Chronic, Bolus Adminstration Of D-Threo Methylphenidate

Abstract

Chronic bolus administration of D-threo methylphenidate is provided. The administration of the D-threo isomer eliminates adverse side effects associated with the DL racemate, and provides improved effectiveness. The compositions and methods of the invention are useful in treating nervous system disorders including attention deficit disorder, attention deficit hyperactivity disorder, and cognitive decline associated with systemic diseases such as acquired immunodeficiency syndrome.

1 . A drug dosage form for the bolus parenteral administration of a methylphenidate drug comprising an injectable composition comprising D-threo-methylphenidate or pharmaceutically acceptable salt thereof in an amount sufficient for daily effectiveness for the treatment of a nervous disorder. 
   
   
       2 . The drug dosage form of  claim 1  that is substantially free of L-threo-methylphenidate. 
   
   
       3 . The dosage form of  claim 1  wherein the administration is subcutaneous, intravenous, intramuscular, or interperitoneal. 
   
   
       4 . The dosage form of  claim 1  wherein the administration is via a pharmaceutical carrier selected from the group consisting of a sterile liquid or mixture of liquids, an alcohol, glycols, glycerol ketals, and ethers. 
   
   
       5 . The dosage form of  claim 4  wherein said sterile liquid or mixture of liquids is water, saline, aqueous dextrose, or related sugar solutions. 
   
   
       6  The dosage form of  claim 4  wherein said alcohol is ethanol. 
   
   
       7 . The dosage form of  claim 4  wherein said glycols are propylene glycol or polyethylene glycol. 
   
   
       8 . The dosage form of  claim 4  wherein said glycerol ketal is 2,2-dimethyl-1,3-dioxolane-4-methanol. 
   
   
       9 . The dosage form of  claim 5  wherein said ether is poly(ethyleneglycol)400, oils, fatty acids, fatty acid esters, or glycerides. 
   
   
       10 . The dosage form of  claim 9  further comprising at least one pharmaceutically acceptable surfactant, a suspending agent, an emulsifying agent, or other pharmaceutically acceptable adjuvants. 
   
   
       11 . The dosage form of  claim 10  wherein said surfactant is a soap, detergent, or mixture of detergents. 
   
   
       12 . The dosage form of  claim 10  wherein said suspending agent is pectin, carbomers, methylcellulose, hydroxypropylmethylcellulose, or carboxymethylcellulose. 
   
   
       13 . The dosage form of  claim 9  wherein said oils are selected from the group consisting of petroleum, animal, vegetable, or synthetic oils. 
   
   
       14 . The dosage form of  claim 13  wherein said oils are peanut oil, soybean oil, sesame oil, cottonseed oil, corn oil, olive oil, petrolatum, or mineral oil. 
   
   
       15 . The dosage form of  claim 9  wherein said fatty acids are selected from the group consisting of oleic acid, stearic acid, and isostearic acid. 
   
   
       16 . The dosage form of  claim 9  wherein said fatty acid esters are selected from the group consisting of ethyl oleate and isopropyl myristate. 
   
   
       17 . The dosage form of  claim 11  wherein said soap is alkaline metal, ammonium and triethanolamine salts of fatty acids. 
   
   
       18 . The dosage form of  claim 11  wherein said detergent is selected from the group consisting of cationic detergents, anionic detergents, nonionic detergents, and amphoteric detergents. 
   
   
       19 . The dosage form of  claim 18  wherein said detergent is dimethyl dialkyl ammonium halides, alkyl pyridinium halides, alkyl, aryl and olefin sulfonates, monoglyceride sulfates, sulfasucciantes, fatty amine oxides, fatty acid alkanolamides, polyoxyethylenepropylene copolymers, alkyl-aminopropoionates, or 2-alkylimidazoline quaternary ammonium salts. 
   
   
       20 . The dosage form of  claim 1  wherein said amount is 0.01% by weight of D-threo-methylphenidate or salt thereof. 
   
   
       21 . The dosage form of  claim 1  further comprising a viscosity increasing substance selected from the group consisting of sodium carboxymethylcellulose, sorbitol, dextran, and stabilizers. 
   
   
       22 . The dosage form of  claim 10  wherein said surfactant has a hydrophile-lipophile balance (HLB) of about 12 to about 17. 
   
   
       23 . The dosage form of  claim 10  wherein said surfactant is about 5% to about 15% by weight of the dosage form. 
   
   
       24 . The dosage form of  claim 10  wherein said surfactant is selected from the group consisting of polyethene sorbitan fatty acid esters. 
   
   
       25 . The dosage form of  claim 24  wherein the surfactant is sorbitan monooleate.