Sustained release delivery of amphetamine salts

Abstract

A pharmaceutical composition comprises a once-a-day sustained release formulation of at least one amphetamine salt which provides mean plasma concentration profile aspects in human ADHD patients which are substantially the same as that provided by ADDERALL XR® type pulsatile formulations.

1 . A pharmaceutical composition comprising a once-a-day sustained release formulation of at least one amphetamine salt which provides a mean plasma concentration profile in human ADHD patients which is substantially the same as that provided by a formulation thereof comprising an immediate release dose and a dose delayed therefrom by about 2 to about 6 hours.  
     
     
         2 . A pharmaceutical composition of  claim 1  wherein the immediate and delayed release doses are the same.  
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the at least one amphetamine or amphetamine salt is a mixture of two or more amphetamine salts.  
     
     
         4 . The pharmaceutical composition of  claim 2 , wherein at least one amphetamine or amphetamine salt is a mixture of dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate and amphetamine sulfate.  
     
     
         5 . A pharmaceutical composition of  claim 4 , wherein said profile is substantially the same as that of  FIG. 1 .  
     
     
         6 . A pharmaceutical composition comprising a once-a-day sustained release formulation of at least one amphetamine salt which provides a mean plasma concentration profile in human ADHD patients which is substantially the same as that of  FIG. 1 .  
     
     
         7 . The composition of  claim 6 , wherein at least one amphetamine or amphetamine salt is a mixture of dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate and amphetamine sulfate.  
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein the dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate and amphetamine sulfate salts are administered in equal amounts by weight.  
     
     
         9 . The pharmaceutical composition of  claim 6 , wherein the at least one amphetamine or amphetamine salt is provided in a core which is coated with a coating comprising a pharmaceutically acceptable water-insoluble film former or other polymer providing sustained release.  
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein the coating further comprises a dissolution regulating agent.  
     
     
         11 . A pharmaceutical composition of  claim 1  comprising a sustained-release formulation of said salt(s) and a dosage form for immediate release of at least one amphetamine salt.  
     
     
         12 . The pharmaceutical composition of  claim 6 , wherein the at least one amphetamine or amphetamine salt is provided in a sustained release matrix.  
     
     
         13 . A method for treating attention deficit hyperactivity disorder which comprises administering to a human patient in need thereof a pharmaceutical composition of  claim 1 .  
     
     
         14 . A method for treating attention deficit hyperactivity disorder which comprises administering to a human patient in need thereof a pharmaceutical composition of  claim 5 .  
     
     
         15 . A method for treating attention deficit hyperactivity disorder which comprises administering to a human patient in need thereof a pharmaceutical composition of  claim 6 .  
     
     
         16 . A pharmaceutical composition comprising a once-a-day sustained release formulation of at least one amphetamine salt which provides a mean plasma concentration profile in human ADHD patients which has substantially the same initial slope as that of  FIG. 1 .  
     
     
         17 . A pharmaceutical composition comprising a once-a-day sustained release formulation of amphetamine salts which provides a mean plasma concentration profile in human ADHD patients which has an initial slope of about 3.7 to about 11.4 ng/(mL hr) for dextroamphetamines and about 1.4 to about 3 ng/(mL hr) for levoamphetamines, all at a total amphetamine dose of 20 mg, or an initial slope directly proportional thereto for a total dose other than 20 mg.  
     
     
         18 . A pharmaceutical composition comprising a once-a-day sustained release formulation of at least one amphetamine salt which provides a mean plasma concentration profile in human ADHD patients which has an initial slope of about 4 to about 8 ng/(mL hr) for dextroamphetamines and about 1.5 to about 2.2 ng/(mL hr) for levoamphetamines.  
     
     
         19 . A method for treating attention deficit hyperactivity disorder which comprises administering to a human patient in need thereof a pharmaceutical composition of  claim 16 .  
     
     
         20 . A method for treating attention deficit hyperactivity disorder which comprises administering to a human patient in need thereof a pharmaceutical composition of  claim 17 .  
     
     
         21 . A pharmaceutical composition comprising a once-a-day sustained release formulation of at least one amphetamine salt which provides a mean plasma concentration profile in human ADHD patients which has an AUC of 556.6 mg hr/mL±20% and a C max  of 28.0 ng/mL±20% for d-amphetamine and an AUC of 205.1 ng hr/mL±20% and a C max  of 8.7 ng/mL±20% for l-amphetamine.  
     
     
         22 . A method for treating attention deficit hyperactivity disorder which comprises administering to a human patient in need thereof a once-a-day sustained release formulation which provides a mean plasma concentration profile in human ADHD patients which has an AUC of 556.6 mg hr/mL±20% and a C max  of 28.0 ng/mL±20% for d-amphetamine and an AUC of 205.1 ng hr/mL±20% and a C max  of 8.7 ng/mL±20% for l-amphetamine.