Sustained release aminopyridine composition

• US 20050276851A1
• Filed: 12/13/2004
• Published: 12/15/2005
• Est. Priority Date: 12/11/2003
• Status: Active Grant

• Current Assignee: Acorda Therapeutics Incorporated
• Original Assignee: Acorda Therapeutics Incorporated
• Inventors: Cunningham, Sean, Blight, Andrew R.
• Granted Patent: US 8,007,826 B2
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4409 only substituted in position 4, e.g. isoniazid, iproniazid
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• 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: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A pharmaceutical composition which comprises a therapeutically effective amount of a aminopyridine dispersed in a release matrix, including, for example, a composition that can be formulated into a stable, sustained-release oral dosage formulation, such as a tablet which provides, upon administration to a patient, a therapeutically effective plasma level of the aminopyridine for a period of at least 12 hours, preferably 24 hours or more and the use of the composition to treat various neurological diseases.

Claims

1. A sustained release tablet comprising:

a sustained release matrix and an aminopyridine, said tablet exhibiting a release profile to obtain a C_max;

C_τ

ratio in vivo of about 1.0 to about 3.5 and a predetermined C_avSS.

2. The sustained release tablet of claim 1 wherein said C_max:

C_τ

ratio is about 1.5 to about 3.0.

3. The sustained release tablet of claim 1 wherein said predetermined C_avSS is about 21 ng/ml.

4. The sustained release tablet of claim 1 wherein said predetermined C_avSS is about 31 ng/ml.

5. The sustained release tablet of claim 1 wherein said predetermined C_avSS is about 40 ng/ml.

6. The sustained release tablet of claim 1 wherein said C_max:

C_τ

ratio is about 2.0 to about 3.0.

7. The sustained release tablet of claim 1 wherein said aminopyridine is 4-aminopyridine.

8. The sustained release table of claim 1 wherein said sustained release matrix is hydroxypropylmethylcellulose.

9. A method of treating a disease associated with a neurological disorder, said method comprising:

administering an aminopyridine on a dosing regimen to obtain an in vivo C_max;

C_τ

ratio of 1.0 to 3.5 and a CavSS of about 15 ng/ml to about 35 ng/ml.

10. The method of claim 9 wherein said C_max:

C_τ

ratio is about 1.5 to about 3.0.

11. The method of claim 9 wherein said C_max:

C_τ

ratio is about 2.0 to about 3.0.

12. The method of claim 9 wherein said neurological disorder comprises a spinal cord injury, Alzheimer'"'"'s disease, multiple sclerosis, or amyotrophic lateral sclerosis.

13. The method of claim 9 wherein said neurological disorder comprises a spinal cord injury.

14. The method of claim 9 wherein said neurological disorder comprises multiple sclerosis.

15. The method of claim 9 wherein said dosing regimen is comprised of administering a tablet twice daily.

16. The method of claim 15 wherein said twice daily administration comprises every twelve hours.

17. The method of claim 9 wherein said aminopyridine comprises 4-aminopyridine.

18. A therapeutic composition comprised of a release matrix and an active aminopyridine, said aminopyridine being released from said release matrix at a rate to maintain an in vivo C_max:

C_τ

ratio of 1.0 to 3.5 and a C_avSS of about 15 ng/ml to about 35 ng/ml.

22. The therapeutic composition of claim 22 wherein the release matrix is hydroxypropylmethylcellulose.

19. The therapeutic composition of claim 22 wherein said C_max:

C_τ

ratio is about 1.5 to about 3.0.

20. The therapeutic composition of claim 22 wherein said C_max:

C_τ

ratio is about 2.0 to about 3.0.

21. The therapeutic composition of claim 22 wherein the active aminopyridine is 4-aminopyridine.

23. A sustained release composition comprising:

a sustained release matrix and an aminopyridine, wherein said composition provides a C_avSS of about 15 ng/ml to about 35 ng/ml.