Oral amphetamine composition

Abstract

In various embodiments, the present invention is directed to oral pharmaceutical compositions. For example, in some embodiments, the present invention is directed to taste-masked compositions. In some embodiments, the taste masked compositions comprise a highly water soluble drug such as amphetamine, e.g., in the form of a salt such as amphetamine sulfate. In various embodiments, the present invention is directed to taste-masked, orally disintegrating compositions.

1 . An orally disintegrating pharmaceutical composition comprising:
 (a) taste-masked drug containing particles comprising racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in a dose equivalent to 30 mg of racemic amphetamine sulfate and at least one excipient;   (b) a disintegrant;   (c) a sugar alcohol or saccharide, or mixture thereof;   wherein the taste-masked drug containing particles comprise:
 (i) a first taste-masking membrane comprising at least one pharmaceutically acceptable water insoluble polymer and having a membrane thickness of from about 5% to about 50% by wt of the taste-masked drug containing particle, and 
 (ii) a second taste-masking membrane comprising a pharmaceutically acceptable water insoluble polymer and a pharmaceutically acceptable gastrosoluble polymer at a ratio in the range of from about 95/5 to about 50/50; 
   wherein the first taste-masking membrane does not include a pharmaceutically acceptable gastrosoluble polymer; and   wherein said composition has an average patient perceptible intensity of bitterness of less than 1 minute when the orally disintegrating composition having a dose equivalent to 30 mg of racemic amphetamine sulfate is evaluated by a sensory panel using the flavor profile method;   wherein after administration of the dose equivalent to 30 mg of racemic amphetamine sulfate, the orally disintegrating pharmaceutical composition provides one or more of the following:   an AUC inf  ranging from about 80% to about 125% of about 400-600 hr*ng/mL,   a C max  ranging from about 80% to about 125% of about 25-35 ng/mL, or   a T max  ranging from about 80% to about 125% of about 2-4 hrs.   
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The orally disintegrating pharmaceutical composition of  claim 1 , wherein after administration of the dose equivalent to 30 mg of racemic amphetamine sulfate, the orally disintegrating pharmaceutical composition provides two or more of the following:
 an AUC inf  ranging from about 80% to about 125% of about 400-600 hr*ng/mL;   a C max  ranging from about 80% to about 125% of about 25-35 ng/mL; or   a T max  ranging from about 80% to about 125% of about 2-4 hrs.   
     
     
         5 . The orally disintegrating pharmaceutical composition of  claim 1 , wherein after administration of the dose equivalent to 30 mg of racemic amphetamine sulfate, the orally disintegrating pharmaceutical composition provides the following:
 an AUC inf  ranging from about 80% to about 125% of about 400-600 hr*ng/mL;   a C max  ranging from about 80% to about 125% of about 25-35 ng/mL; or   a T max  ranging from about 80% to about 125% of about 2-4 hrs.   
     
     
         6 . (canceled) 
     
     
         7 . The orally disintegrating pharmaceutical composition of  claim 1 , wherein the second taste-masking membrane is disposed over the first taste-masking membrane. 
     
     
         8 . The orally disintegrating pharmaceutical composition of  claim 1 , wherein the water insoluble polymer in the first taste-masking membrane is selected from the group consisting of ethylcellulose, cellulose acetate, cellulose acetate butyrate, polyvinyl acetate, and methacrylate copolymers. 
     
     
         9 . The orally disintegrating pharmaceutical composition of  claim 1 , wherein the water insoluble polymer in the second taste-masking membrane is selected from the group consisting of ethylcellulose, cellulose acetate, cellulose acetate butyrate, polyvinyl acetate, and methacrylate copolymers; and the gastrosoluble polymer in the second taste-masking membrane is aminoalkyl methacrylate copolymer. 
     
     
         10 . The orally disintegrating pharmaceutical composition of  claim 7 , wherein the water insoluble polymer in the second taste-masking membrane is ethylcellulose, and the gastrosoluble polymer in the second taste-masking membrane is aminoalkyl methacrylate copolymer. 
     
     
         11 . The orally disintegrating pharmaceutical composition of  claim 7 , wherein the water insoluble polymer in the first taste-masking membrane comprises is ethylcellulose, the water insoluble polymer in the second taste-masking membrane is ethylcellulose, and the gastrosoluble polymer in the second taste-masking membrane is aminoalkyl methacrylate copolymer. 
     
     
         12 . The orally disintegrating pharmaceutical composition of  claim 1 , wherein the taste-masking drug containing particles comprise an amphetamine sulfate-mannitol granulate. 
     
     
         13 . The orally disintegrating pharmaceutical composition of  claim 1 , wherein the taste-masking drug containing particles comprise an amphetamine sulfate layered bead. 
     
     
         14 . The orally disintegrating pharmaceutical composition of  claim 11 , wherein the taste-masking drug containing particles comprise an amphetamine sulfate-mannitol granulate. 
     
     
         15 . A method of treating a condition selected from the group consisting of narcolepsy, attention deficit disorder with hyperactivity, and exogenous obesity, comprising administering to a patient in need thereof the orally disintegrating pharmaceutical composition of  claim 1 . 
     
     
         16 . The method of  claim 1 , wherein the condition is attention deficit disorder with hyperactivity. 
     
     
         17 . A method of preparing the orally disintegrating pharmaceutical composition of  claim 1 , comprising:
 (a) preparing a drug-containing particle;   (b) disposing a first taste-masking membrane on said drug-containing particle, wherein said first taste-masking membrane comprises a water-insoluble polymer applied by solvent coacervation and does not include a pharmaceutically acceptable gastrosoluble polymer;   (c) disposing a second taste-masking membrane on said coacervated particle of step (b), wherein said second taste-masking membrane comprises a water-insoluble polymer and a gastrosoluble polymer; and   
       compressing the taste-masked drug containing particles of step (c) with optional excipients to form an orally disintegrating tablet. 
     
     
         18 . The method of  claim 17 , further comprising:
 (d) granulating one or more sugar alcohols and/or saccharides, each having an average particle diameter of not more than about 30 μm, with a disintegrant and drying the granulate to produce rapidly-dispersing microgranules with an average particle size of not more than about 400 μm;   (e) blending the taste-masked drug containing particles of step (c) with one or more flavoring agents, a sweetener, microcrystalline cellulose, additional disintegrant, and the rapidly-dispersing microgranules of step (d); and   (f) compressing the blend of step (e) into tablets.   
     
     
         19 . The method of  claim 17 , wherein the ratio of the water-insoluble polymer to the gastrosoluble polymer of the second taste-masking membrane ranges from about 95/5 to about 50/50. 
     
     
         20 . The method of  claim 19 , wherein the second taste-masking membrane is about 5% to about 50% of the weight of the coated particle. 
     
     
         21 . The method of  claim 20 , wherein the second taste-masking coating comprises ethyl cellulose and an aminoalkyl methacrylate copolymer.