Pharmaceutical compositions for the coordinated delivery of NSAIDs
View Patent ↗The present invention is directed to drug dosage forms that release an agent that raises the pH of a patient's gastrointestinal tract, followed by a non-steroidal anti-inflammatory drug. The dosage form is designed so that the NSAID is not released until the intragastric pH has been raised to a safe level. The invention also encompasses methods of treating patients by administering this coordinated release, gastroprotective, antiarthritic/analgesic combination unit dosage form to achieve pain and symptom relief with a reduced risk of developing gastrointestinal damage such as ulcers, erosions and hemorrhages.
1. A pharmaceutical composition in unit dosage form comprising therapeutically effective amounts of:
(a) a proton pump inhibitor selected from the group consisting of omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole, wherein at least a portion of said proton pump inhibitor is not surrounded by an enteric coating; and
(b) aspirin, wherein said aspirin is surrounded by a coating that inhibits its release from said dosage form unless said dosage form is in a medium with a pH of 3.5 or higher;
wherein said unit dosage form provides for release of said proton pump inhibitor and said aspirin such that:
i) upon introduction of said unit dosage form into a medium, at least a portion of said proton pump inhibitor is released regardless of the pH of the medium; and
ii) said aspirin is released when the pH of said medium is 3.5 or higher.
2. The pharmaceutical composition of claim 1 , wherein said aspirin is present in said unit dosage form in an amount of 20-200 mg.
3. The pharmaceutical composition of claim 1 , wherein said proton pump inhibitor is omeprazole in an amount of from 5 to 50 mg per unit dosage form.
4. A method of treating a patient to reduce inflammation, comprising administering to said patient the pharmaceutical composition of claim 1 .
5. The method of claim 4 , wherein said pharmaceutical composition is administered to reduce the risk of stroke or heart attack.
6. The pharmaceutical composition of claim 1 , wherein said proton pump inhibitor is omeprazole.
7. The pharmaceutical composition of claim 6 , wherein said omeprazole is in an amount of 10 or 20 mg per unit dosage form.
8. The pharmaceutical composition of claim 1 , wherein said aspirin is present in said unit dosage form in an amount of 40-100 mg.
9. The pharmaceutical composition of claim 1 , wherein said aspirin is present in said unit dosage form in an amount of 250-1000 mg.
10. The pharmaceutical composition of claim 1 , wherein said aspirin is present in said unit dosage form in an amount of 250-1000 mg and said proton pump inhibitor is omeprazole in an amount of 10 or 20 mg per unit dosage form.
11. The pharmaceutical composition of claim 1 , wherein said aspirin is present in said unit dosage form in an amount of 20-200 mg and said proton pump inhibitor is omeprazole in an amount of 5-50 mg per unit dosage form.
12. The pharmaceutical composition of claim 1 , wherein said aspirin is present in said unit dosage form in an amount of 20-200 mg and said proton pump inhibitor is omeprazole in an amount of 10 or 20 mg per unit dosage form.
13. The pharmaceutical composition of claim 6 , wherein said unit dosage form is a tablet comprising an inner core of said aspirin surrounded by a barrier coating that does not dissolve unless the pH of the surrounding medium is 3.5 or greater.
14. The pharmaceutical composition of claim 6 , wherein said unit dosage form is a tablet comprising an inner core of said aspirin surrounded by a barrier coating that does not dissolve unless the pH of the surrounding medium is 4 or greater.
15. The pharmaceutical composition of claim 6 , wherein said unit dosage form is a tablet comprising an inner core of said aspirin surrounded by a barrier coating that does not dissolve unless the pH of the surrounding medium is 5 or greater.
16. The pharmaceutical composition of claim 6 wherein said unit dosage form is a multilayer tablet comprising a single core and one or more layers outside of said single core, wherein:
i) said aspirin is present in said core and is surrounded by a coating that does not release said aspirin unless the pH of the surrounding medium is 3.5 or higher; and
ii) said omeprazole is in said one or more layers outside said core.
17. The pharmaceutical composition of claim 16 , wherein said one or more layers outside of said core do not contain aspirin and are not surrounded by an enteric coating.
18. The pharmaceutical composition of claim 6 , wherein said unit dosage form is a bilayer tablet having an outer layer of said omeprazole and an inner core of said aspirin and wherein said outer layer of said tablet is surrounded by a non-enteric film coating, wherein said tablet releases said omeprazole upon ingestion by a patient.
19. The pharmaceutical composition of claim 1 , wherein said unit dosage form is a capsule.
20. A method of treating a patient to reduce inflammation, comprising administering to said patient the pharmaceutical composition of claim 6 .
21. The method of claim 20 , wherein said pharmaceutical composition is administered to reduce the risk of stroke or heart attack.
22. A pharmaceutical composition in unit dosage form comprising therapeutically effective amounts of:
(a) omeprazole, wherein at least a portion of said omeprazole is not surrounded by an enteric coating; and
(b) aspirin, wherein said aspirin is surrounded by a coating that inhibits its release from said dosage form unless said dosage form is in a medium with a pH of 3.5 or higher;
wherein said unit dosage form provides for release of said omeprazole and said aspirin such that:
i) upon introduction of said unit dosage form into a medium, at least a portion of said omeprazole is released regardless of the pH of the medium;
ii) said aspirin is released when the pH of said medium is 3.5 or higher; and
iii) said aspirin is present in said unit dosage form in an amount of 40-100 mg and said omeprazole is present in said unit dosage form in an amount of 5-50 mg per unit dosage form.
23. A pharmaceutical composition in unit dosage form comprising therapeutically effective amounts of:
(a) omeprazole, wherein at least a portion of said omeprazole is not surrounded by an enteric coating; and
(b) aspirin, wherein said aspirin is surrounded by a coating that inhibits its release from said dosage form unless said dosage form is in a medium with a pH of 3.5 or higher;
wherein said unit dosage form provides for release of said omeprazole and said aspirin such that:
i) upon introduction of said unit dosage form into a medium, at least a portion of said omeprazole is released regardless of the pH of the medium;
ii) said aspirin is released when the pH of said medium is 3.5 or higher; and
iii) said aspirin is present in said unit dosage form in an amount of 250-1000 mg and said omeprazole is present in said unit dosage form in an amount of 5-50 mg per unit dosage form.