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[0444] Since the reaction between lidocaine and NaOH is not expected to be significant, the concentration ofNaOH in the system is assumed to be independent from the amount of lidocaine added. Therefore, the NaOH concentration listed in Table 87 equals the excess Na OH concentration, calculated as described in Example 2. 

[0445] The in vitro permeation oflidocaine 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solution, 5% ethanol/95% PBS buffer (0.05 M KH$_{2}$PO$_{4 }$ with 0.15 M NaCl, pH adjusted to 6.5), was completely withdrawn and replaced with fresh receiver solution at each time point. The samples taken were analyzed by an HPLC for the concentration oflidocaine in the receiver solution. The cumulative amount oflidocaine across human cadaver skin was calculated using the measured lidocaine concentrations in the receiver solutions. 

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[0446] The pH of the patches was measured as described in the Methods section but using a 2.4 cm.sup.2 circular patch. 

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[0447] The pH of the lidocaine patch measured increased from 8.86 to 10.87 when the calculated excess NaOH con› centration in the dried patch was increased from 0% to 4.6%. The cumulative amount of lidocaine across human cadaver skin at 24 hours increased from 0.428 mg/cm 2 to 1.169 mg/cm $^{2 }$when the calculated excess NaOH concentration in the dried patch was increased from 0% to 4.6%. 

[0448] The formulation ofLido-2 provided up to 1.5-fold more lidocaine flux than in the absence of NaOH (Lido-I). The highest pH formulation evaluated, Lido-3, provided up to 3-fold more flux than in the absence ofNaOH. 

[0449] 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. 

[0450] 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 /16 inch. 

[0451] 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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[0452] Since enalapril maleate is an acid addition salt of a free base, it reacts with NaOH. The concentration ofNaOH 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 concentra› tion in the dried patch was increased from 1.9% to 6.9%. The pH of the patch without NaOH was 3.12. 

## Example 26 

