Delivery of antiemetics through an inhalation route

• US 6,780,400 B2
• Filed: 05/17/2002
• Issued: 08/24/2004
• Est. Priority Date: 05/24/2001
• Status: Expired due to Term

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Molecular Delivery Corporation (Grupo Ferrer Internacional SA)
• Inventors: Rabinowitz, Joshua D., Zaffaroni, Alejandro C.
• Primary Examiner(s): Hartley, Michael G.
• Assistant Examiner(s): Haghighatian, M.
• Application Number:
  US10/150,591
• Publication Number:
  US 20030021753A1
• Time in Patent Office: 830 Days
• Field of Search: 424/45, 424/46, 424/43, 424/789, 128/200.24, 128/203.15, 128/200.14, 514/220, 514/255
• 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 antiemetics through an inhalation route. Specifically, it relates to aerosols containing antiemetics 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 an antiemetic. In a method aspect of the present invention, an antiemetic 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 an antiemetic, 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 an antiemetic through an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of an antiemetic; and, b) a device that forms an antiemetic aerosol from the composition, for inhalation by the mammal.

Claims

1. A composition for delivery of an antiemetic comprising a condensation aerosol

a) formed by volatilizing an antiemetic under conditions effective to produce a heated vapor of the antiemetic and condensing the heated vapor of the antiemetic to form condensation aerosol particles;

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

c) the aerosol has an MMAD less than 3 microns.

2. A composition for delivery dolasetron, granisetron or metoclopramide comprising a condensation aerosol

a) formed by volatilizing dolasetron, granisetron or metoclopramide under conditions effective to produce a heated vapor of dolasetron, granisetron or metoclopramide and condensing the heated vapor of the dolasetron, granisetron or metoclopramide to form condensation aerosol particles;

b) wherein said condensation aerosol particles are characterized by less than 5% dolasetron, granisetron or metoclopramide degradation products, and

c) the aerosol has an MMAD less than 3 microns.

3. The composition according to claim 2, wherein the condensation aerosol particles comprise less than 2.5 percent by weight of dolasetron, granisetron or metoclopramide degradation products.

4. The composition according to claim 2, wherein the aerosol particles comprise at least 95percent by weight of dolasetron, granisetron or metoclopramide.

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

6. The composition according to claim 5, wherein the aerosol particles comprise at least 97 percent by weight of dolasetron, granisetron or metoclopramide.

7. A method of producing dolasetron, granisetron or metoclopramide in an aerosol form comprising:

a) volatilizing dolasetron, granisetron or metoclopramide under conditions effective to produce a heated vapor of the drug, and

b) during said volatilizing, passing air through the heated vapor to produce aerosol particles of the dolasetron, granisetron or metoclopramide comprising less than 5% dolasetron, granisetron or metoclopramide degradation products and an aerosol having an MMAD less than 3 microns.

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 said volatilizing includes heating a thin layer comprising dolasetron, granisetron or metoclopramide on a solid support having the surface texture of a metal foil, to a temperature sufficient to volatilize dolasetron, granisetron or metoclopramide from the thin layer.

10. The method according to claim 7, wherein the aerosol particles comprise less than 2.5 percent by weight of dolasetron, granisetron or metoclopramide degradation products.

11. The method according to claim 9, wherein the aerosol particles comprise at least 95 percent by weight of dolasetron, granisetron or metoclopramide.

12. The method according to claim 11, wherein the aerosol has a mass median aerodynamic diameter less than 2 microns.

13. The method according to claim 12, wherein the aerosol particles comprise at least 97 percent by weight of dolasetron, granisetron or metoclopramide.

14. A method of producing an antiemetic in an aerosol form comprising:

a) volatilizing an antiemetic under conditions effective to produce a heated vapor of the antiemetic, and

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