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[ 0414] Since the reaction between risperidone and N aO H is not expected to be significant, the concentration ofNaOH in the system is assumed to be independent from the amount of risperidone added. Therefore, the NaOH concentration listed in Table 71 equals the excess Na OH concentration, defined as described in Example 2. 

[0415] The pH of the patches was measured as described in the Methods section, but using a 2.4 cm 2 cm circular patch. The pH of the risperidone patch measured increased from 7.98 to 10.15 when the calculated excess NaOH concentra› tion in the dried patch was increased from 0% to 1. 7%. 

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[0416] The in vitro permeation of risperidone 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solution, 5% ethanol/ 95% PBS buffer (0.05 M KH$_{2}$PO$_{4 }$ with 0.15 M NaCl, pH adjusted to 6.5), was completely withdrawn and replaced with fresh receiver solution at each time point.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 ofrisperi› done in the receiver solution. The cumulative amount of ris› peridone across human cadaver skin was calculated using the measured risperidone concentrations in the receiver solu› tions. 

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[0417] The cumulative amount of risperidone across human cadaver skin at 24 hours increased from O .009 mg/ cm 2 to 0.312 mg/cm $^{2 }$when the calculated excess NaOH concen› tration in the dried patch was increased from 0% to 1.7%. 

[0418] The formulation ofRispe-2 provided up to 15-fold more risperidone flux than in the absence ofNaOH (Rispe-1 ). The highest pH formulation evaluated, Rispe-3, provided up to 35-fold more flux than in the absence ofNaOH. 

[0419] An in vitro skin permeation study was conducted using three paroxetine hydrochloride transdermal systems, designated Pax-1, Pax-2 and Pax-3, the compositions of which are set forth in Table 74. 

[0420] Round disc samples were prepared in a manner similar to that 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. 

[0421] The theoretical percent weight for each ingredient after drying ( calculated assuming all volatile ingredients were completely removed during drying) is set forth in Table 75. 

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[0422] Since paroxetine HCl 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 

## Example 22 

