Delivery of antidepressants through an inhalation route

• US 20040191179A1
• Filed: 01/27/2004
• Published: 09/30/2004
• 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 7,060,254 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 antidepressants through an inhalation route. Specifically, it relates to aerosols containing an antidepressant that are used in inhalation therapy. In a method aspect of the present invention, an antidepressant is administered to a patient through an inhalation route. The method comprises: a) heating a thin layer of an antidepressant, on a solid support, form a vapor; and, b) passing air through the heated vapor to produce aerosol particles having less than 5% antidepressant degradation products. In a kit aspect of the present invention, a kit for delivering an antidepressant through an inhalation route to a mammal is provided which comprises: a) a thin coating of an antidepressant composition and b) a device for dispensing said thin coating as a condensation aerosol.

Claims

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

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

b. wherein said condensation aerosol particles are characterized by less than 5% bupropion 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. A composition for delivery of nefazodone consisting of a condensation aerosol

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

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

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

5. The composition according to claim 4, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

6. The composition according to claim 5, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

7. A composition for delivery of perphenazine consisting of a condensation aerosol

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

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

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

8. The composition according to claim 7, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

9. The composition according to claim 8, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

10. A composition for delivery of trazodone consisting of a condensation aerosol

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

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

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

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

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

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

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

b. wherein said condensation aerosol particles are characterized by less than 5% trimipramine 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. A composition for delivery of venlafaxine consisting of a condensation aerosol

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

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

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

17. The composition according to claim 16, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

18. The composition according to claim 17, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

19. A composition for delivery of tranylcypromine consisting of a condensation aerosol

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

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

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

20. The composition according to claim 19, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

21. The composition according to claim 20, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

22. A composition for delivery of citalopram consisting of a condensation aerosol

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

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

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

23. The composition according to claim 22, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

24. The composition according to claim 23, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

25. A composition for delivery of fluoxetine consisting of a condensation aerosol

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

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

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

26. The composition according to claim 25, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

27. The composition according to claim 26, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

28. A composition for delivery of fluvoxamine consisting of a condensation aerosol

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

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

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

29. The composition according to claim 28, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

30. The composition according to claim 29, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

31. A composition for delivery of mirtazepine consisting of a condensation aerosol

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

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

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

32. The composition according to claim 31, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

33. The composition according to claim 32 wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

34. A composition for delivery of paroxetine consisting of a condensation aerosol

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

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

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

35. The composition according to claim 34, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

36. The composition according to claim 35, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

37. A composition for delivery of sertraline consisting of a condensation aerosol

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

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

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

38. The composition according to claim 37, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

39. The composition according to claim 38, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

40. A composition for delivery of amoxipine consisting of a condensation aerosol

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

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

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

41. The composition according to claim 40, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

42. The composition according to claim 41, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

43. A composition for delivery of clomipramine consisting of a condensation aerosol

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

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

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

44. The composition according to claim 43, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

45. The composition according to claim 44, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

46. A composition for delivery of doxepin consisting of a condensation aerosol

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

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

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

47. The composition according to claim 46, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

48. The composition according to claim 47, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

49. A composition for delivery of imipramine consisting of a condensation aerosol

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

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

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

50. The composition according to claim 49, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

51. The composition according to claim 50, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

52. A composition for delivery of maprotiline consisting of a condensation aerosol

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

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

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

53. The composition according to claim 52, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

54. The composition according to claim 53, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

55. A composition for delivery of nortryptiline consisting of a condensation aerosol

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

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

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

56. The composition according to claim 55, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

57. The composition according to claim 56, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

58. A composition for delivery of valproic acid consisting of a condensation aerosol

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

b. wherein said condensation aerosol particles are characterized by less than 5% valproic acid degradation products, and

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

59. The composition according to claim 58, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

60. The composition according to claim 59, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

61. A composition for delivery of protryptyline consisting of a condensation aerosol

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

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

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

62. The composition according to claim 61, wherein the aerosol particles are formed at a rate of at least 10⁹ particles per second.

63. The composition according to claim 62, wherein the aerosol particles are formed at a rate of at least 10¹⁰ particles per second.

64. A method of producing bupropion in an aerosol form comprising:

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

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

65. The method according to claim 64, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

66. The method according to claim 65, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

67. A method of producing nefazodone in an aerosol form comprising:

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

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

68. The method according to claim 67, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

69. The method according to claim 68, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

70. A method of producing perphenazine in an aerosol form comprising:

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

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

71. The method according to claim 70, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

72. The method according to claim 71, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

73. A method of producing trazodone in an aerosol form comprising:

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

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

74. The method according to claim 73, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

75. The method according to claim 74, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

76. A method of producing trimipramine in an aerosol form comprising:

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

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

77. The method according to claim 76, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

78. The method according to claim 77, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

79. A method of producing venlafaxine in an aerosol form comprising:

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

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

80. The method according to claim 79, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

81. The method according to claim 80, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

82. A method of producing tranylcypromine in an aerosol form comprising:

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

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

83. The method according to claim 82, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

84. The method according to claim 83, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

85. A method of producing citalopram in an aerosol form comprising:

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

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

86. The method according to claim 85, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

87. The method according to claim 86, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

88. A method of producing fluoxetine in an aerosol form comprising:

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

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

89. The method according to claim 88, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

90. The method according to claim 89, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

91. A method of producing fluvoxamine in an aerosol form comprising:

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

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

92. The method according to claim 91, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

93. The method according to claim 92, wherein the aerosol particles are formed at a rate of greater than 10¹⁰particles per second.

94. A method of producing mirtazepine in an aerosol form comprising:

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

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

95. The method according to claim 94, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

96. The method according to claim 95, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

97. A method of producing paroxetine in an aerosol form comprising:

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

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

98. The method according to claim 97, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

99. The method according to claim 98, wherein the aerosol particles are formed at a rate of greater than 10¹⁰particles per second.

100. A method of producing sertraline in an aerosol form comprising:

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

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

101. The method according to claim 100, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

102. The method according to claim 101, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

103. A method of producing amoxapine in an aerosol form comprising:

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

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

104. The method according to claim 103, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

105. The method according to claim 104, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

106. A method of producing clomipramine in an aerosol form comprising:

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

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

107. The method according to claim 106, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

108. The method according to claim 107, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

109. A method of producing doxepin in an aerosol form comprising:

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

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

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

111. The method according to claim 110, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

112. A method of producing imipramine in an aerosol form comprising:

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

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

113. The method according to claim 112, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

114. The method according to claim 113, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

115. A method of producing maprotiline in an aerosol form comprising:

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

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

116. The method according to claim 115, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

117. The method according to claim 116, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

118. A method of producing nortryptiline in an aerosol form comprising:

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

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

119. The method according to claim 118, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

120. The method according to claim 119, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

121. A method of producing valproic acid in an aerosol form comprising:

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

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

122. The method according to claim 121, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

123. The method according to claim 122, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.

124. A method of producing protryptyline in an aerosol form comprising:

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

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

125. The method according to claim 124, wherein the aerosol particles are formed at a rate of greater than 10⁹ particles per second.

126. The method according to claim 125, wherein the aerosol particles are formed at a rate of greater than 10¹⁰ particles per second.