Jun.5,2003  27  US 2003/0104041 Al  tion. Normal saline was used as the receiver solution. The  entire receiver solution was collected and replaced with  fresh saline at each time point. The receiver solution col› lected was analyzed by an  HPLC  for the concentration of  ibuprofen. The cumulative amount of ibuprofen across  human cadaver skin was calculated using the measured  ibuprofen concentrations in the receiver solutions, which  were plotted versus time and are described below.  [0309]  The cumulative amount of ibuprofen across human  cadaver skin at 24 hours increased from 0.33 mg/cm $^{2 }$to 5.74  mg/cm $^{2 }$when the calculated excess NaOH concentration in  the gel was increased from 0% to 1.74% (Ibu-4), i.e., up to  about 17-fold more flux was obtained than with the formu› lation having 0% excess NaOH concentration. The cumu› lative amount of ibuprofen that permeated across the human  cadaver skin at 24 hours from the formulation with an excess  NaOH concentration of0.98% (Ibu-3, 1.12 mg/cm 2 )  is about  3 times higher than that from the formulation with an excess  NaOH concentration of 0% (Ibu-2, 0.33 mg/cm 2 ).  [0312]  Since PPA-HCl is a salt of a free base, it reacts with  Na$_{2}$CO$_{3}$ .  The concentration of Na$_{2}$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$_{3 }$ concentration," which is defined by the following equation.  [0313]  The excess Na$_{2}$ CO$_{3 }$ for these four PPA-HCl sys› tems 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$_{3 }$ concentration in the dried patch was increased from  0.4% to 16.7%.  [Na2C03 excessJ=[Na2C03 tota1J-[Na2C03 needed for neu› tralization]  [0310]  An in vitro skin permeation study was conducted  using four phenylpropanolamine hydrochloride transdermal  systems, designated PPA-5, PPA-6, PPA-7, and PPA-8, the  compositions of which are set forth in Table 15. The matrix  patches were prepared and evaluated using the same proce› dures 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 16.  [0314]  The cumulative amount of PPA-HCl across human  cadaver skin was calculated using the measured  PPA-HCl  concentrations in the receiver solutions.  TABLE  15  TABLE 17  TABLE  16  Example 6  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  Component Weight and Weight Percent Based on Total Solution Weight  PPA-5  PPA-6  PPA-7  PPA-8  g (wt%)  g(wt%)  g(wt%)  g(wt%)  PPA-HCl  0.5 (6.7)  0.5 (5.7)  0.5 (5.6)  0.5 (5.5)  Na$_{2}$CO$_{3 }$ 0  0.29 (3.3)  0.44 (5.0)  0.74 (8.1)  DI water  1.0 (13.5)  2.0 (23.0)  2.0 (22.6)  2.0 (21.9)  Methyl alcohol  0.5 (6.7)  0.5 (5.7)  0.5 (5.6)  0.5 (5.5)  PG  0.2 (2.7)  0.2 (2.3)  0.2 (2.3)  0.2 (2.2)  HPMC  0.01 (0.1)  0.01 (0.1)  0.01 (0.1)  0.01 (0.1)  Heptane  1.2 (16.2)  1.2 (13.8)  1.2 (13.6)  1.2 (13.1)  PIE adhesive  4 (54.0)  4 (46.0)  4 (45.2)  4 (45.2)  (30% solid)  Weight and Theoretical Weight Percent Based on Dried Film Weight  PPA-5  PPA-6  PPA-7  PPA-8  g(wt%)  g(wt%)  g(wt%)  g(wt%)  PPA-HCl  0.5 (26.2)  0.5 (22.7)  0.5 (21.3)  0.5 (18.9)  Na$_{2}$CO$_{3 }$ 0  0.29 (13.2)  0.44 (18.7)  0.74 (27.9)  PG  0.2 (10.5)  0.2 (9.1)  0.2 (8.5)  0.2 (7.5)  HPMC  0.01 (0.5)  0.01 (0.5)  0.01 (0.4)  0.01 (0.4)  PIE adhesive  1.2 (62.8)  1.2 (54.5)  1.2 (51.1)  1.2 (45.3)  (30% solid)  [0311] 