Aug. 30, 2012  39  US 2012/0220962 Al  TABLE 60-continued  TABLE 61  TABLE 64  TABLE 62  TABLE 65  TABLE 63  cells was measured by removing the receiving fluid, remov› ing the clamp and the donor chamber, gently teasing the patch  away from the skin with tweezers, leaving the skin on the  receiver chamber, measuring the pH of the solution on the  skin by placing the microelectrode directly onto the skin  surface.  [0397]  The cumulative amount of diclofenac sodium across  human cadaver skin was calculated using the measured  diclofenac sodium concentrations in the receiver solutions.  [0393]  Since diclofenac sodium is not expected to react  withNaOH, theNaOHconcentrationlistedin Table61 equals  the excess NaOH concentration, calculated as described in  Example 2.  [0394]  The pHs of the receiver solutions at various time  points are listed below.  [0398]  The cumulative amount of diclofenac sodium across  human cadaver skin at 24 hours increased from 34.6 µg/cm 2  to 3257.7 µg/cm $^{2 }$when the calculated excess NaOH concen› tration in the dried patch was increased from 0% to 1.8%. The  cumulative amount of diclofenac sodium across human  cadaver skin at 24 hours from the system containing 0.4%  NaOH (Diclo-0) was 227.7 µg/cm 2 ,  which was about six  times higher than that from the formulation without NaOH  (34.6 µg/cm 2 ,  Diclo-9). This result indicated that the perme› ation of diclofenac sodium across human skin could be  enhanced by a NaOH concentration as low as 0.4%.  [0399]  The formulation of Diclo-10 provided up to 7-fold  more diclofenac sodium flux than in the absence of NaOH  (Diclo-9). The formulation of Diclo-11 provided up to  50-fold more flux, while the highest pH formulation evalu› ated, Diclo-12, provided up to 94-fold more flux than in the  absence ofNaOH.  [0400]  The measured pHs at the skin/patch interface are  listed below.  [0395]  The pH of the patches was measured as described in  the Methods section. The pH of the diclofenac sodium patch  increased from 7.40 to 10.38 when the calculated excess  NaOH concentration in the dried patch was increased from  0%to 1.8%.  [0396]  The in vitro permeation of diclofenac sodium  through human cadaver skin from these discs was measured  as described in the Methods section. Twelve diffusion cells  were used for each formulation. The cells were filled with  10% ethanol/90% water solution. At each time point, the pH  at the interface between skin and the patch for three diffusion  Component Weight and Weight Percent  Based on Dried Film Weight  Diclo-9  Diclo-10  Diclo-11  Diclo-12  g(wt%)  g(wt%)  g(wt%)  g(wt%)  Diclofenac  0.6 (22.2)  0.6 (22.1)  0.9 (22.1)  0.6 (21.8)  sodiwn  PG  0.9 (33.3)  0.9 (33.2)  0.9 (33.1)  0.9 (32.7)  NaOH  0  0.01 (0.4)  0.02 (0.7)  0.05 (1.8)  PIB adhesive  1.2 (44.4)  1.2 (44.3)  1.2 (44.1)  1.2 (43.6)  (30% solid)  Time  3 hours  6 hours  lOhours  24hours  pH of Receiver Solutions  Diclo-9  Diclo-10  Diclo-11  8.1  8.0  9.3  7.4  7.9  7.7  7.0  7.6  7.3  7.0  8.9  7.5  Diclo-12  10.8  10.0  7.7  9.6  ExcessNaOH  Concentration  pH  Excess NaOH Concentration (wt%) and pH  Diclo-9  0  7.40  Diclo-10  0.4  8.99  Diclo-11  0.7  10.71  Diclo-12  1.8  10.38  Component Weight and Weight Percent Based on Total Solution Weight  Diclo-9  Diclo-10  Diclo-11  g(wt%)  g(wt%)  g(wt%)  NaOH  0  0.01 (0.2)  0.02 (0.3)  PIB adhesive  4 (61.5)  4 (61.3)  4 (61.2)  (30% solid)  Heptane  (15.4)  (15.3)  1 (15.3)  DI water  0  0.01 (0.2)  0.02 (0.3)  Diclo-12  g(wt%)  0.05 (0.8)  4 (60.6)  0.05  (15.2)  (0.8)  Cumulative Amount ofDiclofenac Sodium (µg/cm 2 )  Time  3 hours  6 hours  10 hours  24 hours  Diclo-9  7.5  39.6  63.2  34.6  Diclo-10  1.5  18.3  49.3  227.7  Diclo-11  33.4  269.3  654.4  1733.8  Diclo-12  257.7  793.3  1652.2  3257.7  Time  3 hours  6 hours  10 hours  24 hours  pHs at the Interface between Skin and Patch  Diclo-9  8.5  Diclo-10  11.0  11.0  10.9  9.7  Diclo-11  11.2  10.7  10.1  Diclo-12  10.3  9.8  10.2  9.4  *  Could not be measured because there was not enough solution at the interface. 