|Title:||Pharmaceutical compositions for the coordinated delivery of NSAIDs|
|Abstract:||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.|
|Inventor(s):||Plachetka; John R. (Chapel Hill, NC)|
|Assignee:||Pozen Inc. (Chapel Hill, NC)|
|Filing Date:||Apr 01, 2014|
|Claims:||1. A process for preparing a pharmaceutical composition in unit dosage form comprising therapeutically effective amounts of esomeprazole and naproxen, said process comprising the steps of: a) providing a first layer comprising said naproxen; and b) applying a second layer to said first layer, wherein said second layer comprises said esomeprazole; 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 release of at least a portion of said naproxen is inhibited unless the pH of said medium is 3.5 or higher. |
2. The process of claim 1, wherein said first layer further comprises one or more excipients chosen from pharmaceutically acceptable fillers, binding agents, disintegrants, and lubricants.
3. The process of claim 1, wherein said first layer comprises 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.
4. The process of claim 1, wherein said first layer comprises a core layer comprising said naproxen and an enteric film coat that surrounds the core layer.
5. The process of claim 4, wherein the enteric film coat comprises hydroxypropylmethylcellulose phthalate.
6. The process of claim 1, wherein said first layer comprises a core layer comprising said naproxen, a barrier layer that surrounds the core layer, and an enteric film coat that surrounds the barrier layer.
7. The process of claim 1, wherein said second layer further comprises one or more excipients chosen from plasticizers, anti-adhering agents, lubricating ingredients, opacifiers, and excipients that adjust the pH.
8. The process of claim 1, wherein the second layer is applied by pan coating.