Composition and method for treating neurological disease

• US 8,987,333 B2
• Filed: 08/04/2014
• Issued: 03/24/2015
• Est. Priority Date: 11/24/2004
• Status: Active Grant

• Current Assignee: Adamas Pharma, LLC (Supernus Pharmaceuticals, Inc.)
• Original Assignee: Adamas Pharmaceuticals, Inc. (Supernus Pharmaceuticals, Inc.)
• Inventors: Went, Gregory T., Fultz, Timothy J., Porter, Seth, Meyerson, Laurence R., Burkoth, Timothy S.
• Primary Examiner(s): ZAREK, PAUL E
• Application Number:
  US14/451,262
• Publication Number:
  US 20140356425A1
• Time in Patent Office: 232 Days
• Field of Search: 514/565, 514/656
• US Class Current: 514/565
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/16 Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/5021 Organic macromolecular compounds
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs

Abstract

Disclosed are compositions comprising amantadine, or a pharmaceutically acceptable salt thereof, and one or more excipients, wherein at least one of the excipients modifies release of amantadine. Methods of administering the same are also provided.

Claims

1. An osmotic device comprising a core surrounded by a semipermeable membrane having an exit means there through wherein:

a) the core comprises a mixture of (i) a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, (ii) an osmotically active component and (iii) at least one other excipient,

b) the osmotic device further comprises an immediate release overcoat layer comprising the drug,

c) the osmotic device comprises a total of 50 mg to 500 mg of the drug, and at least 50% of the total drug is provided in the core, and

d) the osmotic device provides a mean change in amantadine plasma concentration as a function of time (dC/dT) that is less than 40% of the dC/dT provided by the same quantity of an immediate release form of the drug, wherein the dC/dT values are measured in a single dose human pharmacokinetic study over the time period between 0 and 4 hours after administration.

4. The osmotic device of any of claims 1 to 3, wherein the osmotic device comprises a total of 100 mg to 500 mg of the drug.

5. The osmotic device of any of claims 1 to 3, wherein the osmotic device comprises a total of 200 mg to 500 mg of the drug.

6. The osmotic device of any of claims 1 to 3, wherein at least 75% of the drug is provided in the core.

7. The osmotic device of any of claims 1 to 3, wherein at least 90% of the drug is provided in the core.

8. The osmotic device of any of claims 1 to 3, wherein the osmotic device provides a dC/dT that is less than 50% of the dC/dT provided by the same quantity of the drug in an immediate release form.

9. The osmotic device of any of claims 1 to 3, wherein the osmotic device provides a dC/dT that is less than 40% of the dC/dT provided by the same quantity of the drug in an immediate release form.

10. The osmotic device of any of claims 1 to 3, wherein the extent of drug bioavailability is maintained.

11. The osmotic device of any of claims 1 to 3, wherein the osmotic device provides a shift in amantadine Tmax of 2 hours to 16 hours relative to an immediate release form of amantadine, wherein the Tmax is measured in a single dose human pharmacokinetic study.

2. An osmotic device comprising a core surrounded by a semipermeable membrane having an exit means there through wherein:

a) the core comprises a mixture of (i) a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, (ii) an osmotically active component and (iii) at least one other excipient,

b) the osmotic device further comprises an immediate release overcoat layer comprising the drug,

c) the osmotic device comprises a total of 50 mg to 500 mg of the drug, and at least 50% of the total drug is provided in the core, and

d) the osmotic device provides a mean change in amantadine plasma concentration as a function of time (dC/dT) that is less than 40% of the dC/dT provided by the same quantity of an immediate release form of the drug, wherein the dC/dT values are measured in a single dose human pharmacokinetic study over the time period between administration and Tmax of the immediate release form.

3. An osmotic device comprising a core surrounded by a semipermeable membrane having an exit means there through wherein:

a) the core comprises a mixture of (i) a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, (ii) an osmotically active component and (iii) at least one other excipient,

b) the osmotic device further comprises an immediate release overcoat layer comprising the drug,

c) the osmotic device comprises a total of 50 mg to 500 mg of the drug, and at least 50% of the total drug is provided in the core, and

d) the osmotic device provides a mean change in amantadine plasma concentration as a function of time (dC/dT) that is less than 40% of the dC/dT provided by the same quantity of an immediate release form of the drug, wherein the dC/dT of the osmotic device is measured in a single dose human pharmacokinetic study over the time period between 2 hours and 4 hours after administration and the dC/dT provided by the same quantity of the drug in an immediate release form is measured in a single dose human pharmacokinetic study over the time period between administration and Tmax of the immediate release form.