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

• US 20040185008A1
• Filed: 04/01/2004
• Published: 09/23/2004
• Est. Priority Date: 05/24/2001
• Status: Active Grant

• 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.
• Granted Patent: US 7,052,680 B2
• Time in Patent Office: Days
• US Class Current: 424/46
• 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 antiparkinsons drugs through an inhalation route. In a method aspect of the present invention, an antiparkinsons drug is administered to a patient through an inhalation route. The method comprises: a) heating a thin layer of an antiparkinsons 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 an antiparkinsons drug through an inhalation route is provided which comprises: a) a thin coating of a an antiparkinsons drug composition; and, b) a device for dispending said thin coating as a condensation aerosol.

Claims

1. A composition for delivery of benzotropine consisting of a condensation aerosol

a) formed by volatilizing a thin layer of benzotropine on a solid support, having the surface texture of a metal foil, to a temperature sufficient to produce a heated vapor of benzotropine and condensing the heated vapor of benzotropine to form condensation aerosol particles,

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

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

2. The composition according to claim 1, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

3. The composition according to claim 2, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

4. The composition according to claim 1, wherein said condensation aerosol particles are characterized by less than 2.5% benzotropine degradation products.

5. A composition for delivery of pergolide consisting of a condensation aerosol

a) formed by volatilizing a thin layer of pergolide on a solid support, having the surface texture of a metal foil, to a temperature sufficient to produce a heated vapor of pergolide and condensing the heated vapor of pergolide to form condensation aerosol particles,

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

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

6. The composition according to claim 5, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

7. The composition according to claim 6, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

8. The composition according to claim 5, wherein said condensation aerosol particles are characterized by less than 2.5% pergolide degradation products.

9. A composition for delivery of amantadine consisting of a condensation aerosol

a) formed by volatilizing a thin layer of amantadine on a solid support, having the surface texture of a metal foil, to a temperature sufficient to produce a heated vapor of amantadine and condensing the heated vapor of amantadine to form condensation aerosol particles,

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

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

10. The composition according to claim 9, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

11. The composition according to claim 10, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

12. The composition according to claim 9, wherein said condensation aerosol particles are characterized by less than 2.5% amantadine degradation products.

13. A composition for delivery of deprenyl consisting of a condensation aerosol

a) formed by volatilizing a thin layer of deprenyl on a solid support, having the surface texture of a metal foil, to a temperature sufficient to produce a heated vapor of deprenyl and condensing the heated vapor of deprenyl to form condensation aerosol particles,

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

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

14. The composition according to claim 13, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

15. The composition according to claim 14, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

16. The composition according to claim 13, wherein said condensation aerosol particles are characterized by less than 2.5% deprenyl degradation products.

17. A composition for delivery of ropinerole consisting of a condensation aerosol

a) formed by volatilizing a thin layer of ropinerole on a solid support, having the surface texture of a metal foil, to a temperature sufficient to produce a heated vapor of ropinerole and condensing the heated vapor of ropinerole to form condensation aerosol particles,

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

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

18. The composition according to claim 17, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

19. The composition according to claim 18, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

20. A method of producing benzotropine in an aerosol form comprising:

a. heating a thin layer of benzotropine on a solid support, having the surface texture of a metal foil, to a temperature sufficient to volatilize the benzotropine to form a heated vapor of the benzotropine, and

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

21. The method according to claim 20, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

22. The method according to claim 21, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

23. A method of producing pergolide in an aerosol form comprising:

a. heating a thin layer of pergolide on a solid support, having the surface texture of a metal foil, to a temperature sufficient to volatilize the pergolide to form a heated vapor of the pergolide, and

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

24. The method according to claim 23, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

25. The method according to claim 24, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

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

a. heating a thin layer of amantadine on a solid support, having the surface texture of a metal foil, to a temperature sufficient to volatilize the amantadine to form a heated vapor of the amantadine, and

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

27. The method according to claim 26, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

28. The method according to claim 27, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

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

a. heating a thin layer of deprenyl on a solid support, having the surface texture of a metal foil, to a temperature sufficient to volatilize the deprenyl to form a heated vapor of the deprenyl, and

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

30. The method according to claim 29, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

31. The method according to claim 30, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

32. A method of producing ropinerole in an aerosol form comprising:

a. heating a thin layer of ropinerole on a solid support, having the surface texture of a metal foil, to a temperature sufficient to volatilize the ropinerole to form a heated vapor of the ropinerole, and

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

33. The method according to claim 32, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

34. The method according to claim 33, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.