Delivery of antipsychotics through an inhalation route
View Patent ↗The present invention relates to the delivery of antipsychotics through an inhalation route. Specifically, it relates to aerosols containing antipsychotics that are used in inhalation therapy. In a method aspect of the present invention, an antipsychotic is delivered to a patient through an inhalation route. The method comprises: a) heating a thin layer of an antipsychotic, on a solid support, to form a vapor; and, b) passing air through the heated vapor to produce aerosol particles having less than 5% antipsychotic drug degradation products. In a kit aspect of the present invention, a kit for delivering an antipsychotic through an inhalation route is provided which comprises: a) a thin film of an antipsychotic and b) a device for dispensing said thin film as a condensation aerosol.
1. A condensation aerosol for delivery of a drug selected from the group consisting of olanzapine, trifluoperazine, haloperidol, loxapine, risperidone, clozapine, quetiapine, promazine, thiothixene, chlorpromazine, droperidol, prochlorperazine and fluphenazine,
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 olanzapine, trifluoperazine, haloperidol, loxapine, risperidone, clozapine, quetiapine, promazine, thiothixene, chlorpromazine, droperidol, prochlorperazine and fluphenazine, 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 olanzapine.
14. The condensation aerosol according to claim 1 , wherein the drug is trifluoperazine.
15. The condensation aerosol according to claim 1 , wherein the drug is haloperidol.
16. The condensation aerosol according to claim 1 , wherein the drug is loxapine.
17. The condensation aerosol according to claim 1 , wherein the drug is risperidone.
18. The condensation aerosol according to claim 1 , wherein the drug is clozapine.
19. The condensation aerosol according to claim 1 , wherein the drug is quetiapine.
20. The condensation aerosol according to claim 1 , wherein the drug is promazine.
21. The condensation aerosol according to claim 1 , wherein the drug is thiothixene.
22. The condensation aerosol according to claim 1 , wherein the drug is chlorpromazine.
23. The condensation aerosol according to claim 1 , wherein the drug is droperidol.
24. The condensation aerosol according to claim 1 , wherein the drug is prochlorperazine.
25. The condensation aerosol according to claim 1 , wherein the drug is fluphenazine.
26. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of 0.1 to 5 microns.
27. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of less than 3 microns.
28. The method according to claim 4 , wherein the condensation aerosol is characterized by an MMAD of about 0.2 to 3 microns.
29. The method according to claim 4 , wherein the condensation aerosol is characterized by less than 5% drug degradation products by weight.
30. The method according to claim 29 , wherein the condensation aerosol is characterized by less than 2.5% drug degradation products by weight.
31. The method according to claim 4 , wherein the solid support is a metal foil.
32. The method according to claim 4 , wherein the drug is olanzapine.
33. The method according to claim 4 , wherein the drug is trifluoperazine.
34. The method according to claim 4 , wherein the drug is haloperidol.
35. The method according to claim 4 , wherein the drug is loxapine.
36. The method according to claim 4 , wherein the drug is risperidone.
37. The method according to claim 4 , wherein the drug is clozapine.
38. The method according to claim 4 , wherein the drug is quetiapine.
39. The method according to claim 4 , wherein the drug is promazine.
40. The method according to claim 4 , wherein the drug is thiothixene.
41. The method according to claim 4 , wherein the drug is chlorpromazine.
42. The method according to claim 4 , wherein the drug is droperidol.
43. The method according to claim 4 , wherein the drug is prochlorperazine.
44. The method according to claim 4 , wherein the drug is fluphenazine.
45. A condensation aerosol for delivery of olanzapine, wherein the condensation aerosol is formed by heating a thin layer containing olanzapine, on a solid support, to produce a vapor of olanzapine, and condensing the vapor to form a condensation aerosol characterized by less than 5% olanzapine degradation products by weight, and an MMAD of 0.2 to 3 microns.
46. A condensation aerosol for delivery of trifluoperazine, wherein the condensation aerosol is formed by heating a thin layer containing trifluoperazine, on a solid support, to produce a vapor of trifluoperazine, and condensing the vapor to form a condensation aerosol characterized by less than 5% trifluoperazine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
47. A condensation aerosol for delivery of haloperidol, wherein the condensation aerosol is formed by heating a thin layer containing haloperidol, on a solid support, to produce a vapor of haloperidol, and condensing the vapor to form a condensation aerosol characterized by less than 5% haloperidol degradation products by weight, and an MMAD of about 0.2 to 3 microns.
48. A condensation aerosol for delivery of loxapine, wherein the condensation aerosol is formed by heating a thin layer containing loxapine, on a solid support, to produce a vapor of loxapine, and condensing the vapor to form a condensation aerosol characterized by less than 5% loxapine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
49. A condensation aerosol for delivery of risperidone, wherein the condensation aerosol is formed by heating a thin layer containing risperidone, on a solid support, to produce a vapor of risperidone, and condensing the vapor to form a condensation aerosol characterized by less than 5% risperidone degradation products by weight, and an MMAD of about 0.2 to 3 microns.
