Novel formulations for transdermal delivery of pergolide

Abstract

Composition of matter for application to a body surface or membrane to administer pergolide by permeation through the body surface or membrane, the composition comprising pergolide to be administered, at a therapeutically effective rate, alone or in combination with a permeation enhancer or mixture. Also disclosed are drug delivery devices containing the pergolide or pergolide and enhancer composition and methods for the transdermal administration of the pergolide and pergolide/enhancer composition.

1 . A composition of matter for transdermally delivering pergolide through intact skin by permeation therethrough, the composition comprising an amount of at least one material selected from the group consisting of pergolide and a pharmaceutically acceptable salt of pergolide in a carrier effective to permit sustained release of said material at a therapeutically effective rate over an administration period of at least about 8 hours in order to achieve therapeutically effective blood plasma levels of pergolide in a patient over a substantial portion of said administration period.  
     
     
         2 - 42 . Cancelled.  
     
     
         43 . A device for the transdermal administration of pergolide mesylate through intact skin at a therapeutically effective rate, comprising: 
 (a) a reservoir comprising an amount of pergolide mesylate and at least one permeation enhancer in an amount sufficient to substantially increase the permeability of the intact skin to pergolide mesylate throughout a substantial portion of the administration period;    (b) a backing on or adjacent the body contacting-distal surface of the reservoir; and    (c) means for maintaining the reservoir in drug and permeation enhancer transmitting relation with the intact skin wherein pergolide mesylate is delivered at a therapeutically effective rate for an administration period of at least 8 hours in order to provide therapeutically effective blood plasma levels of pergolide in a patient over a substantial portion of said administration period.    
     
     
         44 . A method for the transdermal administration of pergolide mesylate by permeation through intact skin at a therapeutically effective rate, which method comprises: 
 (a) administering pergolide mesylate to a body surface or membrane in a carrier effective to permit sustained release of pergolide mesylate through the intact skin;    (b) simultaneously coadministering a permeation-enhancing amount of a permeation enhancer selected from the group consisting of lauramide diethanolamine, monoglycerides or mixtures of monoglycerides of fatty acids, esters of C 10 -C 20  fatty acids, lactate esters, caproyl lactic acid, C 2 -C 4  alcohols, dimethyl lauramide, polyethylene glycol monolaurate, polyethylene glycol-4 lauryl ether, and mixtures thereof, in an amount sufficient to substantially increase the permeability of the body surface or membrane to pergolide throughout a substantial portion of the administration period;    wherein pergolide is administered at a therapeutically effective rate of at least about 1 μg/cm 2 hr for an administration period of at least 8 hours in order to administer about 1.5 to 8 mg of pergolide per day in order to provide therapeutically effective blood plasma levels of pergolide in a patient over a substantial portion of said administration period.    
     
     
         45 . A composition according to  claim 1  wherein the therapeutically effective blood plasma level is at least about 100 pg/ml.  
     
     
         46 . A composition according to claim I wherein the therapeutically effective blood plasma level is about 300-1200 pg/ml.  
     
     
         47 . A composition according to  claim 1  wherein said therapeutically effective rate is about 1.5 mg to about 8.0 mg per day.  
     
     
         48 . A composition according to  claim 1  wherein said composition is the form selected from the group consisting of ointment, gel, cream, lotion and liquid.  
     
     
         49 . A composition according to  claim 43  wherein the permeation enhancer is selected from the group consisting of lauramide diethanolamine, glycerol monolaurate, glycerol monooleate, lactate esters, caproyl lactic acid, ethanol, and polyethylene glycol-4 lauryl ether, alone or in combinations of two or more.  
     
     
         50 . A composition according to  claim 43  wherein the therapeutically effective blood plasma level is at least about 100 pg/ml.  
     
     
         51 . A composition according to  claim 43  wherein the therapeutically effective blood plasma level is about 300-1200 pg/ml.  
     
     
         52 . A composition according to  claim 44  wherein the therapeutically effective blood plasma level is at least about 100 pg/ml.  
     
     
         53 . A composition according to  claim 44  wherein the therapeutically effective blood plasma level is about 300-1200 pg/ml.