Delivery of erectile dysfunction drugs through an inhalation route

• US 7,115,250 B2
• Filed: 12/30/2003
• Issued: 10/03/2006
• 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: Rabinowitz, Joshua D., Zaffaroni, Alejandro C.
• Primary Examiner(s): Kunz, Gary
• Assistant Examiner(s): Haghighatian, Mina
• Application Number:
  US10/749,535
• Publication Number:
  US 20040156788A1
• Time in Patent Office: 1,008 Days
• Field of Search: 424/45, 424/46, 424/489, 424/499, 514/220, 514/1, 514/958, 128/200.14, 128/200.24, 128/203.15
• 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 erectile dysfunction drugs through an inhalation route. Specifically, it relates to aerosols containing erectile dysfunction drugs that are used in inhalation therapy. In a method aspect of the present invention, an erectile dysfunction drug is delivered to a patient through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises an erectile dysfunction drug, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles with less than 5% erectile dysfunction drug degradation products. In a kit aspect of the present invention, a kit for delivering an erectile dysfunction drug through an inhalation route is provided which comprises: a) a thin coating of an erectile dysfunction drug composition and b) a device for dispensing said thin coating as a condensation aerosol.

Claims

1. A method of treating erectile dysfunction in a patient comprising administering a therapeutic amount of a drug condensation aerosol to the patient by inhalation,

wherein the drug is selected from the group consisting of sildenafil, tadalafil and vardenafil, and

wherein the condensation aerosol is formed by heating a thin layer containing the drug, on a solid support, to produce a vapor of the drug, and condensing the vapor to form a condensation aerosol characterized by less than 10% drug degradation products by weight, and an MMAD of less than 5 microns.

2. The method according to claim 1, wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.

3. The method according to claim 1, wherein peak plasma drug concentration is reached in less than 0.1 hours.

4. The method according to claim 1, wherein the condensation aerosol is formed at a rate greater than 0.5 mg/second.

5. The method according to claim 1, wherein at least 50% by weight of the condensation aerosol is amorphous in form.

6. The method according to claim 1, wherein the therapeutic amount of a drug condensation aerosol comprises between 5 mg and 40 mg of sildenafil delivered in a single inspiration.

7. The method according to claim 1, wherein the therapeutic amount of a drug condensation aerosol comprises between 2.5 mg and 20 mg of tadalafil delivered in a single inspiration.

8. The method according to claim 1, wherein the therapeutic amount of a drug condensation aerosol comprises between 1 mg and 20 mg of vardenafil delivered in a single inspiration.

18. The method according to claim 1, wherein the condensation aerosol is characterized by an MMAD of 0.2 to 5 microns.

19. The method according to claim 2, wherein the condensation aerosol is characterized by an MMAD of 0.2 to 3 microns.

9. A method of administering a drug condensation aerosol to a patient comprising administering the drug condensation aerosol to the patient by inhalation,

wherein the drug is selected from the group consisting of sildenafil, tadalafil and vardenafil, and

wherein the drug condensation aerosol is formed by heating a thin layer containing the drug, on a solid support, to produce a vapor of the drug, and condensing the vapor to form a condensation aerosol characterized by less than 10% drug degradation products by weight, and an MMAD of less than 5 micron.

20. The method according to claim 9, wherein the drug is sildenafil.

21. The method according to claim 9, wherein the drug is tadalafil.

22. The method according to claim 9, wherein the drug is vardenafil.

10. A kit for delivering a drug condensation aerosol comprising:

a. a thin layer containing the drug, on a solid support, wherein the drug is selected from the group consisting of sildenafil, tadalafil and vardenafil, and

b. a device for providing the condensation aerosol, wherein the condensation aerosol is formed by heating the thin layer to produce a vapor of the drug, and condensing the vapor to form a condensation aerosol characterized by less than 10% drug degradation products by weight, and an MMAD of less than 5 microns.

11. The kit according to claim 10, wherein the device comprises:

a. a flow through enclosure containing the solid support,

b. a power source that can be activated to heat the solid support, and

c. at least one portal through which air can be drawn by inhalation,

wherein activation of the power source is effective to produce a vapor of the drug, and drawing air through the enclosure is effective to condense the vapor to form the condensation aerosol.

12. The kit according to claim 11, wherein the heat for heating the solid support is generated by an exothermic chemical reaction.

13. The kit according to claim 12, wherein the exothermic chemical reaction is oxidation of combustible materials.

14. The kit according to claim 11, wherein the heat for heating the solid support is generated by passage of current through an electrical resistance element.

15. The kit according to claim 11, wherein said solid support has a surface area dimensioned to accommodate a therapeutic dose of the drug.

16. The kit according to claim 10, wherein peak plasma drug concentration is reached in less than 0.1 hours.

17. The kit according to claim 10, further including instructions for use.

23. The kit according to claim 10, wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.

24. The kit according to claim 10, wherein the condensation aerosol is characterized by an MMAD of 0.2 to 5 microns.

25. The kit according to claim 23, wherein the condensation aerosol is characterized by an MMAD of 0.2 to 3 microns.

26. The kit according to claim 10, wherein the drug is sildenafil.

27. The kit according to claim 10, wherein the drug is tadalafil.

28. The kit according to claim 10, wherein the drug is vardenafil.

29. The kit according to claim 11, wherein the solid support has a surface to mass ratio of greater than 1 cm² per gram.

30. The kit according to claim 11, wherein the solid support has a surface to volume ratio of greater than 100 per meter.

31. The kit according to claim 11, wherein the solid support is a metal foil.

32. The kit according to claim 31, wherein the metal foil has a thickness of less than 0.25 mm.