Aug. 30, 2012  28  US 2012/0220962 Al  [0323]  Since PPA-HCl is a salt of a free base, it reacts with  Na$_{2}$COy The concentration ofN a$_{2}$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$_{3 }$ con› centration," which is defined by the following equation.  The excess Na$_{2}$CO$_{3 }$ for these four PPA-HCl systems 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$_{2}$CO$_{3 }$ con› centration in the dried patch was increased from 0.4% to  16.7%.  [N  a2CO3exmJ~  [N  a2CO3,a,a/J- [N  a2C03needed for neu- tralization]  [0324]  The cumulative amount of PPA-HCl across human  cadaver skin was calculated using the measured PPA-HCl  concentrations in the receiver solutions.  [0325]  Even though patch PPA-6  contained  13.2%  Na$_{2}$CO$_{3}$ , the cumulative amount of PPA-HCl that permeated  across the human cadaver skin at 24 hours ( 410.4 µg/  cm  2 )  was  lower than that from the formulation without Na$_{2}$CO$_{3 }$ (PPA- 5, 545.1 µg/cm 2 ).  This may be due to the consumption of  Na$_{2}$CO$_{3 }$ by the reaction between Na$_{2}$CO$_{3 }$ and PPA-HCl,  which reduced the Na$_{2}$CO$_{3 }$ concentration to only 0.4% as the  excess Na$_{2}$CO$_{3 }$ concentration.  [0326]  When the calculated excess Na$_{2}$CO$_{3 }$ concentration  in the dried patch was further increased from  O  .4 % to 16. 7%,  the cumulative amount of PPA-HCl that permeated across the  human cadaver skin at 24 hours was increased from 410.4 to  114 7 .5 µg/cm 2 .  This result indicated that the permeation of  PPA-HCl could be enhanced by Na$_{2}$CO$_{3}$ ,  even though the  required excess Na$_{2}$CO$_{3 }$ concentration is higher than that of  NaOH. Greater amounts of Na$_{2}$CO$_{3 }$ may be necessary  because it is a weaker base compared to NaOH and the  molecular weight of Na$_{2}$CO$_{3 }$ is higher than that of NaOH.  The formulation of PPA-7 provided up to 1.3-fold more phe› nylpropanolamine hydrochloride flux than in the absence of  Na$_{2}$CO$_{3 }$ (PPA-PCl). The highest pH formulation evaluated,  PPA-8, provided up to 2-foldmore flux than in the absence of  Na$_{2}$CO$_{3}$ .  [0327]  An in vitro skin permeation study was conducted  using four phenylpropanolamine hydrochloride transdermal  systems, designated PPA-9, PPA-10, PPA-11, and PPA-12,  the compositions of which are set forth in Table 19. The  matrix patches were prepared and evaluated using the same  procedures 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 20.  Example 7  TABLE IS-continued  TABLE 19  TABLE 18  TABLE 17  Excess Na 2 CO 3  Concentration (wt%) and pH  Excess Na 2 CO 3  Concentration  pH  PPA-5  6.54  PPA-6  0.4%  9.81  PPA-7  6.7%  9.86  PPA-8  16.7%  10.17  Time  5 hours  15 hours  Cumulative Amount of PPA-HCl (µg/cm 2 )  PPA-5  152.8  359.5  PPA-6  68.0  222.7  PPA-7  81.1  400.8  PPA-8  144.8  631.2  Time  19 hours  24 hours  Cumulative Amount orPPA-HCl (µg/cm 2 )  PPA-5  442.7  545.1  PPA-6  295.7  410.4  PPA-7  551.5  705.6  PPA-8  864.3  1147.5  Component Weight and Weight Percent Based on Total Solution Weight  PPA-9  PPA-10  PPA-11  PPA-12  g(wt%)  g(wt%)  g(wt%)  g(wt%)  PPA-HCl  0.5 (6.6)  0.5 (6.1)  0.5 (6.1)  0.5 (6.1)  K 3 PO$_{4 }$ 0  0.57 (7.0)  0.6 (7.3)  0.66 (8.0)  DI water  1.0 (13.2)  1.0 (12.2)  1.0 (12.2)  1.0 (12.1)  PG  0.5 (6.6)  0.5 (6.1)  0.5 (6.1)  0.5 (6.1)  Methyl alcohol  0.5 (6.6)  0.5 (6.1)  0.5 (6.1)  0.5 (6.1)  PIB adhesive  4 (52.6)  4 (49.0)  4 (48.8)  4 (48.4)  (30% solid)  HPMC  0.1 (1.3)  0.1 (1.2)  0.1 (1.2)  0.1 (1.2)  Heptane  (13.2)  (12.2)  (12.2)  (12.1) 