Delivery of compounds for the treatment of migraine through an inhalation route

• US 7,045,118 B2
• Filed: 01/27/2004
• Issued: 05/16/2006
• Est. Priority Date: 05/24/2001
• Status: Expired due to Term

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Inventors: Rabinowitz, Joshua D., Zaffaroni, Alejandro C.
• Primary Examiner(s): Low, Christopher S. F.
• Assistant Examiner(s): Haghighatian, Mina
• Application Number:
  US10/766,574
• Publication Number:
  US 20040191180A1
• Time in Patent Office: 840 Days
• Field of Search: 424/45, 424/43, 424/46, 424/434, 424/489, 424/499, 514/220, 514/414, 514/958, 128/200.14, 128/200.24
• US Class Current: 424/45
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/421 1,3-Oxazoles, e.g. pemoline, trimethadione
• CPC Class Codes: A61K 31/422 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/423 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/473 ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/49 Cinchonan derivatives, e.g. quinine
• CPC Class Codes: A61K 31/495 : having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/496 : Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/4985 : Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/501 : not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/519 : ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/53 : having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61K 31/551 : having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/5517 : condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
• CPC Class Codes: A61K 47/54 : the modifying agent being an organic compound
• CPC Class Codes: A61K 9/007 : Pulmonary tract; Aromatherapy
• 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 9/12 : Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• CPC Class Codes: A61M 11/042 : electrical
• CPC Class Codes: A61M 15/06 : Inhaling appliances shaped like cigars, cigarettes or pipes
• CPC Class Codes: A61M 2205/8206 : battery-operated
• CPC Class Codes: A61P 15/10 : for impotence
• CPC Class Codes: A61P 21/02 : Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 : Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 : Anxiolytics
• CPC Class Codes: A61P 25/24 : Antidepressants
• CPC Class Codes: A61P 25/32 : Alcohol-abuse
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: F24V 30/00 : Apparatus or devices using heat produced by exothermal chemical reactions other than combustion

Abstract

The present invention relates to the delivery of a migraine headache drug through an inhalation route. Specifically, it relates to aerosols containing a migraine headache drug that are used in inhalation therapy. In a method aspect of the present invention, a migraine headache drug is administered to a patient through an inhalation route. The method comprises: a) heating a thin layer of a migraine headache drug, on a solid support to form a vapor; and, b) passing air through the heated vapor to produce aerosol particles having less than 5% drug degradation products. In a kit aspect of the present invention, a kit for delivering a migraine headache drug through an inhalation route is provided which comprises: a) a thin coating of an a migraine drug composition and b) a device for dispensing said thin coating as a condensation aerosol.

Claims

1. A condensation aerosol for delivery of a drug selected from the group consisting of rizatriptan, zolmitriptan, sumatriptan, frovatriptan and naratriptan,

wherein the condensation aerosol is formed by heating a thin layer containing the drug, on a solid support, to produce a vapor of the drug, and condensing the vapor to form a condensation aerosol

characterized by less than 10% drug degradation products by weight, and

an MMAD of less than 5 microns.

2. The condensation aerosol according to claim 1, wherein the condensation aerosol is formed at a rate greater than 10⁹ particles per second.

3. The condensation aerosol according to claim 2, wherein the condensation aerosol is formed at a rate greater than 10¹⁰ particles per second.

4. The condensation aerosol according to claim 1, wherein said condensation aerosol is characterized by less than 2.5% drug degradation products by weight.

8. The condensation aerosol according to claim 1, wherein the condensation aerosol is characterized by an MMAD of 0.1 to 5 microns.

9. The condensation aerosol according to claim 1, wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.

10. The condensation aerosol according to claim 9, wherein the condensation aerosol is characterized by an MMAD of about 0.2 to 3 microns.

11. The condensation aerosol according to claim 1, wherein the condensation aerosol is characterized by less than 5% drug degradation products by weight.

12. The condensation aerosol according to claim 1, wherein the thin layer has a thickness between 0.7 and 5.0 microns.

13. The condensation aerosol according to claim 1, wherein the solid support is a metal foil.

5. A method of producing a drug selected from the group consisting of rizatriptan, zolmitriptan, sumatriptan, frovatriptan and naratriptan in an aerosol form comprising:

a. heating a thin layer containing the drug, on a solid support, to produce a vapor of the drug, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 10% drug degradation products by weight, and an MMAD of less than 5 microns.

