Jun.5,2003  39  US 2003/0104041 Al  TABLE  60  TABLE  61  TABLE  62  TABLE  64  TABLE  63  Component Weight and Weight Percent Based on Total Solution Weight  Diclo-9  Diclo-10  Diclo-11  Diclo-12  g(wt%)  g (wt%)  g(wt%)  g(wt%)  Diclofenac sodium  0.6 (9.2)  0.6 (9.2)  0.9 (9.2)  0.6 (9.1)  PG  0.9 (13.8)  0.9 (13.8)  0.9 (13.8)  0.9 (13.6)  NaOH  0  0.01 (0.2)  0.02 (0.3)  0.05 (0.8)  PIE adhesive  4 (61.5)  4 (61.3)  4 (61.2)  4 (60.6)  (30% solid)  Heptane  1 (15.4)  (15.3)  1 (15.3)  1 (15.2)  DI water  0  0.01 (0.2)  0.02 (0.3)  0.05 (0.8)  [0395]  Component Weight and Weight Percent Based on Dried Film Weight  Diclo-9  Diclo-10  Diclo-11  g(wt%)  g (wt%)  g(wt%)  Diclofenac sodium  0.6 (22.2)  0.6 (22.1)  0.9 (22.1)  PG  0.9 (33.3)  0.9 (33.2)  0.9 (33.1)  NaOH  0  0.01 (0.4)  0.02 (0.7)  PIE adhesive  1.2 (44.4)  1.2 (44.3)  1.2 (44.1)  (30% solid)  Diclo-12  g(wt%)  0.6 (21.8)  0.9 (32.7)  0.05 (1.8)  1.2 (43.6)  pH of Receiver Solutions  Time  Diclo-9  Diclo-10  Diclo-11  Diclo-12  3 hours  8.1  8.0  9.3  10.8  6 hours  7.4  7.9  7.7  10.0  10 hours  7.0  7.6  7.3  7.7  24 hours  7.0  8.9  7.5  9.6  Cumulative Amount of Diclofenac Sodium  (µg/cm 2 )  Time  Diclo-9  Diclo-10  Diclo-11  Diclo-12  3 hours  7.5  1.5  33.4  257.7  6 hours  39.6  18.3  269.3  793.3  10 hours  63.2  49.3  654.4  1652.2  24 hours  34.6  227.7  1733.8  3257.7  Excess NaOH  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  [0396]  Since diclofenac sodium is not expected to react  with NaOH, the NaOH concentration listed in Table 61  equals the  excess NaOH concentration, calculated as  described in Example 2.  [0397]  The pHs of the receiver solutions at various time  points are listed below.  [0398]  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%.  [0399]  The in vitro permeation of diclofenac sodium  through human cadaver skin from these discs was measured  [0401]  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  concentration 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-10) 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  [0400]  The cumulative amount of diclofenac sodium  across human cadaver skin was calculated using the mea› sured diclofenac sodium concentrations in the receiver solu› tions.  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  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. 