Nov. 4, 2004  43  US 2004/0220262 Al  [0429]  The formulation of Rispe-2 provided up to 15-fold  more risperidone flux than in the absence of NaOH (Rispe- 1). The highest pH formulation evaluated, Rispe-3, provided  up to 35-fold more flux than in the absence of NaOH.  [0430]  An in vitro skin permeation study was conducted  using three paroxetine hydrochloride transdermal systems,  designated Pax-1, Pax-2 and Pax-3, the compositions of  which are set forth in Table 74.  [0431]  Round disc samples were prepared in a manner  similar to that described in the Methods section, except that  the formulation was dried at a temperature of 65°  C. and the  discs were cut into discs having a diameter of  9 /26 inch.  [0432]  The theoretical percent weight for each ingredient  after drying ( calculated assuming all volatile ingredients  were completely removed during drying) is set forth in Table  75.  [0434]  Since paroxetine HCl is an acid addition salt of a  free base, it reacts with NaOH. The concentration of NaOH  in the system after the reaction is completed depends on the  amount of paroxetine HCl added. The remaining NaOH  concentration after the reaction is completed is defined as  the excess NaOH concentration, and was calculated as  described in Example 2. The pH was measured as described  in the Methods section but using a 2.4 cm 2  circular patch.  The pH of the paroxetine HCl patch increased from 9.32 to  10.62 when the calculated excess NaOH concentration in the  dried patch was increased from 0.8% to 3.1 %. The pH of the  patch without NaOH was 7.37.  [0435]  The in vitro permeation of paroxetine HCl through  human cadaver skin from these discs was measured as  described in the Methods section. Three diffusion cells were  used for each formulation. The receiver solution, 5% N-me› thylpyrrolidone/95% water, was completely withdrawn and  replaced with fresh receiver solution at each time point. The  samples taken were analyzed by an  HPLC  for the concen› tration of paroxetine HCl in the receiver solution. The  cumulative amount of paroxetine HCl that permeated across  the human cadaver skin was calculated using the measured  paroxetine HCl concentrations in the receiver solutions.  [0436]  The cumulative amount of paroxetine HCl across  human cadaver skin at 24 hours increased from 0.247  mg/cm $^{2 }$to 0.850 mg/cm$^{2 }$when the calculated excess NaOH  concentration in the dried patch was increased from 0.8% to  3.1 % as compared to 0.133 mg/cm 2  for the formulation  without NaOH.  [0437]  The formulation of Pax-2 provided up to 2-fold  more paroxetine HCl flux than in the absence of NaOH  (Pax-1). The highest pH formulation evaluated, Pax-3, pro› vided up to 6-fold more flux than in the absence of NaOH.  [0438]  An in vitro skin permeation study was conducted  using three galanthamine hydrobromide transdermal sys› tems, designated Gala-1, Gala-2 and Gala-3, the composi› tions of which are set forth in Table 78.  [0439]  Round disc samples were prepared in a manner  similar to that described in the Methods section, except that  the formulation was dried at a temperature of 65°  C. and the  discs were cut into discs having a diameter of  9 /26 inch.  [0440]  The theoretical percent weight for each ingredient  after drying ( calculated assuming all volatile ingredients  were completely removed during drying) is set forth in Table  79.  Example 23  Example 22  TABLE 76  TABLE  74  TABLE 77  TABLE  75  [0433]  Excess NaOH Concentration (wt %) and pH  Excess NaOH  Concentration  pH  Pax-1  7.37  Pax-2  0.8%  9.32  Pax-3  3.1%  10.62  Paroxetine HCl  DI Water  THF  NaOH  Benzyl Alcohol  Glycerin  PIE adhesive  (30% solid)  n-Heptane  Component Weight and Weight Percent  Based on Total Solution Weight  Pax-1  Pax-2  g(wt%)  g(wt%)  0.30 (5.1)  0.30 (5.0)  0.30 (5.1)  0.35 (5.8)  0.20 (3.4)  0.20 (3.3)  0  0.05 (0.8)  0.30 (5.1)  0.30 (5.0)  0.30 (5.1)  0.30 (5.0)  4.00 (67.8)  4.00 (66.7)  0.50 (8.5)  0.50 (8.3)  Pax-3  g(wt%)  0.30 (4.9)  0.40 (6.6)  0.20 (3.3)  0.10 (1.6)  0.30 (4.9)  0.30 (4.9)  4.00 (65.6)  0.50 (8.2)  Cumulative Amount of paroxetine HCl (mg/cm 2 )  Time  4.75 hours  17.75 hours  24 hours  Pax-1  0.014  0.082  0.133  Pax-2  0.008  0.141  0.247  Pax-3  0.145  0.616  0.850  Paroxetine HCl  NaOH  Benzyl Alcohol  Glycerin  PIE adhesive  Weight and Theoretical Weight Percent  Based on Dried Film Weight  Pax-1  g(wt%)  0.30 (14.3)  0  0.30 (14.3)  0.30 (14.3)  1.20 (57.1)  Pax-2  g(wt%)  0.30 (14.0)  0.05 (2.3)  0.30 (14.0)  0.30 (14.0)  1.20 (55.8)  Pax-3  g(wt%)  0.30 (13.6)  0.10 (4.5)  0.30 (13.6)  0.30 (13.6)  1.20 (54.5) 