Delivery of antihistamines through an inhalation route
View Patent ↗The present invention relates to the delivery of antihistamines through an inhalation route. Specifically, it relates to aerosols containing antihistamines that are used in inhalation therapy. In a method aspect of the present invention, an antihistamine is delivered to a patient through an inhalation route. The method comprises: a) heating a thin layer of an antihistamine, on a solid support, to form a vapor; and, b) passing air through the heated vapor to produce aerosol particles having less than 5% antihistamine drug degradation products. In a kit aspect of the present invention, a kit for delivering an antihistamine through an inhalation route is provided which comprises: a) a thin layer of an antihistamine drug and b) a device for dispensing said thin layer as a condensation aerosol.
1. A condensation aerosol for delivery of a drug selected from the group consisting of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine and promethazine,
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 condensation aerosol according to claim 1 , wherein the condensation aerosol is formed at a rate greater than 10 9 particles per second.
3. The condensation aerosol according to claim 2 , wherein the condensation aerosol is formed at a rate greater than 10 10 particles per second.
4. A method of producing a drug selected from the group consisting of azatadine, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, loratadine, pyrilamine, hydroxyzine and promethazine in an aerosol form comprising:
a. heating a thin layer containing the drug, on a solid support, to produce a vapor of the drug, and
b. providing an air flow through 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.
5. The method according to claim 4 , wherein the condensation aerosol is formed at a rate greater than 10 9 particles per second.
6. The method according to claim 5 , wherein the condensation aerosol is formed at a rate greater than 10 10 particles per second.
7. The condensation aerosol according to claim 1 , wherein the condensation aerosol is characterized by an MMAD of 0.1 to 5 microns.
8. The condensation aerosol according to claim 1 , wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.
9. The condensation aerosol according to claim 1 , wherein the condensation aerosol is characterized by an MMAD of about 0.2 to about 3 microns.
10. The condensation aerosol according to claim 1 , wherein the condensation aerosol is characterized by less than 5% drug degradation products by weight.
11. The condensation aerosol according to claim 10 , wherein the condensation aerosol is characterized by less than 2.5% drug degradation products by weight.
12. The condensation aerosol according to claim 1 , wherein the solid support is a metal foil.
13. The condensation aerosol according to claim 1 , wherein the drug is azatadine.
14. The condensation aerosol according to claim 1 , wherein the drug is brompheniramine.
15. The condensation aerosol according to claim 1 , wherein the drug is carbinoxamine.
16. The condensation aerosol according to claim 1 , wherein the drug is chlorpheniramine.
17. The condensation aerosol according to claim 1 , wherein the drug is clemastine.
18. The condensation aerosol according to claim 1 , wherein the drug is cyproheptadine.
19. The condensation aerosol according to claim 1 , wherein the drug is loratadine.
20. The condensation aerosol according to claim 1 , wherein the drug is pyrilamine.
21. The condensation aerosol according to claim 1 , wherein the drug is hydroxyzine.
22. The condensation aerosol according to claim 1 , wherein the drug is promethazine.
23. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of 0.1 to 5 microns.
24. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.
25. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of about 0.2 to about 3 microns.
26. The method according to claim 4 , wherein the condensation aerosol is characterized by less than 5% drug degradation products by weight.
27. The method according to claim 26 , wherein the condensation aerosol is characterized by less than 2.5% drug degradation products by weight.
