Gastric retentive extended release pharmaceutical compositions

Abstract

The present disclosure provides extended release pharmaceutical compositions comprising an opioid and an additional active pharmaceutical ingredient, wherein the composition exhibits gastric retentive properties which are achieved by a combination of a physical property of the composition and release of the opioid, wherein upon administration to a subject, the composition has at least one pharmacokinetic parameter that differs by less than about 30% when the subject is in a fasted state as compared to a fed state.

What is claimed is: 
     
         1 . A method of treating acute pain in a human subject comprising:
 administering to the subject in need thereof a solid oral dosage form comprising:   (a) at least one immediate release portion comprising acetaminophen in an amount selected from the group consisting of about 125 mg to about 325 mg, and hydrocodone or a pharmaceutically acceptable salt thereof in an amount selected from the group consisting of about 1.5 mg to about 4.0 mg; and   (b) at least one extended release portion comprising acetaminophen in an amount selected from the group consisting of about 125 mg to about 325 mg, and hydrocodone or a pharmaceutically acceptable salt thereof in an amount selected from the group consisting of about 4.5 mg to about 6.5 mg wherein the total amount of acetaminophen in the solid oral dosage form is 325 mg and the total amount of hydrocodone or a pharmaceutically acceptable salt in the solid oral dosage form is about 7.5 mg; and   wherein upon administration of two solid oral dosage forms the subject attains therapeutic blood levels of both the hydrocodone and the acetaminophen within about one hour after administration of the solid oral dosage forms and maintains analgesia for about 12 hours after administration of the solid oral dosage forms.   
     
     
         2 . The method of  claim 1 , wherein upon administration to the subject, the solid oral dosage forms produce a plasma profile characterized by a biphasic absorption of the hydrocodone. 
     
     
         3 . The method of  claim 1 , wherein when orally administered to the subject, the solid oral dosage form produces a plasma profile characterized by a biphasic absorption of the acetaminophen. 
     
     
         4 . The method of  claim 3 , wherein the biphasic absorption of the acetaminophen results in a first peak in the plasma concentration for the acetaminophen between about 0.5 hour and about 2 hours, which contributes to an early onset of analgesia, and a second peak in the plasma concentration for the acetaminophen between about 3 hours and about 7 hours which contributes to the duration or maintenance of analgesia. 
     
     
         5 . The method on  claim 4 , wherein the slope of the plasma concentration-time profile for the acetaminophen between about 0 hour and about 2 hours is greater than the slope of a line drawn between about 2 hours and about 5 hours. 
     
     
         6 . The method of  claim 1 , wherein the solid oral dosage form is administered to the subject in need thereof twice a day. 
     
     
         7 . The method of  claim 1 , wherein the solid oral dosage form further comprises an extended release component. 
     
     
         8 . The method of  claim 7 , wherein the extended release component is an extended release polymer. 
     
     
         9 . The method of  claim 8 , wherein the extended release polymer is polyethylene oxide. 
     
     
         10 . A method of treating acute pain in a human subject over a 12-hour dosing cycle comprising:
 administering to the subject in need thereof a solid oral dosage form comprising:   (a) at least one immediate release portion comprising about 125 mg to about 325 mg of acetaminophen and about 1.5 mg to about 4.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof; and   (b) at least one extended release portion comprising about 125 mg to about 325 mg of acetaminophen and about 4.5 mg to about 6.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof;   wherein the total amount of acetaminophen in the solid oral dosage form is 325 mg and the total amount of hydrocodone or a pharmaceutically acceptable salt in the solid oral dosage form is about 7.5 mg;   wherein upon placement of the solid oral dosage form in an in vitro dissolution test comprising USP Paddle Method at a paddle speed of about 100 rpm in 900 ml of 0.1 N HCl using a USP type II apparatus at a constant temperature of 37° C., the drug release profile substantially corresponds to the following: after 15 minutes, about 20% to about 40%, by weight, of the total amount of hydrocodone or salt thereof in the solid oral dosage form is released and about 50% to about 55%, by weight, of the total amount of acetaminophen in the solid oral dosage form is released; after 1 hour, about 40% to about 50%, by weight, of the total amount of hydrocodone or salt thereof in the solid oral dosage form is released and about 50% to about 70%, by weight, of the total amount of acetaminophen in the solid oral dosage form is released; and after 12 hours, from about 95% to about 100%, by weight, of the total amount of the hydrocodone or salt is released and from about 90% to about 100%, by weight, of the total amount of the acetaminophen is released.   
     
     
         11 . The method of  claim 10 , wherein the solid oral dosage form may be administered to the subject without regard to food. 
     
     
         12 . The method according to  claim 10 , wherein more than about 90% of the acetaminophen in the immediate release portion is released within about 5 mins. 
     
     
         13 . The method according to  claim 10 , wherein more than about 90% of the acetaminophen in the immediate release portion is released within about 15 mins. 
     
     
         14 . The method according to  claim 10 , wherein more than about 90% of the hydrocodone or pharmaceutically acceptable salt thereof in the immediate release portion is released within about 5 mins. 
     
     
         15 . The method according to  claim 10 , wherein more than about 90% of the hydrocodone or pharmaceutically acceptable salt thereof in the immediate release portion is released within about 15 mins. 
     
     
         16 . A method of treating acute pain in a human subject over a 12-hour dosing cycle comprising: administering to the subject in need thereof a solid oral dosage form comprising:
 (a) at least one immediate release portion comprising about 125 mg to about 325 mg of acetaminophen, and about 1.5 mg to about 4.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof; and   (b) at least one extended release portion comprising about 125 mg to about 325 mg of acetaminophen, and about 4.5 mg to about 6.5 mg of hydrocodone or a pharmaceutically acceptable salt thereof;   wherein the total amount of acetaminophen in the solid oral dosage form is 325 mg and the total amount of hydrocodone or a pharmaceutically acceptable salt in the solid oral dosage form is about 7.5 mg; and   wherein upon administration of the solid oral dosage form the subject, the solid oral dosage form produces a mean AUC for hydrocodone from about 12.0 ng·hr/mL/mg to about 19.0 ng·hr/mL/mg and a mean AUC for acetaminophen from about 35.0 ng·hr/mL/mg to about 80.0 ng·hr/mL/mg.   
     
     
         17 . The method of  claim 16 , wherein upon administration of the solid oral dosage form the subject, the solid oral dosage form produces a C max  for hydrocodone from about 0.9 ng/mL/mg to about 2.0 ng/mL/mg and a C max  for acetaminophen from about 4.0 ng/mL/mg to about 11.0 ng/mL/mg. 
     
     
         18 . The method of  claim 16 , wherein upon administration of the solid oral dosage form the subject, the solid oral dosage form produces a T max  for hydrocodone from about 2 hours to about 8 hours, and a T max  for acetaminophen from about 0.5 hour to about 6 hours. 
     
     
         19 . The method of  claim 16 , wherein upon administration of the solid oral dosage form the subject, the solid oral dosage form produces a C max  for acetaminophen within about 0.75 hours to about 1.5 hours. 
     
     
         20 . The method of  claim 16 , wherein upon administration of the solid oral dosage form the subject, the solid oral dosage form produces a C max  for acetaminophen within about one hour.