Controlled release hydrocodone formulations

Abstract

A solid oral controlled-release oral dosage form of hydrocodone is disclosed. The dosage form comprising an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof, and a sufficient amount of a controlled release material to render the dosage form suitable for twice-a-day administration to a human patient, the dosage form providing a C 12 /C max ratio of 0.55 to 0.85, said dosage form providing a therapeutic effect for at least about 12 hours.

1 - 41 . (canceled) 
     
     
         42 . A solid oral dosage form of hydrocodone comprising:
 a tablet core and a controlled release coating over the tablet core,   wherein from about 0.5 mg to about 1250 mg hydrocodone or an equivalent amount of a pharmaceutically acceptable salt thereof is present in the dosage form,   the dosage form releases hydrocodone for about 12 hours or longer and   provides a plasma concentration profile of hydrocodone with a C 12 /C max  hydrocodone ratio of 0.55 to 0.85.   
     
     
         43 . The dosage form of  claim 42 , which releases hydrocodone for about 12 hours. 
     
     
         44 . The dosage form of  claim 42 , which releases hydrocodone for about 24 hours. 
     
     
         45 . The dosage form of  claim 42 , which provides a hydrocodone plasma concentration of at least about 8 ng/ml at about 2 hours after administration. 
     
     
         46 . The dosage form of  claim 45 , which comprises a pharmaceutically acceptable polymer. 
     
     
         47 . The dosage form of  claim 46 , wherein the pharmaceutically acceptable polymer comprises between 1% and 80% of the dosage form by weight. 
     
     
         48 . The dosage form of  claim 42 , which comprises a material having a melting point of from 30 to about 200° C. 
     
     
         49 . The dosage form of  claim 46 , wherein the pharmaceutically acceptable polymer is a hydroxyalkylcellulose. 
     
     
         50 . The dosage form of  claim 49 , wherein the hydroxyalkylcellulose is a hydroxypropyl cellulose or a hydroxypropylmethylcellulose. 
     
     
         51 . The dosage form of  claim 50 , wherein the hydroxyalkylcellulose is the hydroxypropylmethyl cellulose. 
     
     
         52 . The dosage form of  claim 48 , wherein the material is a polyalkylene glycol. 
     
     
         53 . The dosage form of  claim 42 , which provides a C max  that increases linearly from one dosage strength to another. 
     
     
         54 . The dosage form of  claim 44 , which provides a hydrocodone plasma concentration of at least about 8 ng/ml at about 8 hours after administration, and a hydrocodone plasma concentration of at least 5 ng/ml at 12 hours after administration. 
     
     
         55 . The dosage form of  claim 54 , which provides a plasma concentration profile of hydrocodone with a C 12 /C max  hydrocodone ratio of 0.55 to 0.65. 
     
     
         56 . The dosage form of  claim 55 , wherein the dosage form provides a plasma concentration profile of hydrocodone with a C 12 /C max  hydrocodone ratio of 0.65 to 0.85. 
     
     
         57 . The dosage form of  claim 55 , wherein said C 12 /C max  hydrocodone ratio is calculated from hydrocodone plasma concentrations from first administration of the dosage form to a population of fasted humans. 
     
     
         58 . The dosage form of  claim 56 , wherein said C 12 /C max  hydrocodone ratio is calculated from hydrocodone plasma concentrations from first administration of the dosage form to a population of fasted humans. 
     
     
         59 . The dosage form of  claim 55 , wherein a portion of the plasma concentration profile of hydrocodone is relatively flat. 
     
     
         60 . The dosage form of  claim 55 , wherein said C 12 /C max  hydrocodone ratio is calculated from hydrocodone plasma concentrations from first administration of the dosage form to a fed human. 
     
     
         61 . The dosage form of  claim 56 , wherein said C 12 /C max  hydrocodone ratio is calculated from hydrocodone plasma concentrations from first administration of the dosage form to a fed human. 
     
     
         62 . The dosage form of  claim 54 , wherein said C 12 /C max  hydrocodone ratio is calculated from hydrocodone plasma concentrations from first administration of the dosage form to a population of fed humans. 
     
     
         63 . The dosage form of  claim 54 , wherein said hydrocodone plasma concentrations are hydrocodone plasma concentrations from first administration of the dosage form to a fasted human. 
     
     
         64 . The dosage form of  claim 54 , wherein said hydrocodone plasma concentrations are hydrocodone plasma concentrations from first administration of the dosage form to a fed human. 
     
     
         65 . A solid oral dosage form of hydrocodone comprising:
 a tablet core and a controlled release coating over the tablet core,   wherein from about 0.5 mg to about 1250 mg hydrocodone or an equivalent amount of a pharmaceutically acceptable salt thereof is present in the dosage form,   the dosage form releases hydrocodone for about 8 to about 24 hours and   provides a hydrocodone plasma concentration of at least about 8 ng/ml at about 8 hours after administration and a hydrocodone plasma concentration of at least 5 ng/ml at 12 hours after administration.   
     
     
         66 . The dosage form of  claim 65 , wherein the tablet comprises a bitartrate salt of hydrocodone. 
     
     
         67 . The dosage form of  claim 65 , wherein the dosage form provides a hydrocodone plasma concentration of at least about 8 ng/ml at about 2 hours after administration. 
     
     
         68 . The dosage form of  claim 65 , wherein the dosage form provides a plasma concentration profile of hydrocodone with a C 12 /C max  hydrocodone ratio of 0.55 to 0.85. 
     
     
         69 . The dosage form of  claim 68 , wherein a portion of the plasma concentration profile of hydrocodone is relatively flat. 
     
     
         70 . The dosage form of  claim 68 , wherein said C 12 /C max  hydrocodone ratio is calculated from hydrocodone plasma concentrations from first administration of the dosage form to a fasted human. 
     
     
         71 . The dosage form of  claim 65 , wherein said hydrocodone plasma concentrations are hydrocodone plasma concentrations from first administration of the dosage form to a fed human. 
     
     
         72 . A solid oral dosage form of hydrocodone comprising:
 a tablet core and a controlled release coating over the tablet core,   wherein hydrocodone is included as a bitartrate salt,   the dosage form releases hydrocodone for about 12 hours or longer and, after first administration, provides a hydrocodone plasma concentration of at least 6 ng/ml at about 12 hours, a hydrocodone plasma concentration of at least about 8 ng/ml at about 8 hours, and a C 12 /C max  hydrocodone ratio of 0.55 to 0.85.