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[0323] Since PPA-HCl is a salt of a free base, it reacts with Na$_{2}$COy The concentration ofN a$_{2}$CO$_{3 }$in the system after the reaction is completed depends on the amount of PPA-HCl added. The remaining sodium carbonate concentration after the reaction is completed is defined as "excess Na$_{2}$CO$_{3 }$ con› centration," which is defined by the following equation. 

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The excess Na$_{2}$CO$_{3 }$ for these four PPA-HCl systems was calculated, and the pH was measured as described in the Methods section. The pH of the PPA-HCl patch increased from 9.81 to 10.17 when the calculated excess Na$_{2}$CO$_{3 }$ con› centration in the dried patch was increased from 0.4% to 16.7%. 

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[0324] The cumulative amount of PPA-HCl across human cadaver skin was calculated using the measured PPA-HCl concentrations in the receiver solutions. 

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[0325] Even though patch PPA-6 contained 13.2% Na$_{2}$CO$_{3}$ , the cumulative amount of PPA-HCl that permeated across the human cadaver skin at 24 hours ( 410.4 µg/ cm 2 ) was lower than that from the formulation without Na$_{2}$CO$_{3 }$ (PPA- 5, 545.1 µg/cm 2 ). This may be due to the consumption of Na$_{2}$CO$_{3 }$ by the reaction between Na$_{2}$CO$_{3 }$ and PPA-HCl, which reduced the Na$_{2}$CO$_{3 }$ concentration to only 0.4% as the excess Na$_{2}$CO$_{3 }$ concentration. 

[0326] When the calculated excess Na$_{2}$CO$_{3 }$ concentration in the dried patch was further increased from O .4 % to 16. 7%, the cumulative amount of PPA-HCl that permeated across the human cadaver skin at 24 hours was increased from 410.4 to 114 7 .5 µg/cm 2 . This result indicated that the permeation of PPA-HCl could be enhanced by Na$_{2}$CO$_{3}$ , even though the required excess Na$_{2}$CO$_{3 }$ concentration is higher than that of NaOH. Greater amounts of Na$_{2}$CO$_{3 }$ may be necessary because it is a weaker base compared to NaOH and the molecular weight of Na$_{2}$CO$_{3 }$ is higher than that of NaOH. The formulation of PPA-7 provided up to 1.3-fold more phe› nylpropanolamine hydrochloride flux than in the absence of Na$_{2}$CO$_{3 }$ (PPA-PCl). The highest pH formulation evaluated, PPA-8, provided up to 2-foldmore flux than in the absence of Na$_{2}$CO$_{3}$ . 

[0327] An in vitro skin permeation study was conducted using four phenylpropanolamine hydrochloride transdermal systems, designated PPA-9, PPA-10, PPA-11, and PPA-12, the compositions of which are set forth in Table 19. The matrix patches were prepared and evaluated using the same procedures as set forth in Example 3. The theoretical percent weight for each ingredient after drying ( calculated assuming all the volatile ingredients were completely removed during drying) is listed in Table 20. 

## Example 7 

