Novel formulations for the administration of fluoxetine

Abstract

Composition of matter for application to a body surface or membrane to administer fluoxetine by permeation through the body surface or membrane, the composition comprising fluoxetine to be administered, at a therapeutically effective rate, alone or in combination with a permeation enhancer or mixture. A preferred embodiment is directed to the transdermal administration of fluoxetine at reduced skin irritation levels wherein fluoxetine, preferably provided as fluoxetine acetate, is coadministered with a corticosteroid such as hydrocortisone. Also disclosed are drug delivery devices containing the fluoxetine or fluoxetine and enhancer composition and methods for the transdermal administration of the fluoxetine and fluoxetine/enhancer composition.

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 through a body surface or mucosal membrane 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 that can achieve the therapeutically effective rate with a surface area of less than 60 cm 2  contacting body surface or mucosal membrane 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/cm 2  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 - 47 . (canceled)  
     
     
         48 . A composition according to  claim 2  wherein the composition results in less irritation than a composition using fluoxetine base to delivering the therapeutic level.  
     
     
         49 . A composition according to  claim 2  wherein the composition comprises fluoxetine acetate or fluoxetine maleate and results in less irritation than a composition using fluoxetine base to delivering the therapeutic level.  
     
     
         50 . A composition according to  claim 2  wherein the composition is disposed on a backing in a transdermal drug delivery patch, the composition results in less irritation than a composition using fluoxetine base to delivering the therapeutic level.  
     
     
         51 . 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 through an area of less than 60 cm 2  contacting body surface or mucosal membrane in order to administer therethrough a therapeutically effective amount of fluoxetine to achieve and maintain therapeutic blood or plasma levels throughout a substantial portion of the administration period with reduced irritation than a composition using fluoxetine base, and 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.