Controlled dose drug delivery system

Abstract

A multiple pulsed dose drug delivery system for pharmaceutically active amphetamine salts, comprising a pharmaceutically active amphetamine salt covered with an immediate-release coating and a pharmaceutically active amphetamine salt covered with an enteric coating wherein the immediate release coating and the enteric coating provide for multiple pulsed dose delivery of the pharmaceutically active amphetamine salt. The product can be composed of either one or a number of beads in a dosage form, including either capsule, tablet, or sachet method for administering the beads.

1 - 58 . (canceled) 
     
     
         59 . A sustained release pharmaceutical composition comprising:
 (a) at least one amphetamine salt,   (b) a sustained release coating, and   (c) a delayed release coating,   wherein the sustained release coating is external to the delayed release coating and the at least one amphetamine salt is released about 4 to about 6 hours after oral administration of the composition to a patient.   
     
     
         60 . The pharmaceutical composition of  claim 59 , wherein about 50% of the at least one amphetamine salt is released after about six hours dissolution at a pH of about 7.5. 
     
     
         61 . The pharmaceutical composition of  claim 59 , comprising:
 (a) at least one amphetamine salt layered onto a core,   (b) a delayed release coating layered onto the at least one amphetamine salt layer;   (c) a sustained release coating layered onto the delayed release coating, and   (d) a protective coating layered onto the sustained release coating.   
     
     
         62 . The pharmaceutical composition of  claim 59 , wherein the at least one amphetamine salt comprises dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate, amphetamine sulfate, and mixtures thereof. 
     
     
         63 . The pharmaceutical composition of  claim 59 , wherein the delayed release coating is selected from the group consisting of: cellulose acetate phthalate; cellulose acetate trimellitate; hydroxypropyl methylcellulose phthalate; polyvinyl acetate phthalate; carboxymethylethylcellulose; co-polymerized methacrylic acid/methacrylic acid methyl esters, co-polymerized methacrylic acid/methyl methacrylate, and co-polymerized methylacrylate/methyl methacrylate/methacrylic acid. 
     
     
         64 . The pharmaceutical composition of  claim 63 , wherein the delayed release coating is a co-polymer of methylacrylate/methyl methacrylate/methacrylic acid. 
     
     
         65 . The pharmaceutical composition of  claim 59 , wherein the sustained release coating is selected from the group consisting of: polyvinyl acetate, cellulose acetate, cellulose acetate butyrate, cellulose acetate propionate, ethyl cellulose, fatty acids and esters thereof, alkyl alcohols, waxes, zein (prolamine from corn), co-polymerized ethyl acrylate/methyl methacrylate, co-polymerized ethylacrylate/methyl methacrylate/methacrylic acid with quaternary ammonium groups, ethyl acrylate/methyl methacrylate/methacrylic acid ester with quaternary ammonium groups, polyvinyl acetate, and cellulose acetate latex. 
     
     
         66 . The pharmaceutical composition of  claim 65 , wherein the sustained release coating is ethyl cellulose. 
     
     
         67 . The pharmaceutical composition of  claim 59 , comprising 12.5 mg of the at least one amphetamine salt. 
     
     
         68 . The pharmaceutical composition of  claim 67 , wherein the composition has a d-amphetamine AUC (O-inf) of about 367 ng·hr/mL. 
     
     
         69 . The pharmaceutical composition of  claim 67 , wherein the composition has an 1-amphetamine AUC (O-inf) of about 125 ng·hr/mL. 
     
     
         70 . The pharmaceutical composition of  claim 59 , wherein the composition comprises 18.75 mg, 25 mg, 31.25 mg, 37.5 mg, or 50 mg of at least one amphetamine salt and has a d-amphetamine AUC (0-inf) that is linearly proportional to the AUC (O-inf) for the 12.5 mg at least one amphetamine salt composition of claim  10 . 
     
     
         71 . The pharmaceutical composition of  claim 59 , wherein the composition comprises 18.75 mg, 25 mg, 31.25 mg, 37.5 mg, or 50 mg of at least one amphetamine salt and has a l-amphetamine AUC (0-inf) that is linearly proportional to the AUC (O-inf) for the 12.5 mg at least one amphetamine salt composition of claim  11 . 
     
     
         72 . The pharmaceutical composition of  claim 59 , comprising 12.5 mg of the at least one amphetamine salt; wherein the composition has a d-amphetamine Cmax of about 18.67 ng/mL. 
     
     
         73 . The pharmaceutical composition of  claim 59 , comprising 12.5 mg of the at least one amphetamine salt; wherein the composition has a 1-amphetamine Cmax of about 5.64 ng/mL. 
     
     
         74 . The pharmaceutical composition of  claim 59 , wherein the composition comprises 18.75 mg, 25 mg, 37.5 mg, or 50 mg of at least one amphetamine salt and has a d-amphetamine Cmax that is linearly proportional to the Cmax for the 12.5 mg at least one amphetamine salt composition of claim  14 . 
     
     
         75 . The pharmaceutical composition of  claim 59 , wherein the composition comprises 18.75 mg, 25 mg, 37.5 mg, or 50 mg of at least one amphetamine salt and has a l-amphetamine Cmax that is linearly proportional to the Cmax for the 12.5 mg at least one amphetamine salt composition of claim  15 . 
     
     
         76 . The pharmaceutical composition of  claim 59 , comprising 12.5 mg of the at least one amphetamine salt; wherein the composition has a d-amphetamine Tmax of about 8.83 hours. 
     
     
         77 . The pharmaceutical composition of  claim 59 , comprising 12.5 mg of the at least one amphetamine salt; wherein the composition has a 1-amphetamine Tmax of about 9.33 hours. 
     
     
         78 . The pharmaceutical composition of  claim 59 , wherein the composition comprises 18.75 mg, 25 mg, 37.5 mg, or 50 mg of at least one amphetamine salt and has a Tmax that is linearly proportional to the Tmax for the 12.5 mg at least one amphetamine salt composition of claim  9 . 
     
     
         79 . A method of treating ADHD comprising administering the pharmaceutical composition of  claim 59  in combination with an immediate release mixed amphetamine salt composition and/or an extended release mixed amphetamine salt composition to a patient in need of such treatment. 
     
     
         80 . The method of  claim 79 , wherein the pharmaceutical composition of claim  1  and the immediate release mixed amphetamine salt composition and/or the extended release mixed amphetamine salt composition are administered simultaneously. 
     
     
         81 . The method of  claim 79 , wherein the sustained release pharmaceutical composition comprises about 10% to about 150% of the amphetamine dosage of the immediate release mixed amphetamine salt composition and/or an extended release mixed amphetamine salt composition. 
     
     
         82 . The method of  claim 79 , wherein the immediate release mixed amphetamine salt composition and the extended release mixed amphetamine salt composition comprise one dosage unit. 
     
     
         83 . The method of  claim 80 , wherein the pharmaceutical composition of claim  1 , the immediate release mixed amphetamine salt composition and the extended release mixed amphetamine salt composition comprise one dosage unit.