Delivery of rizatriptan and zolmitriptan through an inhalation route

• US 6,759,029 B2
• Filed: 05/22/2002
• Issued: 07/06/2004
• Est. Priority Date: 05/24/2001
• Status: Expired due to Fees

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Molecular Delivery Corporation (Grupo Ferrer Internacional SA)
• Inventors: Hale, Ron L., Solas, Dennis W., Rabinowitz, Joshua D., Zaffaroni, Alejandro C.
• Primary Examiner(s): Hartley, Michael G.
• Assistant Examiner(s): Haghighatian, Mina
• Application Number:
  US10/155,621
• Publication Number:
  US 20030005925A1
• Time in Patent Office: 776 Days
• Field of Search: 424/45, 424/46, 514/220, 514/414, 128/200.14, 128/203.15, 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 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• 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 31/422 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 31/49 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: 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 rizatriptan or zolmitriptan through an inhalation route. Specifically, it relates to aerosols containing rizatriptan or zolmitriptan that are used in inhalation therapy. In a composition aspect of the present invention, the aerosol comprises particles comprising at least 5 percent by weight of rizatriptan or zolmitriptan. In a method aspect of the present invention, either rizatriptan or zolmitriptan is delivered to a mammal through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises at least 5 percent by weight of rizatriptan or zolmitriptan, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles, which is inhaled by the mammal. In a kit aspect of the present invention, a kit for delivering rizatriptan or zolmitriptan through an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of rizatriptan or zolmitriptan; and, b) a device that forms a rizatriptan or zolmitriptan containing aerosol from the composition, for inhalation by the mammal.

Claims

1. A composition for delivery of rizatriptan or zolmitriptan comprising a condensation aerosol

a) formed by volatilizing rizatriptan or zolmitriptan under conditions effective to produce a heated vapor of the rizatriptan or zolmitriptan and condensing the heated vapor of the rizatriptan or zolmitriptan to form condensation aerosol particles,

b) wherein said condensation aerosol particles are characterized by less than 5% rizatriptan or zolmitriptan degradation products, and

c) wherein the aerosol MMAD is less than 3 microns.

2. The composition according to claim 1, wherein the mass of the condensation aerosol is at least 0.10 mg.

3. The composition according to claim 1, wherein the aerosol condensation particles are characterized by less than 2.5 percent by weight of rizatriptan or zolmitriptan degradation products.

4. The composition according to claim 1, wherein the condensation aerosol particles comprise at least 90 percent by weight of rizatriptan or zolmitriptan.

5. The composition according to claim 4, wherein the condensation aerosol has a mass median aerodynamic diameter less than 2 microns.

6. The composition according to claim 5, wherein the condensation aerosol particles comprise at least 97 percent by weight of rizatriptan or zolmitriptan.

7. A method of producing rizatriptan or zolmitriptan in an aerosol form comprising:

a) volatilizing rizatriptan or zolmitriptan under conditions effective to produce a heated vapor of rizatriptan or zolmitriptan, and

b) during said volatilizing, passing air through the heated vapor to produce aerosol particles of rizatriptan or zolmitriptan comprising less than 5% rizatriptan or zolmitriptan degradation products and an aerosol having an MMAD less than 3 μ

m.

8. The method according to claim 7, wherein the aerosol particles are formed at a rate of greater than 0.5 mg/sec.

9. The method according to claim 7, wherein the mass of the aerosol is at least 0.10 mg.

10. The method according to claim 7, wherein said volatilizing includes heating a thin layer which includes the rizatriptan or zolmitriptan and which is on a solid support having the surface texture of a metal foil, to a temperature sufficient to volatilize the rizatriptan or zolmitriptan from the thin layer.

11. The method according to claim 7, wherein the particles comprise less than 2.5 percent by weight of rizatriptan or zolmitriptan degradation products.

12. The method according to claim 7, wherein the aerosol particles comprise at least 90 percent by weight of rizatriptan or zolmitriptan.

13. The method according to claim 12, wherein the aerosol has a mass median aerodynamic diameter less than 2 microns.

14. The method according to claim 13, wherein the aerosol particles comprise at least 97 percent by weight of rizatriptan or zolmitriptan.