Triptan powders for pulmonary delivery

• US 10,034,857 B2
• Filed: 07/01/2016
• Issued: 07/31/2018
• Est. Priority Date: 07/02/2015
• Status: Active Grant

• Current Assignee: Civitas Therapeutics, Inc. (Acorda Therapeutics Incorporated)
• Original Assignee: Civitas Therapeutics, Inc. (Acorda Therapeutics Incorporated)
• Inventors: Lipp, Michael M.
• Primary Examiner(s): Henley, III, Raymond J
• Application Number:
  US15/200,335
• Publication Number:
  US 20170000765A1
• Time in Patent Office: 760 Days
• Field of Search: 514415
• CPC Class Codes: A61K 31/4045 Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
• 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 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61P 25/06 Antimigraine agents

Abstract

The invention provides stable, spray-dried, particle formulations containing a triptan, preferably sumatriptan, or a pharmaceutically acceptable salt thereof, which are useful for pulmonary administration to the respiratory tract of a patient for the treatment of disease.

Claims

1. A pharmaceutical composition for pulmonary delivery to the respiratory tract of a patient comprising spray-dried particles comprising a triptan or a pharmaceutically salt thereof and a phospholipid, wherein the triptan or salt thereof is present in the particles (a) in crystalline form or (b) in both crystalline and amorphous forms.

2. The pharmaceutical composition of claim 1, wherein the triptan is sumatriptan or a pharmaceutically acceptable salt thereof.

3. The pharmaceutical composition of claim 2, wherein the triptan is sumatriptan succinate.

4. The pharmaceutical composition of claim 1, wherein the triptan is sumatriptan free base.

5. The pharmaceutical composition of claim 1, wherein the spray-dried particles further comprise a salt, an amino acid or a sugar.

6. The pharmaceutical composition of claim 1, wherein the particles comprise sumatriptan or a pharmaceutically acceptable salt thereof in crystalline form.

7. The pharmaceutical composition of claim 1, wherein the particles comprise sumatriptan or a pharmaceutically acceptable salt thereof in both crystalline and amorphous forms.

8. The pharmaceutical composition of claim 1, wherein the particles comprise sumatriptan or a pharmaceutically acceptable salt thereof, DPPC, sodium chloride and maltodextrin.

9. The pharmaceutical composition of claim 1, wherein the particles comprise sumatriptan or a pharmaceutically acceptable salt thereof, DPPC, sodium chloride and 1-leucine.

10. The pharmaceutical composition of claim 1, wherein the particles comprise 5 to 50% triptan or a pharmaceutically acceptable salt thereof, 5-20% phospholipid, and 1-10% sodium chloride as measured by percent of dry solids in the powder.

11. The pharmaceutical composition of claim 1, wherein the particles comprise 25 to 55% triptan or a pharmaceutically acceptable salt thereof, 5-20% phospholipid, 1-10% sodium chloride and 25 to 60% of an excipient selected from maltodextrins, lactose, glycine, trehalose, mannitol and 1-leucine, as measured by percent of dry solids in the powder.

12. The pharmaceutical composition of claim 11, wherein the triptan is sumatriptan free base or a sumatriptan salt.

13. The pharmaceutical composition of claim 12, wherein the particles comprise 25 to 55% sumatriptan free base, 15-20% phospholipid, 1-5% sodium chloride and 25 to 55% of an excipient selected from maltodextrins, and 1-leucine, as measured by percent of dry solids.

14. The pharmaceutical composition of claim 13, wherein the particles comprise 30 to 50% sumatriptan free base, about 18% phospholipid, about 2% sodium chloride and 30 to 50% of an excipient selected from maltodextrins or 1-leucine as measured by percent of dry solids.

15. The pharmaceutical composition of claim 14, wherein the phospholipid is DPPC.

16. The pharmaceutical composition of claim 14 wherein the maltodextrin is (i) maltodextrin with D.E.=10.7 or (ii) SD-30.

17. The pharmaceutical composition of claim 14 comprising 1-leucine.

20. A method of delivering sumatriptan or a salt thereof to the pulmonary system of a patient comprising the steps of:

a) providing a pharmaceutical composition of claim 1 in a compartment and an inhaler to a patient;

b) dispersing the particles by breath actuation of the patient; and

c) delivering the particles to the patient'"'"'s respiratory system.

21. A method of treating migraine in a subject in need thereof, comprising administering to the pulmonary system of the subject a therapeutically effective amount of the pharmaceutical composition of claim 1.

22. A method of treating cluster headache in a subject in need thereof, comprising administering to the pulmonary system of the subject a therapeutically effective amount of the powder formulation of claim 1.

18. A powder formulation for pulmonary delivery to the respiratory tract of a patient, said powder comprising particles having a composition selected from the table below, as measured by weight percent of dry solids in the powder:

19. A powder formulation for pulmonary delivery to the respiratory tract of a patient, said powder comprising particles having a composition selected from the table below, as measured by weight percent of dry solids in the powder: