Polar Hydrophilic Prodrugs of Amphetamine and Other Stimulants and Processes for Making and Using the Same

Abstract

Disclosed are amphetamine prodrug compositions comprising at least one non-standard amino acid conjugate of amphetamine, a salt thereof, or a combination thereof, and methods of using the same.

1 . A method for treating a patient having a disorder or condition requiring the stimulation of the central nervous system of the patient, comprising orally administering to the patient a pharmaceutically effective amount of at least one conjugate, a salt of the conjugate thereof, or a combination thereof, wherein the conjugate comprises amphetamine and homoarginine. 
     
     
         2 . The method of  claim 1 , wherein the at least one conjugate is l-homoarginine-d-amphetamine. 
     
     
         3 . The method of  claim 1 , wherein said step of orally administering comprises administering a tablet, a capsule, a caplet, a troche, a lozenge, an oral powder, an oral solution, an oral film, a thin strip, or an oral suspension. 
     
     
         4 . The method of  claim 1 , wherein the conjugate is administered in the form of a salt. 
     
     
         5 . The method of  4 , wherein the salt is a mesylate, a hydrochloride salt, a sulfate, an oxalate, a triflate, a citrate, a malate, a tartrate, a phosphate, a nitrate, a benzoate, an acetate, a carbonate, a hydroxide, a sodium salt, a potassium salt, a magnesium salt, a calcium salt, a zinc salt, an ammonium salt, or a mixture thereof. 
     
     
         6 . The method of  claim 1 , comprising administering a dosage form containing from about 1 mg to about 1000 mg of the conjugate, the salt thereof, or the combination thereof. 
     
     
         7 . The method of  claim 1 , comprising administering a dosage form containing from about 5 mg to about 250 mg of the conjugate, the salt thereof, or the combination thereof. 
     
     
         8 . The method of  claim 1 , comprising administering a dosage form containing from about 10 mg to about 100 mg of the conjugate, the salt thereof, or the combination thereof. 
     
     
         9 . The method of  claim 1 , wherein the conjugate, the salt thereof, or the combination thereof is in an amount sufficient to provide a therapeutically bioequivalent Area Under the Curve (AUC) when compared to amphetamine alone, but does not provide a C max  spike. 
     
     
         10 . The method of  claim 1 , wherein the conjugate, the salt thereof, or the combination thereof is in an amount sufficient to provide a therapeutically bio equivalent AUC when compared to amphetamine alone, but does not provide an equivalent C max . 
     
     
         11 . The method of  claim 1 , wherein the disorder or condition is attention deficit hyperactivity disorder, attention deficit disorder, obesity, narcolepsy, appetite suppression, depression, anxiety, wakefulness, or a combination thereof. 
     
     
         12 . The method of  claim 11 , wherein the disorder or condition is obesity. 
     
     
         13 . The method of  claim 11 , wherein the disorder or condition is appetite suppression. 
     
     
         14 . The method of  claim 11 , wherein the disorder or condition is depression. 
     
     
         15 . The method of  claim 11 , wherein the disorder or condition is narcolepsy. 
     
     
         16 . The method of  claim 11 , wherein the disorder or condition is attention deficit hyperactivity disorder. 
     
     
         17 . The method of  claim 11 , wherein the disorder or condition is attention deficit disorder. 
     
     
         18 . The method of  claim 3 , wherein the step of orally administering comprises administering an oral film. 
     
     
         19 . The method of  claim 3 , wherein the step of orally administering comprises administering a thin strip.