Controlled release hydrocodone formulations

Abstract

A solid oral controlled-release dosage form of hydrocodone is disclosed, the dosage form comprising an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof, and controlled release material.

1 - 38 . (canceled) 
     
     
         39 . A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising (i) hydrocodone or a pharmaceutically acceptable salt thereof, (ii) an anti-inflammatory agent or a pharmaceutically acceptable salt thereof and (iii) and a controlled release material comprising a material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, shellac, oils, and mixtures thereof,
 the dosage form providing a ratio of a plasma concentration of hydrocodone at the end of a dosing interval to a maximum plasma concentration of hydrocodone during the dosing interval of from 0.55 to 1 and effective pain relief over a period of time of about 12 hours or longer after administration to a human patient, wherein   the hydrocodone or pharmaceutically acceptable salt thereof and the anti-inflammatory agent or pharmaceutically acceptable salt thereof are the only active agents in the dosage form.   
     
     
         40 . The dosage form of  claim 39 , wherein the dosage form comprises a matrix comprising the hydrocodone or pharmaceutically acceptable salt thereof and the controlled-release material. 
     
     
         41 . The dosage form of  claim 39 , wherein said administration is first administration. 
     
     
         42 . The dosage form of  claim 41 , wherein the controlled release material comprises a cellulose ether. 
     
     
         43 . A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising (i) hydrocodone or a pharmaceutically acceptable salt thereof, (ii) an anti-inflammatory agent or a pharmaceutically acceptable salt thereof and (iii) and a controlled release material comprising a material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, shellac, oils, and mixtures thereof,
 the dosage form providing a W 50  of hydrocodone of between 4 and 22 hours and a plasma concentration of hydrocodone within a therapeutic range over a period of time of about 12 hours or longer after administration to a human patient, wherein   the hydrocodone or pharmaceutically acceptable salt thereof and the anti-inflammatory agent or pharmaceutically acceptable salt thereof are the only active agents in the dosage form.   
     
     
         44 . The dosage form of  claim 43 , wherein the dosage form provides the plasma concentration of hydrocodone within the therapeutic range over a period of time of about 12 hours after administration to the human patient. 
     
     
         45 . The dosage form of  claim 44 , wherein said administration is first administration. 
     
     
         46 . The dosage form of  claim 43 , wherein said administration is first administration. 
     
     
         47 . The dosage form of  claim 43 , wherein the controlled release material comprises a cellulose ether. 
     
     
         48 . The dosage form of  claim 45 , wherein the dosage form provides a C 24 /C max  hydrocodone ratio of from 0.55 to 1 after said administration and a therapeutic effect for about 24 hours. 
     
     
         49 . The dosage form of  claim 45 , wherein the dosage form provides a T max  of hydrocodone of from about 4 to about 14 hours and a plasma concentration of hydrocodone within a therapeutic range over a period of time of about 12 hours or longer after administration to a human patient. 
     
     
         50 . The dosage form of  claim 49 , wherein the dosage form provides the plasma concentration of hydrocodone within the therapeutic range over a period of time of about 12 hours after administration to the human patient. 
     
     
         51 . The dosage form of  claim 50 , wherein said administration is first administration. 
     
     
         52 . The dosage form of  claim 49 , wherein said administration is first administration. 
     
     
         53 . The dosage form of  claim 39 , wherein the dosage form provides a mean C 24 /C max  hydrocodone ratio of from 0.55 to 1 and a therapeutic effect for about 24 hours after administration to a patient population and the dosing interval is 24 hours. 
     
     
         54 . The dosage form of  claim 39 , wherein the dosage form provides a C 24 /C max  hydrocodone ratio of from 0.55 to 1 and a therapeutic effect for about 24 hours after administration to the human patient and the dosing interval is 24 hours. 
     
     
         55 . The dosage form of  claim 39 , wherein the anti-inflammatory agent is selected from the group consisting of ibuprofen, diclofenac, naproxen, benoxaprofen, flurbiprofen, fenoprofen, flubufen, ketoprofen, indoprofen, piroprofen, carprofen, oxaprozin, pramoprofen, muroprofen, trioxaprofen, suprofen, aminoprofen, tiaprofenic acid, fluprofen, bucloxic acid, indomethacin, sulindac, tolmetin, zomepirac, tiopinac, zidometacin, acemetacin, fentiazac, clidanac, oxpinac, mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid tolfenamic acid, diflurisal, flufenisal, piroxicam, sudoxicam, isoxicam, celecoxib, meloxicam, nabumetone. 
     
     
         56 . The dosage form of  claim 39 , wherein the anti-inflammatory agent is a cyclo-oxygenase inhibitor. 
     
     
         57 . The dosage form of  claim 56 , wherein the controlled release material comprises a cellulose ether. 
     
     
         58 . The dosage form of  claim 39 , wherein the controlled release material is included in an effective amount such that the dosage form provides an in-vitro release of hydrocodone when measured by the USP Basket method at 100 rpm in 700 ml aqueous buffer at a pH of 1.2 at 37° C. of from 10% to about 45% by weight hydrocodone released at 1 hour. 
     
     
         59 . A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising
 (i) hydrocodone or a pharmaceutically acceptable salt thereof, (ii) an anti-inflammatory agent or a pharmaceutically acceptable salt thereof and (iii) a pharmaceutically acceptable polymer, the pharmaceutically acceptable polymer comprising between 1% and 80% of the dosage form by weight,   the dosage form providing an in-vitro release rate of hydrocodone, 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 35% at 1 hour, from about 10% to about 70% at 4 hours, from about 20% to about 75% at 8 hours, from about 30% to about 80% at 12 hours, from about 40% to about 90% at 18 hours, and greater than about 60% at 24 hours,   wherein the dosage form provides a plasma concentration profile of hydrocodone with a ratio of the plasma concentration of hydrocodone at 24 hours after administration to the highest concentration of hydrocodone during the 24 hours of from 0.55 to 1.0,   maintains the plasma concentrations of hydrocodone within the therapeutic range over 12 hours or longer after administration to a human and is administrable on a once a day basis.   
     
     
         60 . The dosage form of  claim 59 , wherein the dosage form maintains therapeutically effective plasma concentrations of hydrocodone for about 24 hours after administration. 
     
     
         61 . The formulation of  claim 39 , wherein the formulation provides a plasma concentration profile of hydrocodone with a ratio of the plasma concentration of hydrocodone at 24 hours after administration to the highest concentration of hydrocodone during the 24 hours of 0.55 to 0.85.