Claims
- 1. A composition of matter for the sustained release of fluoxetine to an individual in need of fluoxetine therapy, the composition comprising an amount of a pharmaceutically acceptable salt of fluoxetine in a carrier effective to permit sustained release of fluoxetine at a therapeutically effective rate within the range of 250-3200 μg/hr during an administration period of at least 12 hours in order to administer a therapeutically effective amount of fluoxetine in order to achieve and maintain therapeutic blood or plasma levels throughout a substantial portion of the administration period.
- 2. A composition according to claim 1 wherein the composition is a topical composition and further comprises a permeation enhancing amount of a permeation enhancer.
- 3. A composition according to claim 1 wherein the composition is a topical composition and further comprises an anti-irritant.
- 4. A composition according to claim 3 wherein the salt is fluoxetine acetate or fluoxetine maleate.
- 5. A composition according to claim 3 wherein the anti-irritant comprises a corticosteroid in an amount effective to coadminister said corticosteroid at a rate in excess of 0.1 μg/cm2·hr throughout the administration period in order to reduce skin irritation wherein the total amount of corticosteroid delivered is less than 5 mg/24 hours.
- 6. A composition according to claim 5 wherein the corticosteroid is hydrocortisone.
- 7. A composition according to claim 3 further comprising a permeation enhancer.
- 8. A composition according to claim 7 wherein the permeation enhancer comprises a monoglyceride or mixture of monoglycerides of a fatty acid.
- 9. A composition according to claim 8 further comprising a cosolvent selected from the group consisting of fatty acid esters, lactate esters, and alkyl laurates.
- 10. A composition according to claim 9 wherein the monoglyceride is glycerol monolaurate and the cosolvent is selected from the group consisting of dodecyl acetate, lauryl lactate, and methyl laurate.
- 11. A composition according to claim 7 comprising:
(a) 10 to 50 weight % of a pharmaceutically acceptable salt of fluoxetine; (b) 0.01 to 10 weight % of an anti-irritant; (c) 10 to 50 weight % of a permeation enhancer; and (d) 20 to 80 weight % of a polymeric carrier.
- 12. A composition according to claim 11 comprising 15 to 40 weight % fluoxetine acetate, 0.1 to 10 weight % hydrocortisone, and 10 to 40 weight % of a permeation enhancer comprising glycerol monolaurate and methyl laurate.
- 13. A device for the transdermal administration of fluoxetine at a therapeutically effective rate, comprising:
(a) a reservoir comprising an amount of a pharmaceutically acceptable salt of fluoxetine; (b) a backing behind the body contacting-distal surface of the reservoir; and (c) means for maintaining the reservoir in fluoxetine transmitting relation with a body surface or membrane, said device having a surface area defining an area of fluoxetine delivery of less than about 60 cm2, wherein a therapeutically effective amount of fluoxetine is delivered at a therapeutically effective rate within 250-3200 μg/hr during an administration period of at least 12 hours in order to achieve and maintain therapeutic blood or plasma levels throughout a substantial portion of the administration period.
- 14. A device according to claim 13 wherein the salt comprises fluoxetine acetate or fluoxetine maleate.
- 15. A device according to claim 13 wherein the reservoir further comprises an anti-irritant.
- 16. A device according to claim 15 wherein the anti-irritant comprises a corticosteroid in an amount effective to coadminister said corticosteroid at a rate in excess of 0.1 μg/cm2·hr throughout the administration period in order to reduce skin irritation wherein the total amount of corticosteroid delivered is less than 5 mg/24 hours.
- 17. A device according to claim 16 wherein the corticosteroid is hydrocortisone.
- 18. A device according to claim 15 further comprising a permeation enhancer.
- 19. A device according to claim 18 wherein the permeation enhancer comprises a monoglyceride or mixture of monoglycerides of a fatty acid.
- 20. A device according to claim 19 further comprising a cosolvent elected from the group consisting of fatty acid esters, lactate esters, and alkyl laurates.
- 21. A device according to claim 20 wherein the monoglyceride is glycerol monolaurate and the cosolvent is selected from the group consisting of dodecyl acetate, lauryl lactate, and methyl laurate.
- 22. A device according to claim 18 wherein the reservoir comprises:
(a) 10 to 50 weight % of a pharmaceutically acceptable salt of fluoxetine; (b) 0.01 to 10 weight % of an anti-irritant; (c) 10-50 weight % of a permeation enhancer; and (d) 20 to 80 weight % polymeric carrier.
- 23. A device according to claim 22 comprising 15 to 40 weight % fluoxetine acetate, 0.1 to 10 weight % hydrocortisone, and 10 to 40 weight % of a permeation enhancer comprising glycerol monolaurate and methyl laurate.
