Chronic, Bolus Adminstration Of D-Threo Methylphenidate

• US 20090088455A1
• Filed: 12/09/2008
• Published: 04/02/2009
• Est. Priority Date: 12/04/1995
• Status: Abandoned Application

• Current Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Original Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Inventors: Zeldis, Jerome B., Zeitlin, Andrew L., Dariani, Maghsoud M.
• Application Number:
  US12/331,127
• Publication Number:
  US 20090088455A1
• Time in Patent Office: Days
• US Class Current: 514/317
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61K 9/2886 having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C07D 211/34 with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C12P 17/12 containing a six-membered hetero ring
• CPC Class Codes: C12P 41/006 by reactions involving C-N bonds, e.g. nitriles, amides, hydantoins, carbamates, lactames, transamination reactions, or keto group formation from racemic mixtures

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.

Claims

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.