Delivery of rizatriptan or zolmitriptan through an inhalation route

• US 7,018,621 B2
• Filed: 03/03/2004
• Issued: 03/28/2006
• Est. Priority Date: 05/24/2001
• Status: Expired due to Fees

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Inventors: Hale, Ron L., Rabinowitz, Joshua D., Solas, Dennis W., Zaffaroni, Alejandro C.
• Primary Examiner(s): Padmanabhan, Sreeni
• Assistant Examiner(s): Haghighatian, Mina
• Application Number:
  US10/792,012
• Publication Number:
  US 20040170570A1
• Time in Patent Office: 755 Days
• Field of Search: 424/45, 424/46, 424/43, 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 31/192 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 compounds for the treatment of migraine and headache through an inhalation route. Specifically, it relates to aerosols containing rizatriptan or zolmitriptan that are used in inhalation therapy. In a method aspect of the present invention, rizatriptan or zolmitriptan is administered to a patient through an inhalation route. The method comprises: a) heating a thin layer of rizatriptan or zolmitriptan 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 rizatriptan or zolmitriptan through an inhalation route is provided which comprises: a) a thin coating of a rizatriptan or zolmitriptan composition; and, b) a device for dispending said thin coating as a condensation aerosol.

Claims

1. A dose form of rizatriptan comprising a condensation aerosol

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 10% rizatriptan degradation products by weight, and

an MMAD of less than 5 microns, wherein the dose form comprises less than 4 mg of rizatriptan.

2. A dose form of zolmitriptan comprising a condensation aerosol

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 10% zolmitriptan degradation products by weight, and

an MMAD of less than 5 microns, wherein the dose form comprises less than 1 mg zolmitriptan.

3. A method of producing a dose form of rizatriptan comprising a condensation aerosol, the method 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 10% rizatriptan degradation products by weight, and an MMAD of less than 5 microns, wherein the dose form comprises less than 4 mg of rizatriptan.

4. A method of producing a dose form of zolmitriptan comprising a condensation aerosol, the method 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 10% zolmitriptan degradation products by weight, and an MMAD of less than 5 microns, wherein the dose form comprises less than 1 mg of zolmitriptan.

5. 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 N-oxide or didehydro rizatriptan by weight, and an MMAD of less than 5 microns.

6. 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 N-oxide or didehydro zolmitriptan by weight, and an MMAD of less than 5 microns.

7. 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 thorough the vapor to form a condensation aerosol characterized by less than 5% rizatriptan N-oxide or didehydro rizatriptan by weight, and an MMAD of less than 5 microns.

8. 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 thorough the vapor to form a condensation aerosol characterized by less than 5% zolmitriptan N-oxide or didehydro zolmitriptan by weight, and an MMAD of less than 5 microns.