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 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.