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[0453] An in vitro skin permeation study was conducted using three enalapril maleate transdermal systems, desig› nated Enal-1, Enal-2 and Enal-3, the compositions of which are set forth in Table 90. 

[0454] Round disc samples were prepared as described in the Methods section, except that the formulation was dried at a temperature of 65° C. and the discs were cut into discs having a diameter of 9 /26 inch. 

[0455] The theoretical percent weight for each ingredient after drying ( calculated assuming all volatile ingredients were completely removed during drying) is set forth in Table 91. 

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[0456] 

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[0457] Since enalapril maleate is an acid addition salt of a free base, it reacts with NaOH. The concentration of NaOH in the system after the reaction is completed depends on the amount of enalapril maleate added. The remaining NaOH concentration after the reaction is completed is defined as the excess NaOH concentration, and was calculated as described in Example 2. The pH of each patch was measured as described in the Methods section but using a 2.4 cm 2 circular patch. The pH of the enalapril maleate patch increased from 7.29 to 10.82 when the calculated excess NaOH concentration in the dried patch was increased from 1.9% to 6.9%. The pH of the patch without NaOH was 3.12. 

## Example 26 

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[0458] The in vitro permeation of enalapril maleate through human cadaver skin from these discs was measured as described in the Methods section. Three diffusion cells were used for each formulation. The receiver solution, 10% ethanol, was completely withdrawn and replaced with fresh receiver solution at each time point. The samples taken were analyzed by an HPLC for the concentration of enalapril maleate in the receiver solution. The cumulative amount of enalapril maleate that permeated across the human cadaver skin was calculated using the measured enalapril maleate concentrations in the receiver solutions. 

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[0459] The cumulative amount of enalapril maleate across human cadaver skin at 24 hours increased from 0.029 mg/cm $^{2 }$to 1.826 mg/cm $^{2 }$when the calculated excess NaOH concentration in the dried patch was increased from 1.9% to 6.9% as compared to undetectable flux for the formulation without NaOH. The formulation of Enal-3 provided up to 63-fold more enalapril maleate flux than the formulation of Enal-2. 

[0460] All patents, publications, and other published documents mentioned or referred to in this specification are herein incorporated by reference in their entirety. 

[0461] It is to be understood that while the invention has been described in conjunction with the preferred specific embodiments hereof, the foregoing description, as well as the examples which are intended to illustrate and not limit the scope of the invention, it should be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the scope of the invention. Other aspects, advantages and modi› fications will be apparent to those skilled in the art to which the invention pertains. 

[0462] Accordingly, the scope of the invention should therefore be determined with reference to the appended claims, along with the full range of equivalents to which those claims are entitled. 

We claim: 

1. A method for enhancing the flux of an analgesic agent through a body surface, comprising: 

( a) administering the analgesic agent to a localized region of a human patient’s body surface; and 