28. The method according to claim 4 , wherein the solid support is a metal foil.
29. The method according to claim 4 , wherein the drug is azatadine.
30. The method according to claim 4 , wherein the drug is brompheniramine.
31. The method according to claim 4 , wherein the drug is carbinoxamine.
32. The method according to claim 4 , wherein the drug is chlorpheniramine.
33. The method according to claim 4 , wherein the drug is clemastine.
34. The method according to claim 4 , wherein the drug is cyproheptadine.
35. The method according to claim 4 , wherein the drug is loratadine.
36. The method according to claim 4 , wherein the drug is pyrilamine.
37. The method according to claim 4 , wherein the drug is hydroxyzine.
38. The method according to claim 4 , wherein the drug is promethazine.
39. A condensation aerosol for delivery of azatadine, wherein the condensation aerosol is formed by heating a thin layer containing azatadine, on a solid support, to produce a vapor of azatadine, and condensing the vapor to form a condensation aerosol characterized by less than 5% azatadine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
40. A condensation aerosol for delivery of brompheniramine, wherein the condensation aerosol is formed by heating a thin layer containing brompheniramine, on a solid support, to produce a vapor of brompheniramine, and condensing the vapor to form a condensation aerosol characterized by less than 5% brompheniramine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
41. A condensation aerosol for delivery of carbinoxamine, wherein the condensation aerosol is formed by heating a thin layer containing carbinoxamine, on a solid support, to produce a vapor of carbinoxamine, and condensing the vapor to form a condensation aerosol characterized by less than 5% carbinoxamine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
42. A condensation aerosol for delivery of chlorpheniramine, wherein the condensation aerosol is formed by heating a thin layer containing chlorpheniramine, on a solid support, to produce a vapor of chlorpheniramine, and condensing the vapor to form a condensation aerosol characterized by less than 5% chlorpheniramine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
43. A condensation aerosol for delivery of clemastine, wherein the condensation aerosol is formed by heating a thin layer containing clemastine, on a solid support, to produce a vapor of clemastine, and condensing the vapor to form a condensation aerosol characterized by less than 5% clemastine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
44. A condensation aerosol for delivery of cyproheptadine, wherein the condensation aerosol is formed by heating a thin layer containing cyproheptadine, on a solid support, to produce a vapor of cyproheptadine, and condensing the vapor to form a condensation aerosol characterized by less than 5% cyproheptadine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
45. A condensation aerosol for delivery of loratadine, wherein the condensation aerosol is formed by heating a thin layer containing loratadine, on a solid support, to produce a vapor of loratadine, and condensing the vapor to form a condensation aerosol characterized by less than 5% loratadine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
46. A condensation aerosol for delivery of pyrilamine, wherein the condensation aerosol is formed by heating a thin layer containing pyrilamine, on a solid support, to produce a vapor of pyrilamine, and condensing the vapor to form a condensation aerosol characterized by less than 5% pyrilamine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
47. A condensation aerosol for delivery of hydroxyzine, wherein the condensation aerosol is formed by heating a thin layer containing hydroxyzine, on a solid support, to produce a vapor of hydroxyzine, and condensing the vapor to form a condensation aerosol characterized by less than 5% hydroxyzine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
48. A condensation aerosol for delivery of promethazine, wherein the condensation aerosol is formed by heating a thin layer containing promethazine, on a solid support, to produce a vapor of promethazine, and condensing the vapor to form a condensation aerosol characterized by less than 5% promethazine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
49. A method of producing azatadine in an aerosol form comprising:
a. heating a thin layer containing azatadine, on a solid support, to produce a vapor of azatadine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% azatadine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
50. A method of producing brompheniramine in an aerosol form comprising:
a. heating a thin layer containing brompheniramine, on a solid support, to produce a vapor of brompheniramine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% brompheniramine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
51. A method of producing carbinoxamine in an aerosol form comprising:
a. heating a thin layer containing carbinoxamine, on a solid support, to produce a vapor of carbinoxamine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% carbinoxamine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
52. A method of producing chlorpheniramine in an aerosol form comprising:
a. heating a thin layer containing chlorpheniramine, on a solid support, to produce a vapor of chlorpheniramine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% chlorpheniramine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
53. A method of producing clemastine in an aerosol form comprising:
a. heating a thin layer containing clemastine, on a solid support, to produce a vapor of clemastine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% clemastine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
54. A method of producing cyproheptadine in an aerosol form comprising:
a. heating a thin layer containing cyproheptadine, on a solid support, to produce a vapor of cyproheptadine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% cyproheptadine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
55. A method of producing loratadine in an aerosol form comprising:
a. heating a thin layer containing loratadine, on a solid support, to produce a vapor of loratadine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% loratadine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
56. A method of producing pyrilamine in an aerosol form comprising:
a. heating a thin layer containing pyrilamine, on a solid support, to produce a vapor of pyrilamine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% pyrilamine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
57. A method of producing hydroxyzine in an aerosol form comprising:
a. heating a thin layer containing hydroxyzine, on a solid support, to produce a vapor of hydroxyzine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% hydroxyzine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
58. A method of producing promethazine in an aerosol form comprising:
a. heating a thin layer containing promethazine, on a solid support, to produce a vapor of promethazine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% promethazine degradation products by weight, and an MMAD of about 0.2 to 3 microns.