6. The method according to claim 5, wherein the condensation aerosol is formed at a rate greater than 10⁹ particles per second.

7. The method according to claim 6, wherein the condensation aerosol is formed at a rate of greater than 10¹⁰ particles per second.

14. The method according to claim 6, wherein the condensation aerosol is characterized by an MMAD of 0.2 to 5 microns.

15. The method according to claim 5, wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.

16. The method according to claim 5, wherein the condensation aerosol is characterized by an MMAD of about 0.2 to about 3 microns.

17. The method according to claim 5, wherein the condensation aerosol is characterized by less than 5% drug degradation products by weight.

18. The method according to claim 17, wherein the condensation aerosol is characterized by less than 2.5% drug degradation products by weight.

19. The method according to claim 5, wherein the thin layer has a thickness between 0.7 and 5.0 microns.

20. The method according to claim 16, wherein the solid support is a metal foil.

21. A condensation aerosol for delivery of rizatriptan, wherein the condensation aerosol is formed by heating a thin layer containing rizatriptan, on a solid support, to produce a vapor of rizatriptan, and condensing the vapor to form a condensation aerosol characterized by less than 5% rizatriptan degradation products by weight, and an MMAD of about 0.2 to 3 microns.

22. A condensation aerosol for delivery of zolmitriptan, wherein the condensation aerosol is formed by heating a thin layer containing zolmitriptan, on a solid support, to produce a vapor of zolmitriptan, and condensing the vapor to form a condensation aerosol characterized by less than 5% zolmitriptan degradation products by weight, and an MMAD of about 0.2 to 3 microns.

23. A condensation aerosol for delivery of sumatriptan, wherein the condensation aerosol is formed by heating a thin layer containing sumatriptan, on a solid support, to produce a vapor of sumatriptan, and condensing the vapor, to form a condensation aerosol characterized by less than 5% sumatriptan degradation products by weight, and an MMAD of about 0.2 to 3 microns.

24. A condensation aerosol for delivery of frovatriptan, wherein the condensation aerosol is formed by heating a thin layer containing frovatriptan, on a solid support, to produce a vapor of frovatriptan, and condensing the vapor to form a condensation aerosol characterized by less than 5% frovatriptan degradation products by weight, and an MMAD of about 0.2 to 3 microns.

25. A condensation aerosol for delivery of naratriptan, wherein the condensation aerosol is formed by heating a thin layer containing naratriptan, on a solid support, to produce a vapor of naratriptan, and condensing the vapor to form a condensation aerosol characterized by less than 5% naratriptan degradation products by weight, and an MMAD of about 0.2 to 3 microns.

26. A method of producing rizatriptan in an aerosol form comprising:

a. heating a thin layer containing rizatriptan, on a solid support, to produce a vapor of rizatriptan, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% rizatriptan degradation products by weight, and an MMAD of about 0.2 to 3 microns.

27. A method of producing zolmitriptan in an aerosol form comprising:

a. heating a thin layer containing zolmitriptan, on a solid support, to produce a vapor of zolmitriptan and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% zolmitriptan degradation products by weight, and an MMAD of about 0.2 to 3 microns.

28. A method of producing sumatriptan in an aerosol form comprising:

a. heating a thin layer containing sumatriptan, on a solid support, to produce a vapor of sumatriptan, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% sumatriptan degradation products by weight, and an MMAD of about 0.2 to 3 microns.

29. A method of producing frovatriptan in an aerosol form comprising:

a. heating a thin layer containing frovatriptan, on a solid support, to produce a vapor of frovatriptan, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% frovatriptan degradation products by weight, and an MMAD of about 0.2 to 3 microns.

30. A method of producing naratriptan in an aerosol form comprising:

a. heating a thin layer containing naratriptan, on a solid support, to produce a vapor of naratriptan, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% naratriptan degradation products by weight, and an MMAD of about 0.2 to 3 microns.