Aug. 30, 2012  26  US 2012/0220962 Al  TABLE 10  TABLE 11  TABLE 12  [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.  [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.  Component Weight and Weight Percent Based on Total Solution Weight  Keto-7  Keto-8  Keto-9  Keto-10  g(wt%)  g(wt%)  g(wt%)  g(wt%)  Ketoprofen  2.4 (14.0)  2.4 (14.0)  2.4 (13.9)  2.4 (13.8)  NaOH  0.6 (3.5)  0.65 (3.8)  0.69 (4.0)  0.73 (4.2)  DI water  0.6 (3.5)  0.65 (3.8)  0.69 (4.0)  0.73 (4.2)  Tetraglycol  0.5 (2.9)  0.5 (2.9)  0.5 (2.9)  0.5 (2.9)  Isopropyl myristate  0.4 (2.3)  0.4 (2.3)  0.4 (2.3)  0.4 (2.3)  Methyl salicylates  0.6 (3.5)  0.6 (3.5)  0.6 (3.5)  0.6 (3.5)  Methylal  4 (23.4)  4 (23.3)  4 (23.3)  4 (23.0)  PIB adhesive  8 (46.8)  8 (46.5)  8 (46.3)  8 (46.1)  (30% solid)  Weight and Theoretical Weight Percent Based on Dried Film Weight  Keto-7  Keto-8  Keto-9  g(wt%)  g(wt%)  g(wt%)  Ketoprofen  2.4 (34.8)  2.4 (34.5)  2.4 (34.3)  NaOH  0.6 (8.7)  0.65 (9.4)  0.69 (9.9)  PIB adhesive  2.4 (34.0)  2.4 (34.5)  2.4 (34.3)  Tetraglycol  0.5 (7.2)  0.5 (7.2)  0.5 (7.2)  Isopropyl myristate  0.4 (5.8)  0.4 (5.8)  0.4 (5.7)  Methyl salicylates  0.6 (8.7)  0.6 (8.6)  0.6 (8.6)  Keto-10  g(wt%)  2.4 (34.1)  0.73 (10.4)  2.4 (34.1)  0.5 (7.1)  0.4 (5.7)  0.6 (8.5)  Excess NaOH Concentration (wt%), Cumulative  Permeation Amount (mg/cm 2 ),  pH  Keto-7  Keto-8  Keto-9  Excess NaOH  3.22%  3.92%  4.47%  Concentration  Cumulative  0.17  0.34  0.54  permeation amount  PH  10.06  10.81  11.04  Keto-10  5.01%  1.52  11.18 