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 treating osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis comprising orally administering to a patient in need thereof an AM unit dose form and, 10 hours (±20%) later, a PM unit dose form, wherein:
the AM and PM unit dose forms each comprises:
naproxen, or a pharmaceutically acceptable salt thereof, in an amount to provide 500 mg of naproxen, and
esomeprazole, or a pharmaceutically acceptable salt thereof, in an amount to provide 20 mg of esomeprazole;
said esomeprazole, or pharmaceutically acceptable salt thereof, is released from said AM and PM unit dose forms at a pH of 0 or greater,
the AM and PM unit dose forms target:
i) a pharmacokinetic (pk) profile for naproxen where:
a) for the AM dose of naproxen, the mean C max is 86.2 μg/mL (±20%) and the median T max is 3.0 hours (±20%); and
b) for the PM dose of naproxen, the mean C max is 76.8 μg/mL (±20%) and the median T max is 10 hours (±20%); and
ii) a pharmacokinetic (pk) profile for esomeprazole where:
a) for the AM dose of esomeprazole, the mean area under the plasma concentration-time curve from when the AM dose is administered to 10 hours (±20%) after the AM dose is administered (AUC 0-10,am ) is 1216 hr*μg/mL (±20%),
b) for the PM dose of esomeprazole, the mean area under the plasma concentration-time curve from when the PM dose is administered to 14 hours (±20%) after the PM dose is administered (AUC 0-14,pm ) is 919 hr*μg/mL (±20%), and
c) the total mean area under the plasma concentration-time curve for esomeprazole from when the AM dose is administered to 24 hours (±20%) after the AM dose is administered (AUC 0-24 ) is 2000 hr*μg/mL (±20%); and
the AM and PM unit dose forms further target a mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period after reaching steady state that is at least about 60%.
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 after reaching steady state is at least about 71%.
3. The method according to claim 1 , wherein said AM and PM unit dose forms are administered for a period of at least about 6 days.
4. The method according to claim 1 , wherein said AM and PM unit dose forms are administered for a period of at least about 9 days.
5. The method according to claim 1 , wherein said AM and PM unit dose forms are each 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 or a pharmaceutically acceptable salt thereof, wherein said esomeprazole or pharmaceutically acceptable salt thereof is released at a pH of from 0 or greater.
6. The method according to claim 5 , wherein said esomeprazole or pharmaceutically acceptable salt thereof is released at a pH of from 0 to about 2.
7. The method according to claim 5 , wherein said multi-layer tablet is substantially free of sodium bicarbonate.