Method for transdermal delivery of permeant substances

Abstract

A method for delivering permeant substances transdermally into a membrane of an animal includes forming at least one delivery opening in the skin tissue, with the at least one delivery opening having a mean opening depth of between about 40 and about 90 microns.

We claim: 
     
         1 . A method for delivering permeant substances through a biological membrane of an animal comprising forming a plurality of delivery openings in the membrane, wherein an opening depth of the majority of said delivery openings falls within the range between 40 and 90 microns, and delivering a permeant through the plurality of delivery openings by placing a patch comprising the permeant over the plurality of delivery openings,
 wherein the plurality of delivery openings are formed by microporation conducted with positive pressure being present between a microporator and said membrane, wherein said positive pressure results from a vacuum of about 0.25 to about 0.80 bar being applied between said microporator and said membrane.   
     
     
         2 . The method of  claim 1  wherein the opening depth of a majority of said delivery openings falls within the range of 50 to 70 microns. 
     
     
         3 . The method of  claim 2  wherein 75% of said delivery openings have an opening depth falling within the range of 50 to 70 microns. 
     
     
         4 . The method of  claim 1  wherein said delivery openings have a range of opening depths falling within one standard deviation of 50 microns to 70 microns. 
     
     
         5 . The method of  claim 1  wherein said delivery openings have a range of opening depths falling within one standard deviation of 90 microns. 
     
     
         6 . The method of  claim 1  wherein the plurality of delivery openings are formed by a planar array microporation device. 
     
     
         7 . The method of  claim 1  wherein the plurality of delivery openings are formed by a microporator selected from the group consisting of a heated probe element capable of conductively delivering thermal energy via direct contact to a biological membrane to cause the ablation of some portion of the membrane deep enough to form a micropore, the heated probe comprising an electrically heated resistive element capable of ablating a biological membrane or an optically heated topical dye/absorber layer, electro-mechanical actuator, a microlancet, an array of microneedles (solid or hollow), microprojections, microcstructures or lancets, a sonic energy ablator, a laser ablation system, and a high pressure fluid jet puncturer. 
     
     
         8 . The method of  claim 1  wherein said positive pressure results from a vacuum of about 0.50 bar being applied between said device and said membrane. 
     
     
         9 . The method of  claim 1  wherein said delivery openings have a distribution resulting in a bell-shaped curve with said delivery openings having a mean opening depth of between 40 and 90 microns. 
     
     
         10 . A method for evaluating the effectiveness of a microporator comprising the steps of: forming at least one delivery opening in a biological membrane of a mammal using said microporator, delivering a permeant substance across the area of the membrane with said at least one delivery opening, measuring the steady state serum concentration for said permeant substance, measuring the trans-epidermal water loss across the membrane of the mammal, and comparing the results of said measurements with known values for each which provide desired results. 
     
     
         11 . The method of  claim 10  wherein said at least one delivery opening has a mean opening depth of between about 40 and about 90 microns. 
     
     
         12 . The method of  claim 10  wherein a plurality of delivery openings are formed in the biological membrane, the opening depth of a majority of said delivery openings falling within the range of about 40 and about 90 microns. 
     
     
         13 . The method of  claim 12  wherein 75% of said delivery openings have an opening depth falling within the range of about 50 to about 70 microns. 
     
     
         14 . The method of  claim 12  wherein said delivery openings have a range of opening depths falling within one standard deviation of about 50 microns to about 70 microns. 
     
     
         15 . The method of  claim 10  wherein said delivery openings have a range of opening depths falling within one standard deviation of about 90 microns. 
     
     
         16 . The method of  claim 10  wherein said at least one delivery opening is formed by a planar array microporation device. 
     
     
         17 . The method of  claim 10  wherein said at least one delivery opening is formed by a microporator selected from the group consisting of a heated probe element capable of conductively delivering thermal energy via direct contact to a biological membrane to cause the ablation of some portion of the membrane deep enough to form a micropore, the heated probe comprising an electrically heated resistive element capable of ablating a biological membrane or an optically heated topical dye/absorber layer, electromechanical actuator, a microlancet, an array of microneedles (solid or hollow), microprojections, microcstructures or lancets, a sonic energy ablator, a laser ablation system, and a high pressure fluid jet puncturer. 
     
     
         18 . The method of  claim 10  wherein said biological membrane is skin. 
     
     
         19 . The method of  claim 12  wherein said delivery openings have a distribution resulting in a bell-shaped curve with said delivery openings having a mean opening depth of between 40 and 90 microns.