Method for delivering a pharmaceutical composition to patient in need thereof
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.
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 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 to target:
a) a mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period of at least about 41%.
2. The method according to claim 1 , wherein the mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period is at least about 60%.
3. The method according to claim 1 , wherein the mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period is at least about 71%.
4. The method according to claim 1 , wherein the mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period is at least about 77%.
5. The method according to claim 1 , wherein said pharmaceutical composition in unit dose form comprises about 500 mg of said naproxen, or pharmaceutically acceptable salt thereof, and about 20 mg of said esomeprazole, or pharmaceutically acceptable salt thereof.
6. The method according to claim 1 , wherein said patient in need thereof is an at risk patient.
7. The method according to claim 6 , wherein said at risk patient is being treated for a disease or disorder selected from pain and inflammation.
8. The method according to claim 6 , wherein said at risk patient is being treated for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, or a combination thereof.
9. 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 μg/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 μg/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*ng/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*ng/mL.
10. The method according to claim 9 , 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 of at least about 41%.
11. The method according to claim 10 , wherein the mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period is at least about 60%.
12. The method according to claim 10 , wherein the mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period is at least about 71%.
13. The method according to claim 10 , wherein the mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period is at least about 77%.
14. The method according to claim 9 , wherein said pharmaceutical composition in unit dose form comprises about 500 mg of said naproxen and about 20 mg of said esomeprazole.
15. The method according to claim 9 , wherein said patient in need thereof is an at risk patient.
16. The method according to claim 15 , wherein said at risk patient is being treated for a disease or disorder selected from pain and inflammation.
17. The method according to claim 15 , wherein said at risk patient is being treated for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, or a combination thereof.
18. 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 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 is esomeprazole, wherein said esomeprazole is released at a pH of from about 0 or greater.
19. The method according to claim 18 , wherein at least a portion of said esomeprazole, or pharmaceutically acceptable salt thereof, is not coated with an enteric coating.
20. The method according to claim 18 , wherein said first layer is an enteric coating.