Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic

Abstract

Compositions and methods for the treatment of pain in a mammal are described. More specifically, a dosage form designed for release of acetaminophen and an opioid is described, wherein the dosage form provides delivery of the drugs to the upper gastrointestinal tract (“GI”) of a mammal for an extended period of time.

1 . (canceled) 
     
     
         2 . A solid oral dosage form, comprising:
 an immediate release portion comprising a first dose of acetaminophen and a first dose of opioid;   an extended release portion comprising a second dose of acetaminophen and a second dose of opioid thereof in a hydrophilic polymer that swells upon imbibition of fluid to a size sufficient to promote gastric retention of the extended release portion in a gastrointestinal tract of a subject,   wherein said second doses of opioid and acetaminophen are released from the dosage form such that substantially all of each of the second doses is released within about ten hours, when measured in an in vitro disintegration test using a USP apparatus at 37° C. in 0.1N HCl;   wherein upon oral administration of the dosage form to a subject, the opioid does not significantly affect the erosion time of the dosage form.   
     
     
         3 . The dosage form of  claim 2 , wherein the first dose and the second dose of opioid comprise an opioid selected from the group consisting of oxycodone or hydrocodone, or pharmaceutically acceptable salts thereof. 
     
     
         4 . The dosage form of  claim 2 , wherein the sum of the doses of acetaminophen in the immediate release and extended release portions is about 325 mg. 
     
     
         5 . The dosage form of  claim 2 , wherein the opioid is oxycodone or a pharmaceutically acceptable salt thereof. 
     
     
         6 . The dosage form of  claim 3 , wherein the sum of the doses of oxycodone or a pharmaceutically acceptable salt thereof in the immediate release and extended release portions is about 7.5 mg. 
     
     
         7 . The dosage form of  claim 2 , wherein the opioid is hydrocodone or a pharmaceutically acceptable salt thereof. 
     
     
         8 . The dosage form of  claim 2 , wherein the hydrophilic polymer is present in an amount ranging from about 35 wt % to about 50 wt % of the extended release portion. 
     
     
         9 . The dosage form of  claim 2 , wherein the immediate release portion of the dosage form and the extended release portion of the dosage form comprise a bilayer tablet. 
     
     
         10 . A solid oral dosage form, comprising:
 an immediate release portion comprising a first dose of acetaminophen and a first dose of opioid selected from the group consisting of oxycodone or hydrocodone, or pharmaceutically acceptable salts thereof;   an extended release portion comprising a second dose of acetaminophen and a second dose of opioid selected from the group consisting of oxycodone or hydrocodone, or pharmaceutically acceptable salts thereof in a hydrophilic polymer that swells upon imbibition of fluid to a size sufficient to promote gastric retention of the extended release portion in a gastrointestinal tract of a subject;   wherein the acetaminophen and the opioid are released during a period of gastric retention of between about 4 hours to about 8 hours after oral administration;   wherein doses of acetaminophen are released from the dosage form such that about 40% to about 65% of the acetaminophen and about 20% to about 55% of the opioid are released from the dosage form within one hour, and substantially all of the acetaminophen and the opioid are released from the dosage form within about ten hours, when measured in an in vitro disintegration test using a USP apparatus at 37° C. in 0.1N HCl;   wherein the sum of the doses of acetaminophen in the immediate release and extended release portions is about 325 mg, and the sum of the doses of the opioid in the immediate release and extended portions is about 7.5 mg.   
     
     
         11 . The dosage form of  claim 10 , further comprising a chelating agent, wherein the chelating agent is present in the extended release portion at an amount ranging from about 0.01 wt % to about 0.1 wt %. 
     
     
         12 . The dosage form of  claim 10 , further comprising an antioxidant, wherein said antioxidant is present in the extended release portion at an amount ranging from about 0.05 wt % to about 0.35 wt %. 
     
     
         13 . The dosage form of  claim 12 , wherein the antioxidant is citric acid. 
     
     
         14 . The dosage form of  claim 10 , wherein the hydrophilic polymer is present in the extended release portion in an amount ranging from about 25 wt % to about 55 wt %. 
     
     
         15 . The dosage form of  claim 14 , wherein the hydrophilic polymer is selected from the group consisting of polyalkylene oxides, cellulosic polymers, poly(acrylamides), poly(olefinic alcohols), poly(N-vinyl-lactams), polyvinylamines, polyvinylacetates and polyimines. 
     
     
         16 . The dosage form of  claim 10 , wherein the polymer is present in the extended release portion in an amount ranging from about 30 wt % to about 50 wt %. 
     
     
         17 . The dosage form of  claim 10 , further comprising a disintegrant in the immediate release portion. 
     
     
         18 . The dosage form of  claim 10 , wherein upon oral administration of the dosage form to a subject the opioid does not significantly affect the erosion time of the dosage form.