ii) said first layer is a coating that at least begins to dissolve when the pH of the surrounding medium is about 3.5 or greater; and

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

14. The method according to claim 13, wherein said omeprazole is released at a pH of from about 0 to about 2.

15. The method according to claim 1, wherein said patient in need thereof is being treated for a disease or disorder selected from pain and inflammation.

16. The method according to claim 1, wherein said patient in need thereof is being treated for cardiovascular disease, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, or a combination thereof.