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[0303] The excess NaOH concentrations for these four ibuprofen gels, were calculated as described in Example 2, and the pH of the gels was directly measured using a pH meter. The pH of the ibuprofen gel (determined using the procedures of the previous examples) increased from 6.58 to 12.22 when the calculated excess NaOH concentration in the gel was increased from 0% to 1.74%. The skin irritation could be related to the pH of the gel, which depends on the excess NaOH concentration. 

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[0304] The in vitro permeation of ibuprofen through human cadaver skin from these gels was measured in a slightly different manner than as described in the Methods section. Three diffusion cells were used for each formula› tion. Normal saline was used as the receiver solution. The entire receiver solution was collected and replaced with fresh saline at each time point. The receiver solution col› lected was analyzed by an HPLC for the concentration of ibuprofen. The cumulative amount of ibuprofen across human cadaver skin was calculated using the measured ibuprofen concentrations in the receiver solutions, which were plotted versus time and are described below. 

[0305] The cumulative amount of ibuprofen across human cadaver skin at 24 hours increased from 0.33 mg/cm $^{2 }$to 5.74 mg/cm 2 when the calculated excess NaOH concentration in the gel was increased from 0% to 1.74% (Ibu-4), i.e., up to about 17-fold more flux was obtained than with the formu› lation having 0% excess NaOH concentration. The cumu› lative amount of ibuprofen that permeated across the human cadaver skin at 24 hours from the formulation with an excess NaOH concentration of0.98% (Ibu-3, 1.12 mg/cm 2 ) is about 3 times higher than that from the formulation with an excess NaOH concentration of 0% (Ibu-2, 0.33 mg/cm 2 ). 

[0306] An in vitro skin permeation study was conducted using four phenylpropanolamine hydrochloride transdermal systems, designated PPA-5, PPA-6, PPA-7, and PPA-8, the compositions of which are set forth in Table 15. The matrix patches were prepared and evaluated using the same proce- 

## Example 6 

dures 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 16. 

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[0307] 

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[0308] Since PPA-HCl is a salt of a free base, it reacts with Na$_{2}$CO$_{3}$ . The concentration of Na$_{2}$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$_{3 }$ concentration," which is defined by the following equation. 

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[0309] The excess Na$_{2}$ CO$_{3 }$ for these four PPA-HCl sys› tems 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 CO$_{3 }$ concentration in the dried patch was increased from o.4’% to 16.7%. 

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[0310] The cumulative amount of PPA-HCl across human cadaver skin was calculated using the measured PPA-HCl concentrations in the receiver solutions. 

