Delivery of antidepressants through an inhalation route

• US 7,060,254 B2
• Filed: 01/27/2004
• Issued: 06/13/2006
• 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): Padmanabhan, Sreeni
• Assistant Examiner(s): Haghighatian, Mina
• Application Number:
  US10/766,566
• Publication Number:
  US 20040191179A1
• Time in Patent Office: 868 Days
• Field of Search: 424/45, 424/46, 424/489, 424/499, 424/43, 424/434, 424/789, 128/200.14, 128/200.24, 128/203.15, 128/200.12, 514/165, 514/958
• 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 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 condensation aerosol for delivery of a drug selected from the group consisting of bupropion, nefazodone, perphenazine, trazodone, trimipramine, venlafaxine, tranylcypromine, citalopram, fluoxetine, fluvoxamine, mirtazepine, paroxetine, sertraline, amoxipine, clomipramine, doxepin, imipramine, maprotiline, nortryptiline, valproic acid and protryptyline, 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 10⁹ particles per second.

3. The condensation aerosol according to claim 2, wherein the condensation aerosol is formed at a rate greater than 10¹⁰ particles per second.

7. The condensation aerosol according to claim 1, wherein the condensation aerosol is characterized by an MMAD of 0.2 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 bupropion.

14. The condensation aerosol according to claim 1, wherein the drug is nefazodone.

15. The condensation aerosol according to claim 1, wherein the drug is perphenazine.

16. The condensation aerosol according to claim 1, wherein the drug is trazodone.

17. The condensation aerosol according to claim 1, wherein the drug is trimipramine.

18. The condensation aerosol according to claim 1, wherein the drug is venlafaxine.

19. The condensation aerosol according to claim 1, wherein the drug is tranylcypromine.

20. The condensation aerosol according to claim 1, wherein the drug is citalopram.

21. The condensation aerosol according to claim 1, wherein the drug is fluoxetine.

22. The condensation aerosol according to claim 1, wherein the drug is fluvoxamine.

23. The condensation aerosol according to claim 1, wherein the drug is mirtazepine.

24. The condensation aerosol according to claim 1, wherein the drug is paroxetine.

25. The condensation aerosol according to claim 1, wherein the drug is sertraline.

26. The condensation aerosol according to claim 1, wherein the drug is amoxipine.

27. The condensation aerosol according to claim 1, wherein the drug is clomipramine.

28. The condensation aerosol according to claim 1, wherein the drug is doxepin.

29. The condensation aerosol according to claim 1, wherein the drug is imipramine.

30. The condensation aerosol according to claim 1, wherein the drug is maprotiline.

31. The condensation aerosol according to claim 1, wherein the drug is nortryptiline.

32. The condensation aerosol according to claim 1, wherein the drug is valproic acid.

33. The condensation aerosol according to claim 1, wherein the drug is protryptyline.

4. A method of producing a drug selected from the group consisting of bupropion, nefazodone, perphenazine, trazodone, trimipramine, venlafaxine, tranylcypromine, citalopram, fluoxetine, fluvoxamine, mirtazepine, paroxetine, sertraline, amoxipine, clomipramine, doxepin, imipramine, maprotiline, nortryptiline, valproic acid and protryptyline 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 10⁹ particles per second.

6. The method according to claim 5, wherein the condensation aerosol is formed at a rate greater than 10¹⁰ particles per second.

34. The method according to claim 4, wherein the condensation aerosol is characterized by an MMAD of 0.2 to 5 microns.

35. The method according to claim 4, wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.

36. The method according to claim 4, wherein the condensation aerosol is characterized by an MMAD of about 0.2 to about 3 microns.

37. The method according to claim 4, wherein the condensation aerosol is characterized by less than 5% drug degradation products by weight.

38. The method according to claim 37, wherein the condensation aerosol is characterized by less than 2.5% drug degradation products by weight.

39. The method according to claim 4, wherein the solid support is a metal foil.

40. The method according to claim 4, wherein the drug is bupropion.

41. The method according to claim 4, wherein the drug is nefazodone.

42. The method according to claim 4, wherein the drug is perphenazine.

43. The method according to claim 4, wherein the drug is trazodone.

44. The method according to claim 4, wherein the drug is trimipramine.

45. The method according to claim 4, wherein the drug is venlafaxine.

46. The method according to claim 4, wherein the drug is tranylcypromine.

47. The method according to claim 4, wherein the drug is citalopram.

48. The method according to claim 4, wherein the drug is fluoxetine.

49. The method according to claim 4, wherein the drug is fluvoxamine.

50. The method according to claim 4, wherein the drug is mirtazepine.

51. The method according to claim 4, wherein the drug is paroxetine.

52. The method according to claim 4, wherein the drug is sertraline.

53. The method according to claim 4, wherein the drug is amoxipine.

54. The method according to claim 4, wherein the drug is clomipramine.

55. The method according to claim 4, wherein the drug is doxepin.

56. The method according to claim 4, wherein the drug is imipramine.

57. The method according to claim 4, wherein the drug is maprotiline.

58. The method according to claim 4, wherein the drug is nortryptiline.

59. The method according to claim 4, wherein the drug is valproic acid.

60. The method according to claim 4, wherein the drug is protryptyline.

61. A condensation aerosol for delivery of bupropion, wherein the condensation aerosol is formed by heating a thin layer containing bupropion, on a solid support, to produce a vapor of bupropion, and condensing the vapor to form a condensation aerosol characterized by less than 5% bupropion degradation products by weight, and an MMAD of about 0.2 to 3 microns.