- 24. A device for the transdermal administration of fluoxetine at a therapeutically effective rate, comprising:
(a) a first reservoir comprising an amount of a pharmaceutically acceptable salt of fluoxetine; (b) a second reservoir comprising an excess of fluoxetine salt at or below saturation when in equilibrium with the first reservoir; (c) a rate-controlling membrane between the first reservoir and the second reservoir; (d) a backing behind the body contacting-distal surface of the second reservoir; and (e) means for maintaining the first and second reservoirs in fluoxetine-transmitting relation with a body surface or membrane, said device having a surface area defining an area of fluoxetine delivery of less than about 60 cm2, wherein a therapeutically effective amount of fluoxetine is delivered at a therapeutically effective rate within 250-3200 μg/hr during an administration period of at least 12 hours in order to provide therapeutic blood or plasma levels.
- 25. A device according to claim 24 wherein the salt is fluoxetine acetate or fluoxetine maleate.
- 26. A device according to claim 24 wherein the first reservoir further comprises an anti-irritant.
- 27. A device according to claim 26 wherein the anti-irritant comprises a corticosteroid in an amount effective to coadminister said corticosteroid at a rate in excess of 0.1 μg/cm2·hr throughout the administration period in order to reduce skin irritation wherein the total amount of corticosteroid delivered is less than 5 mg/24 hours.
- 28. A device according to claim 27 wherein the corticosteroid is hydrocortisone.
- 29. A device according to claim 26 wherein the first reservoir further comprises a permeation enhancing amount of a permeation enhancer.
- 30. A device according to claim 29 wherein the permeation enhancer comprises a monoglyceride or mixture of monoglycerides of a fatty acid.
- 31. A device according to claim 30 further comprising a cosolvent selected from the group consisting of fatty acid esters, lactate esters, and alkyl laurates.
- 32. A device according to claim 31 wherein the monoglyceride is glycerol monolaurate and the cosolvent is selected from the group consisting of dodecyl acetate, lauryl lactate, and methyl laurate.
- 33. A device according to claim 29 wherein the first reservoir comprises 15 to 40 weight % fluoxetine acetate, 0.1 to 10 weight % hydrocortisone, and 10 to 40 weight % of a permeation enhancer comprising glycerol monolaurate and methyl laurate.
- 34. A method for the transdermal administration of a drug having a half-life of greater than about 24 hours, comprising:
a) administering the drug to an area of skin in a carrier effective to permit sustained release of the drug at a therapeutically effective rate through the skin during a first predetermined period of time in order to provide therapeutic blood or plasma levels of the drug; b) removing the drug and carrier from the area of skin for a second predetermined period of time of at least 20 hours wherein no additional drug is applied to the skin during the second predetermined time period; c) repeating steps a) and b) for as long as drug therapy is desired wherein therapeutic blood or plasma levels of the drug are achieved during said first predetermined time period and maintained during said second predetermined period and continue to be maintained for as long as therapy is continued.
- 35. A method according to claim 34 wherein the drug is administered by a transdermal delivery device.
- 36. A method according to claim 35 wherein the first predetermined period is from about 24-168 hours.
- 37. A method according to claim 36 wherein the first predetermined period is about 48-120 hours.
- 38. A method according to claim 37 wherein the second predetermined period is about 30-90 hours.
- 39. A method according to claim 38 wherein the drug is fluoxetine or norfluoxetine.
- 40. A method according to claim 39 wherein the drug is a pharmaceutically acceptable salt of fluoxetine and is administered at a rate within the range of 250-3200 μg/hr.
- 41. A method according to claim 40 wherein the pharmaceutically acceptable salt of fluoxetine is administered at a rate within the range of 400-1200 μg/hr.
- 42. A method according to claim 35 further comprising simultaneously coadministering an anti-irritant.
- 43. A method according to claim 42 wherein the anti-irritant comprises a corticosteroid and is administered at a flux of at least 0.1 μg/cm2·hr and the total amount of corticosteroid delivered is less than 5 mg/24 hours.
- 44. A method according to claim 43 wherein the corticosteroid is hydrocortisone.
- 45. A method according to claim 42 further comprising simultaneously coadministering a permeation enhancer.
- 46. A method according to claim 45 wherein the permeation enhancer comprises glycerol monolaurate and methyl laurate.
- 47. A method according to claim 46 wherein the drug is fluoxetine or norfluoxetine and the drug, anti-irritant, and permeation enhancer are administered from a single transdermal delivery device.
RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application Nos. 60/021,727, filed on Jul. 15, 1996 and 60/038,425 filed Feb. 19, 1997.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60021727 |
Jul 1996 |
US |
|
60038425 |
Feb 1997 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
08892118 |
Jul 1997 |
US |
Child |
10302490 |
Nov 2002 |
US |