Pharmaceutical compositions for the coordinated delivery of NSAIDs
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) esomeprazole, wherein at least a portion of said esomeprazole is not surrounded by an enteric coating; and
(b) naproxen surrounded by a coating that inhibits its release from said unit 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 esomeprazole such that upon introduction of said unit dosage form into a medium, at least a portion of said esomeprazole is released regardless of the pH of the medium; and wherein said unit dosage form sequentially releases said esomeprazole followed by said naproxen.
2. The pharmaceutical composition of claim 1 , wherein naproxen is present in said unit dosage form in an amount of 200-600 mg.
3. The pharmaceutical composition of claim 1 , wherein esomeprazole is present in said unit dosage form in an amount of from 5 to 100 mg.
4. The pharmaceutical composition of claim 1 , wherein naproxen is present in said unit dosage form in an amount of between 200-600 mg and esomeprazole in an amount of from 5 to 100 mg per unit dosage form.
5. The pharmaceutical composition of claim 1 , wherein said unit dosage form is a multilayer tablet comprising a core layer and one or more layers outside of said core layer.
6. The pharmaceutical composition of claim 5 , wherein said core layer comprises naproxen.
7. The pharmaceutical composition of claim 5 , wherein said one or more layers outside of said core layer do not contain naproxen.
8. The pharmaceutical composition of claim 1 , further comprising at least one carrier.
9. The pharmaceutical composition of claim 1 , further comprising at least one auxiliary agent chosen from the group consisting of lubricants, preservatives, disintegrants, stabilizers, wetting agents, emulsifiers, salts, buffers, coloring agents, flavoring agents, and aromatic substances.