62. A condensation aerosol for delivery of nefazodone, wherein the condensation aerosol is formed by heating a thin layer containing nefazodone, on a solid support, to produce a vapor of nefazodone, and condensing the vapor to form a condensation aerosol characterized by less than 5% nefazodone degradation products by weight, and an MMAD of about 0.2 to 3 microns.

63. A condensation aerosol for delivery of perphenazine, wherein the condensation aerosol is formed by heating a thin layer containing perphenazine, on a solid support, to produce a vapor of perphenazine, and condensing the vapor to form a condensation aerosol characterized by less than 5% perphenazine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

64. A condensation aerosol for delivery of trazodone, wherein the condensation aerosol is formed by heating a thin layer containing trazodone, on a solid support, to produce a vapor of trazodone, and condensing the vapor to form a condensation aerosol characterized by less than 5% trazodone degradation products by weight, and an MMAD of about 0.2 to 3 microns.

65. A condensation aerosol for delivery of trimipramine, wherein the condensation aerosol is formed by heating a thin layer containing trimipramine, on a solid support, to produce a vapor of trimipramine, and condensing the vapor to form a condensation aerosol characterized by less than 5% trimipramine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

66. A condensation aerosol for delivery of venlafaxine, wherein the condensation aerosol is formed by heating a thin layer containing venlafaxine, on a solid support, to produce a vapor of venlafaxine, and condensing the vapor to form a condensation aerosol characterized by less than 5% venlafaxine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

67. A condensation aerosol for delivery of tranylcypromine, wherein the condensation aerosol is formed by heating a thin layer containing tranylcypromine, on a solid support, to produce a vapor of tranylcypromine, and condensing the vapor to form a condensation aerosol characterized by less than 5% tranylcypromine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

68. A condensation aerosol for delivery of citalopram, wherein the condensation aerosol is formed by heating a thin layer containing citalopram, on a solid support, to produce a vapor of citalopram, and condensing the vapor to form a condensation aerosol characterized by less than 5% citalopram degradation products by weight, and an MMAD of about 0.2 to 3 microns.

69. A condensation aerosol for delivery of fluoxetine, wherein the condensation aerosol is formed by heating a thin layer containing fluoxetine, on a solid support, to produce a vapor of fluoxetine, and condensing the vapor to form a condensation aerosol characterized by less than 5% fluoxetine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

70. A condensation aerosol for delivery of fluvoxamine, wherein the condensation aerosol is formed by heating a thin layer containing fluvoxamine, on a solid support, to produce a vapor of fluvoxamine, and condensing the vapor to form a condensation aerosol characterized by less than 5% fluvoxamine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

71. A condensation aerosol for delivery of mirtazepine, wherein the condensation aerosol is formed by heating a thin layer containing mirtazepine, on a solid support, to produce a vapor of mirtazepine, and condensing the vapor to form a condensation aerosol characterized by less than 5% mirtazepine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

72. A condensation aerosol for delivery of paroxetine, wherein the condensation aerosol is formed by heating a thin layer containing paroxetine, on a solid support, to produce a vapor of paroxetine, and condensing the vapor to form a condensation aerosol characterized by less than 5% paroxetine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

73. A condensation aerosol for delivery of sertraline, wherein the condensation aerosol is formed by heating a thin layer containing sertraline, on a solid support, to produce a vapor of sertraline, and condensing the vapor to form a condensation aerosol characterized by less than 5% sertraline degradation products by weight, and an MMAD of about 0.2 to 3 microns.

74. A condensation aerosol for delivery of amoxipine, wherein the condensation aerosol is formed by heating a thin layer containing amoxipine, on a solid support, to produce a vapor of amoxipine, and condensing the vapor to form a condensation aerosol characterized by less than 5% amoxipine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

75. A condensation aerosol for delivery of clomipramine, wherein the condensation aerosol is formed by heating a thin layer containing clomipramine, on a solid support, to produce a vapor of clomipramine, and condensing the vapor to form a condensation aerosol characterized by less than 5% clomipramine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

76. A condensation aerosol for delivery of doxepin, wherein the condensation aerosol is formed by heating a thin layer containing doxepin, on a solid support, to produce a vapor of doxepin, and condensing the vapor to form a condensation aerosol characterized by less than 5% doxepin degradation products by weight, and an MMAD of about 0.2 to 3 microns.

