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[0306] Ten healthy human subjects were included in the skin irritation study. Each subject wore seven patches listed above on the arms for 24 hours. An adhesive film with a diameter of7/s inch was applied over each system on the skin except the petrolatum patch to secure the system and to make the system occlusive for 24 hours. After 24 hours, the patches were removed and the skin was scored on a 0-4 scale. The scoring scale employed is listed below. The skin was scored again at 48 hours. 

[0307] 0=negative 

[0308] 2=erythema and induration 

[0309] +=equivocal reaction (0.5) 

[0310] 3=erythema, induration and vesicles 

[0311] l=erythema 

[0312] 4=bullae 

[0313] The in vitro permeation of ketoprofen through human cadaver skin from formulations Keto-7, Keto-8, Keto- 9, and Keto-10, was measured as described in the Methods section. Three diffusion cells were used for each formulation. 

[0314] Normal saline was used as the receiver solution. The receiver solution was collected at 24 hours and analyzed by an HPLC for the concentration of ketoprofen. The cumulative amount of ketoprofen that permeated across the human cadaver skin at 24 hours, was calculated using the measured ketoprofen concentrations in the receiver solutions. The excess NaOH concentrations for these four ketoprofen sys› tems, were calculated as described in Example 2, and the pH of the patches was measured as described in the Methods section. 

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[0315] The cumulative amount of ketoprofen that perme› ated across the human cadaver skin at 24 hours increased from 0.17 mg/cm$^{2 }$to 1.52 mg/cm$^{2 }$when the calculated excess NaOH concentration in the dried patch was increased from 3.22% to 5.01 %. The excess NaOH concentration and the cumulative amount ofketoprofen across skin at 24 hours and the patch pH for Keto-8 was 0.34 mg/cm $^{2 }$and 10.81 respec› tively, which was about the same as those for Keto-3 shown in Example 2 (0.32 mg/cm 2 , pH=l0.10). However, the excess Na OH concentration for Keto-8 (3.92%) was higher than that for Keto-3 (1.00% ), which may be due to the consumption of NaOH through reactions between NaOH and components other than ketoprofen in the Keto-8 formulation. 

[0316] The irritation scores obtained indicate that irritation from this patch was insignificant. 

[0317] The formulation of Keto-8 provided up to 2-fold more ketoprofen flux than the lowest pH formulation evalu› ated (Keto-7). The formulation of Keto-9 provided up to 3-fold more flux, while the highest pH formulation evaluated, Keto- I 0, provided up to 9-fold more flux than in the absence ofNaOH. 