50. A condensation aerosol for delivery of clozapine, wherein the condensation aerosol is formed by heating a thin layer containing clozapine, on a solid support, to produce a vapor of clozapine, and condensing the vapor to form a condensation aerosol characterized by less than 5% clozapine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
51. A condensation aerosol for delivery of quetiapine, wherein the condensation aerosol is formed by heating a thin layer containing quetiapine, on a solid support, to produce a vapor of quetiapine, and condensing the vapor to form a condensation aerosol characterized by less than 5% quetiapine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
52. A condensation aerosol for delivery of promazine, wherein the condensation aerosol is formed by heating a thin layer containing promazine, on a solid support, to produce a vapor of promazine, and condensing the vapor to form a condensation aerosol characterized by less than 5% promazine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
53. A condensation aerosol for delivery of thiothixene, wherein the condensation aerosol is formed by heating a thin layer containing thiothixene, on a solid support, to produce a vapor of thiothixene, and condensing the vapor to form a condensation aerosol characterized by less than 5% thiothixene degradation products by weight, and an MMAD of about 0.2 to 3 microns.
54. A condensation aerosol for delivery of chlorpromazine, wherein the condensation aerosol is formed by heating a thin layer containing chlorpromazine, on a solid support, to produce a vapor of chlorpromazine, and condensing the vapor to form a condensation aerosol characterized by less than 5% chlorpromazine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
55. A condensation aerosol for delivery of droperidol, wherein the condensation aerosol is formed by heating a thin layer containing droperidol, on a solid support, to produce a vapor of droperidol, and condensing the vapor to form a condensation aerosol characterized by less than 5% droperidol degradation products by weight, and an MMAD of about 0.2 to 3 microns.
56. A condensation aerosol for delivery of prochlorperazine, wherein the condensation aerosol is formed by heating a thin layer containing prochlorperazine, on a solid support, to produce a vapor of prochlorperazine, and condensing the vapor to form a condensation aerosol characterized by less than 5% prochlorperazine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
57. A condensation aerosol for delivery of fluphenazine, wherein the condensation aerosol is formed by heating a thin layer containing fluphenazine, on a solid support, to produce a vapor of fluphenazine, and condensing the vapor to form a condensation aerosol characterized by less than 5% fluphenazine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
58. A method of producing olanzapine in an aerosol form comprising:
a. heating a thin layer containing olanzapine, on a solid support, to produce a vapor of olanzapine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% olanzapine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
59. A method of producing trifluoperazine in an aerosol form comprising:
a. heating a thin layer containing trifluoperazine, on a solid support, to produce a vapor of trifluoperazine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% trifluoperazine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
60. A method of producing haloperidol in an aerosol form comprising:
a. heating a thin layer containing haloperidol, on a solid support, to produce a vapor of haloperidol, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% haloperidol degradation products by weight, and an MMAD of about 0.2 to 3 microns.
61. A method of producing loxapine in an aerosol form comprising:
a. heating a thin layer containing loxapine, on a solid support, to produce a vapor of loxapine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% loxapine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
62. A method of producing risperidone in an aerosol form comprising:
a. heating a thin layer containing risperidone, on a solid support, to produce a vapor of risperidone, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% risperidone degradation products by weight, and an MMAD of about 0.2 to 3 microns.
63. A method of producing clozapine in an aerosol form comprising:
a. heating a thin layer containing clozapine, on a solid support, to produce a vapor of clozapine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% clozapine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
64. A method of producing quetiapine in an aerosol form comprising:
a. heating a thin layer containing quetiapine, on a solid support, to produce a vapor of quetiapine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% quetiapine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
65. A method of producing promazine in an aerosol form comprising:
a. heating a thin layer containing promazine, on a solid support, to produce a vapor of promazine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% promazine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
66. A method of producing thiothixene in an aerosol form comprising:
a. heating a thin layer containing thiothixene, on a solid support, to produce a vapor of thiothixene, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% thiothixene degradation products by weight, and an MMAD of about 0.2 to 3 microns.
67. A method of producing chlorpromazine in an aerosol form comprising:
a. heating a thin layer containing chlorpromazine, on a solid support, to produce a vapor of chlorpromazine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% chlorpromazine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
68. A method of producing droperidol in an aerosol form comprising:
a. heating a thin layer containing droperidol, on a solid support, to produce a vapor of droperidol, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% droperidol degradation products by weight, and an MMAD of about 0.2 to 3 microns.
69. A method of producing prochlorperazine in an aerosol form comprising:
a. heating a thin layer containing prochlorperazine, on a solid support, to produce a vapor of prochlorperazine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% prochlorperazine degradation products by weight, and an MMAD of about 0.2 to 3 microns.
70. A method of producing fluphenazine in an aerosol form comprising:
a. heating a thin layer containing fluphenazine, on a solid support, to produce a vapor of fluphenazine, and
b. providing an air flow through the vapor to form a condensation aerosol characterized by less than 5% fluphenazine degradation products by weight, and an MMAD of about 0.2 to 3 microns.