77. A condensation aerosol for delivery of imipramine, wherein the condensation aerosol is formed by heating a thin layer containing imipramine, on a solid support, to produce a vapor of imipramine, and condensing the vapor to form a condensation aerosol characterized by less than 5% imipramine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

78. A condensation aerosol for delivery of maprotiline, wherein the condensation aerosol is formed by heating a thin layer containing maprotiline, on a solid support, to produce a vapor of maprotiline, and condensing the vapor to form a condensation aerosol characterized by less than 5% maprotiline degradation products by weight, and an MMAD of about 0.2 to 3 microns.

79. A condensation aerosol for delivery of nortryptiline, wherein the condensation aerosol is formed by heating a thin layer containing nortryptiline, on a solid support, to produce a vapor of nortryptiline, and condensing the vapor to form a condensation aerosol characterized by less than 5% nortryptiline degradation products by weight, and an MMAD of about 0.2 to 3 microns.

80. A condensation aerosol for delivery of vaiproic acid, wherein the condensation aerosol is formed by heating a thin layer containing valproic acid, on a solid support, to produce a vapor of valproic acid, and condensing the vapor to form a condensation aerosol characterized by less than 5% valproic acid degradation products by weight, and an MMAD of about 0.2 to 3 microns.

81. A condensation aerosol for delivery of protryptyline, wherein the condensation aerosol is formed by heating a thin layer containing protryptyline, on a solid support, to produce a vapor of protryptyline, and condensing the vapor to form a condensation aerosol characterized by less than 5% protryptyline degradation products by weight, and an MMAD of about 0.2 to 3 microns.

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

a. heating a thin layer containing bupropion, on a solid support, to produce a vapor of bupropion, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% bupropion degradation products by weight, and an MMAD of about 0.2 to 3 microns.

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

a. heating a thin layer containing nefazodone, on a solid support, to produce a vapor of nefazodone, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% nefazodone degradation products by weight, and an MMAD of about 0.2 to 3 microns.

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

a. heating a thin layer containing perphenazine, on a solid support, to produce a vapor of perphenazine, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% perphenazine degradation products by weight, and an MMAD of 0.2 to 3 microns.

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

a. heating a thin layer containing trazodone, on a solid support, to produce a vapor of trazodone, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% trazodone degradation products by weight, and an MMAD of about 0.2 to 3 microns.

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

a. heating a thin layer containing trimipramine, on a solid support, to produce a vapor of trimipramine, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% trimipramine degradation products by weight, and an MMAD of 0.2 to 3 microns.

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

a. heating a thin layer containing venlafaxine, on a solid support, to produce a vapor of venlafaxine, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% venlafaxine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

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

a. heating a thin layer containing tranylcypromine, on a solid support, to produce a vapor of tranylcypromine, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% tranylcypromine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

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

a. heating a thin layer containing citalopram, on a solid support, to produce a vapor of citalopram, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% citalopram degradation products by weight, and an MMAD of about 0.2 to 3 microns.

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

a. heating a thin layer containing fluoxetine, on a solid support, to produce a vapor of fluoxetine, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% fluoxetine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

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

a. heating a thin layer containing fluvoxamine, on a solid support, to produce a vapor of fluvoxamine, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% fluvoxamine degradation products by weight, and an MMAD of 0.2 to 3 microns.

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

a. heating a thin layer containing mirtazepine, on a solid support, to produce a vapor of mirtazepine, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% mirtazepine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

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

a. heating a thin layer containing paroxetine, on a solid support, to produce a vapor of paroxetine, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% paroxetine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

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

a. heating a thin layer containing sertraline, on a solid support, to produce a vapor of sertraline, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% sertraline degradation products by weight, and an MMAD of about 0.2 to 3 microns.

95. A method of producing amoxipine in an aerosol form comprising:

a. heating a thin layer containing amoxipine, on a solid support, to produce a vapor of amoxipine, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% amoxipine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

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

a. heating a thin layer containing clomipramine, on a solid support, to produce a vapor of clomipramine, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% clomipramine degradation products by weight, and an MMAD of 0.2 to 3 microns.

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

a. heating a thin layer containing doxepin, on a solid support, to produce a vapor of doxepin, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% doxepin degradation products by weight, and an MMAD of about 0.2 to 3 microns.

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

a. heating a thin layer containing imipramine, on a solid support, to produce a vapor of imipramine, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% imipramine degradation products by weight, and an MMAD of about 0.2 to 3 microns.

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

a. heating a thin layer containing maprotiline, on a solid support, to produce a vapor of maprotiline, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% maprotiline degradation products by weight, and an MMAD of about 0.2 to 3 microns.

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

a. heating a thin layer containing nortryptiline, on a solid support, to produce a vapor of nortryptiline, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% nortryptiline degradation products by weight, and an MMAD of 0.2 to 3 microns.

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

a. heating a thin layer containing valproic acid, on a solid support, to produce a vapor of vaiproic acid, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% valproic acid degradation products by weight, and an MMAD of 0.2 to 3 microns.

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

a. heating a thin layer containing protryptyline, on a solid support, to produce a vapor of protryptyline, and

b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% protryptyline degradation products by weight, and an MMAD of 0.2 to 3 microns.