Once-a-day oxycodone formulations

Abstract

The invention is directed to sustained release formulations containing oxycodone or a pharmaceutically acceptable salt thereof which provide a mean C 24 /C max oxycodone ratio of 0.6 to 1.0 or 0.7 to 1 after oral administration at steady state to patients and methods thereof.

1 - 22 . (canceled) 
     
     
         23 . A sustained release oral dosage form comprising:
 (a) a bilayer core comprising:
 (i) a drug layer comprising an analgesically effective amount of oxycodone or a pharmaceutically acceptable salt thereof; and 
 (ii) a displacement layer comprising an osmopolymer; and 
   (b) a semipermeable wall surrounding the bilayer core having a passageway disposed therein for the release of said oxycodone or pharmaceutically acceptable salt thereof;   said dosage form providing an analgesic effect for at least about 24 hours after steady-state oral administration to human patients; and   said dosage form providing a mean C 24 /C max  oxycodone ratio of 0.6 to 1.0 after oral administration at steady state to said patients.   
     
     
         24 . The dosage form of  claim 23 , which provides a mean T max  of oxycodone in about 2 to about 17 hours after administration at steady state to said patients. 
     
     
         25 . The dosage form of  claim 23 , which provides a mean T max  of oxycodone in about 8 to about 16 hours after administration at steady state to said patients. 
     
     
         26 . The dosage form of  claim 23 , which provides a mean W 50  of the oxycodone of between 4 and 24 hours after administration at steady state to said patients. 
     
     
         27 . The dosage form of  claim 23 , which provides a W 50  of the oxycodone of at least 12 hours after administration at steady state to said patients. 
     
     
         28 . The dosage form of  claim 23 , wherein said displacement layer further comprises an osmagent. 
     
     
         29 . The dosage form of  claim 28 , wherein said osmagent is selected from the group consisting of osmotic salts and osmotic carbohydrates. 
     
     
         30 . The dosage form of  claim 23 , wherein said pharmaceutically acceptable salt of oxycodone is oxycodone hydrochloride. 
     
     
         31 . The dosage form of  claim 23 , wherein said oxycodone or pharmaceutically acceptable salt thereof is in an amount of from about 5 to about 640 mg. 
     
     
         32 . The dosage form of  claim 23 , which provides a mean T max  of oxycodone which occurs at about 12 to about 16 hours after administration at steady state to said patients. 
     
     
         33 . The dosage form of  claim 23 , which provides a mean C 24 /C max  ratio of 0.7 to 0.99 after administration at steady state to said patients. 
     
     
         34 . The dosage form of  claim 23 , which provides a mean C 24 /C max  ratio of 0.8 to 0.95 after administration at steady state to said patients. 
     
     
         35 . The dosage form of  claim 23 , which provides an in-vitro release rate, of oxycodone or a pharmaceutically acceptable salt thereof, when measured by the USP Basket Method at 100 rpm in 900 ml aqueous buffer at a pH of between 1.6 and 7.2 at 37° C. of from 0% to about 40% at 1 hour, from about 8% to about 70% at 4 hours, from about 20% to about 80% at 8 hours, from about 30% to about 95% at 12 hours, from about 35% to about 95% at 18 hrs, and greater than about 50% at 24 hours. 
     
     
         36 . A method of treating pain in patients comprising: 
       orally administering to human patients a sustained release oral dosage form comprising
 (a) a bilayer core comprising:
 (i) a drug layer comprising an analgesically effective amount of oxycodone or a pharmaceutically acceptable salt thereof; and 
 (ii) a displacement layer comprising an osmopolymer; and 
 
 (b) a semipermeable wall surrounding the bilayer core having a passageway disposed therein for the release of said oxycodone or pharmaceutically acceptable salt thereof; 
 
       to provide an analgesic effect at least about 24 hours after oral administration at steady state to human patients; and to provide a mean C 24 /C max  oxycodone ratio of 0.6 to 1.0 after oral administration at steady state to said patients. 
     
     
         37 . The method of  claim 36 , which provides a mean T max  of oxycodone at about 2 to about 17 hours after administration at steady state to said patients. 
     
     
         38 . The method of  claim 36 , which provides a mean T max  of oxycodone at about 8 to about 16 hours after administration at steady state to said patients. 
     
     
         39 . The method of  claim 36 , which provides a W 50  of the oxycodone of between 4 and 24 hours after administration at steady state to said patients. 
     
     
         40 . The method of  claim 39 , which provides a W 50  of the oxycodone of at least 12 hours after administration at steady state to said patients. 
     
     
         41 . The method of  claim 36 , which provides a mean C 24 /C max  ratio of 0.7 to 0.99 after administration at steady state to said patients. 
     
     
         42 . The method of  claim 36 , which provides a mean C 24 /C max  ratio of 0.8 to 0.95 after administration at steady state to said patients. 
     
     
         43 . The method of  claim 36 , wherein said dosage form provides an in-vitro release rate of oxycodone or a pharmaceutically acceptable salt thereof, when measured by the USP Basket Method at 100 rpm in 900 ml aqueous buffer at a pH of between 1.6 and 7.2 at 37° C. of from 0% to about 40% at 1 hour, from about 8% to about 70% at 4 hours, from about 20% to about 80% at 8 hours, from about 30% to about 95% at 12 hours, from about 35% to about 95% at 18 hrs, and greater than about 50% at 24 hours. 
     
     
         44 - 71 . (canceled) 
     
     
         72 . The dosage form of  claim 23 , which is overcoated with an additional amount of oxycodone or a pharmaceutically acceptable salt thereof in an immediate release form. 
     
     
         73 . An osmotic dosage form comprising
 a homogeneous core comprising oxycodone or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable polymer; and   a semipermeable membrane having a passageway, the semipermeable membrane surrounding the homogeneous core;   wherein the dosage form provides an analgesic effect for at least about 24 hours and a mean C 24 /C max  oxycodone ratio of 0.7 to 1 after steady-state oral administration to human patients.   
     
     
         74 . The dosage form of  claim 73 , which is overcoated with additional oxycodone and pharmaceutically acceptable salt thereof in an immediate release form. 
     
     
         75 . The dosage form of  claim 73 , wherein the pharmaceutically acceptable polymer is polyethylene oxide. 
     
     
         76 . The dosage form of  claim 73 , further comprising a disintegrant. 
     
     
         77 . The dosage form of  claim 73 , further comprising an absorption enhancer. 
     
     
         78 . The dosage form of  claim 73 , wherein the semipermeable membrane comprises a poly(cellulose) with a number-average molecular weight of 20,000 to 7,500,000. 
     
     
         79 . The dosage form of  claim 78 , wherein the poly(cellulose) is selected from the group consisting of a cellulose ester polymer, a cellulose ether polymer and cellulose ester-ether polymer. 
     
     
         80 . An osmotic dosage form comprising:
 1 to 640 mg of oxycodone or a pharmaceutically acceptable salt thereof,   25 to 500 mg of poly(alkylene oxide having a 150,000 to 500,000 average molecular weight,   1 to 50 mg of polyvinylpyrrolidone) having a 40,000 average molecular weight, and   0 to about 7.5 mg of a lubricant,   wherein the dosage form provides an analgesic effect for at least about 24 hours and a mean C 24 /C max  oxycodone ratio of 0.7 to 1 after steady-state oral administration to human patients.