Delivery of benzodiazepines through an inhalation route

• US 20030032638A1
• Filed: 05/21/2002
• Published: 02/13/2003
• Est. Priority Date: 05/24/2001
• Status: Abandoned Application

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Inventors: Kim, John J., Rabinowitz, Joshua D., Zaffaroni, Alejandro C.
• Application Number:
  US10/153,313
• Publication Number:
  US 20030032638A1
• Time in Patent Office: Days
• US Class Current: 514/221
• 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 31/216 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 31/473 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 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• 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 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 benzodiazepines through an inhalation route. Specifically, it relates to aerosols containing benzodiazepines 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 a benzodiazepine. In a method aspect of the present invention, a benzodiazepine 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 a benzodiazepine, 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 a benzodiazepine through an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of a benzodiazepine; and, b) a device that forms a benzodiazepine containing aerosol from the composition, for inhalation by the mammal.

Claims

1. An aerosol for inhalation therapy, wherein the aerosol comprises particles comprising at least 10 percent by weight of a benzodiazepine, and wherein the benzodiazepine is not adinazolam, chlordiazepoxide, clobenepam, lorazepam, loprazolam, midazolam, diazepam, alprazolam, estazolam, or triazolam.

2. An aerosol for inhalation therapy, wherein the aerosol comprises particles comprising at least 10 percent by weight of clonazepam, flunitrazepam or flurazepam.

3. The aerosol according to claim 2, wherein the aerosol particles have a mass median aerodynamic diameter of less than 3 microns.

4. The aerosol according to claim 2, wherein the particles comprise less than 2.5 percent by weight of clonazepam, flunitrazepam or flurazepam degradation products.

5. The aerosol according to claim 3, wherein the aerosol comprises particles comprising at least 90 percent by weight of clonazepam, flunitrazepam or flurazepam.

6. The aerosol according to claim 5, wherein the aerosol particles have a mass median aerodynamic diameter less than 2 microns.

7. The aerosol according to claim 6, wherein the aerosol comprises particles comprising at least 97 percent by weight of clonazepam, flunitrazepam or flurazepam.

8. A method of delivering clonazepam, flunitrazepam or flurazepam to a mammal through an inhalation route, wherein the route comprises:

a) heating a composition, wherein the composition comprises at least 5 percent by weight of clonazepam, flunitrazepam or flurazepam, to form a vapor; and

,

b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles,

which is inhaled by the mammal.

9. The method according to claim 8, wherein the particles comprise at least 10 percent by weight of clonazepam, flunitrazepam or flurazepam.

10. The method according to claim 8, wherein the aerosol particles have a mass median aerodynamic diameter of less than 3 microns.

11. The method according to claim 8, wherein the particles comprise less than 2.5 percent by weight of clonazepam, flunitrazepam or flurazepam degradation products.

12. The method according to claim 10, wherein the aerosol comprises particles comprising at least 90 percent by weight of clonazepam, flunitrazepam or flurazepam.

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

14. The method according to claim 13, wherein the aerosol comprises particles comprising at least 97 percent by weight of clonazepam, flunitrazepam or flurazepam.

15. A kit for delivering clonazepam, flunitrazepam or flurazepam through an inhalation route to a mammal, wherein the kit comprises:

a) a composition comprising at least 5 percent by weight of clonazepam, flunitrazepam or flurazepam; and

,

b) a device that forms a clonazepam, flunitrazepam or flurazepam aerosol from the composition, for inhalation by the mammal

and wherein the device comprises;

a) an element for heating the clonazepam, flunitrazepam or flurazepam composition to form a vapor;

b) an element allowing the vapor to cool to form an aerosol; and

,

c) an element permitting the mammal to inhale the aerosol.