Capsules containing high doses of levodopa for pulmonary use

• US 8,545,878 B1
• Filed: 11/16/2012
• Issued: 10/01/2013
• Est. Priority Date: 11/09/2012
• Status: Active Grant

• Current Assignee: Civitas Therapeutics, Inc. (Acorda Therapeutics Incorporated)
• Original Assignee: Civitas Therapeutics, Inc. (Acorda Therapeutics Incorporated)
• Inventors: Lipp, Michael M., Batycky, Richard P., Kee, Kevin, Penachio, Ernest D., Kamerkar, Abhijit
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Tcherkasskaya, Olga V
• Application Number:
  US13/679,245
• Time in Patent Office: 319 Days
• Field of Search: None
• US Class Current: 424/451
• 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 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• 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 9/4816 Wall or shell material
• CPC Class Codes: A61K 9/485 Inorganic compounds
• CPC Class Codes: A61K 9/4858 Organic compounds

Abstract

The present invention provides a capsule containing an inhalable powder composition wherein the composition comprises about 75% by weight or more levodopa, dipalmitoylphosphatidylcholine (DPPC) and a salt characterized by a working density of less than about 100 g/L. The invention further provides a capsule containing an inhalable powder composition wherein the composition comprises about 75% by weight or more levodopa, dipalmitoylphosphatidylcholine (DPPC) and a salt characterized by a working density of less than about 100 g/L wherein the capsule material comprises hydroxypropylmethylcellulose (HPMC) and titanium dioxide.

Claims

1. A capsule for use in an inhalation device filled with a dry powder comprising levodopa and having a working density between about 0.02 to about 0.1 g/cm³, and containing a capsule shell comprising hydroxypropyl methylcellulose (HPMC) and titanium dioxide, and

wherein said capsule emits more powder comprising levodopa upon actuation of the inhalation device as compare to a capsule that comprises HPMC and is free of titanium dioxide.

2. The capsule of claim 1, wherein said working density is between about 0.02 g/cm³ to about 0.05 g/cm³.

3. The capsule of claim 1, wherein said dry powder comprises from about 2 to about 8% of water by weight.

4. The capsule of claim 3, wherein said dry powder comprises from about 5 to about 6% of water by weight.

5. The capsule of claim 1, wherein said capsule is a 00 size capsule.

6. The capsule of claim 5, wherein said dry powder comprises between about 15 and 50 milligrams of levodopa.

7. The capsule of claim 6, wherein said dry powder comprises between about 25 and 35 milligrams of levodopa.

8. The capsule of claim 1, wherein said dry powder further comprises a salt.

9. The capsule of claim 8, wherein said salt is sodium chloride.

10. The capsule of claim 8, wherein said dry powder further comprises a phospholipid.

11. The capsule of claim 10, wherein said phospholipid is dipalmitoylphosphatidylcholine (DPPC).

12. The capsule of claim 1 comprising from about 25 to 45 milligrams of dry powder comprising at least 80% of levodopa by weight, a fine particle fraction (FPF) between 55 to 68% of the nominal dose, and a working density between about 0.02 to about 0.05 g/cm³.

13. The capsule of claim 1, wherein the dry powder comprises about 85% by weight or more of levodopa.

14. The capsule of claim 1, wherein the dry powder comprises about 90% by weight or more of levodopa.

15. The capsule of claim 1, wherein the dry powder comprises a salt and the salt is sodium chloride (NaCl).

16. The capsule of claim 1, wherein the FPF of the dry powder is about 50% to about 70% of the nominal dose.

17. The capsule of claim 1, wherein the capsule is filled with about 20 milligrams or more of the dry powder.

18. The capsule of claim 1, wherein the capsule is filled with about 30 to about 50 milligrams of dry powder.

19. The capsule of claim 1, wherein the dry powder composition comprises a weight ratio of levodopa/DPPC/NaCl of 90:

8;

2.

20. The capsule of claim 1, wherein the dry powder comprises about 75% by weight or more levodopa, DPPC and a salt.

21. The capsule of claim 1, wherein the FPF of the dry powder is about 50% to about 70% of the nominal dose.