content_image/935819.jpg content_image/935822.jpg content_image/935824.jpg content_image/935820.jpg content_image/935823.jpg content_image/935825.jpg
the measured lidocaine concentrations in the receiver solu› tions. 

<img src='content_image/935819.jpg'>

[0461] The pH of the patches was measured as described in the Methods section but using a 2.4 cm 2 circular patch. 

<img src='content_image/935822.jpg'>

[0462] The pH of the lidocaine patch measured increased from 8.86 to 10.87 when the calculated excess NaOH concentration 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 concen› tration in the dried patch was increased from 0% to 4.6%. 

[0463] The formulation of Lido-2 provided up to 1.5-fold more lidocaine flux than in the absence of NaOH (Lido-1). The highest pH formulation evaluated, Lido-3, provided up to 3-fold more flux than in the absence of NaOH. 

[0464] 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. 

[0465] 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. 

[0466] 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. 

<img src='content_image/935824.jpg'>

## Example 26 

<img src='content_image/935820.jpg'>

[0467] 

<img src='content_image/935823.jpg'>

[0468] 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. 

<img src='content_image/935825.jpg'>

[0469] 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. 

