Aug. 6, 2009  38  US 2009/0197849 Al  1 ). The highest pH formulation evaluated, Pax-3, provided up  to 6-fold more flux than in the absence ofNaOH.  [0410]  An  in vitro skin permeation study was conducted  using three galanthamine hydrobromide transdermal sys› tems, designated Gala-I, Gala-2 and Gala-3, the composi› tions of which are set forth in Table 78.  [0411]  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  of9/26  inch.  [0412]  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.  [0414]  The in vitro permeation of galanthamine HBr  through human cadaver skin from these discs was measured  as described in the Methods. Three diffusion cells were used  for each formulation. The receiver solution, 5% ethanol/95%  PBS buffer (0.05 M KH$_{2}$PO$_{4 }$ with0.15 MNaCl, pH adjusted  to 6.5), was completely withdrawn and replaced with fresh  receiver solution at each time point. The samples taken were  analyzed by an HPLC for the concentration galanthamine  HBr in the receiver solution. The cumulative amount of gal› anthamine HBr that permeated across the human cadaver skin  was calculated using the measured galanthamine HBr con› centrations in the receiver solutions.  [0415]  The cumulative amount of galanthamine HBr across  human cadaver skin at 24 hours increased from 1.254 mg/cm 2  to 1.750 mg/cm $^{2 }$when the calculated excess NaOH concen› tration in the dried patch was increased from 0% to 1.0% as  compared to 0.624 mg/cm 2  for the formulation without  NaOH.  [0416]  The formulation of Gala-2 provided up to 2-fold  more galanthamine HBr flux than in the absence of NaOH  (Gala-I). The highest pH formulation evaluated, Gala-3, pro› vided up to 3-fold more flux than in the absence ofNaOH.  [0417]  An  in vitro skin permeation study was conducted  using three hydromorphone hydrochloride transdermal sys› tems, designated Hymo-1, Hymo-2 and Hymo-3, the compo› sitions of which are set forth in Table 82.  [0418]  Round disc samples were prepared as 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 /16 inch.  [0419]  The theoretical percent weight for each ingredient  after drying ( calculated assuming all volatile ingredients  were completely removed during drying) is set forth in Table  83.  [0413]  Since galanthamine HBr is an acid addition salt of a  free base, it reacts with NaOH. The concentration ofNaOH in  the system after the reaction is completed depends on the  amount of galanthamine HBr 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 galanthamine HBr patch increased from 8.73 to 10.56  when the calculated excess NaOH concentration in the dried  patch was increased from 0% to 1.0%. The pH of the formu› lation without NaOH was 6.53.  TABLE 82  TABLE 80  TABLE 79  TABLE 78  TABLE 81  Example 24  Component Weight and Weight Percent Based on Total Solution  Wei  t  Gala-!  Gala-2  Gala-3  g(wt%)  g(wt%)  g(wt%)  Galanthamine  0.40 (4.7)  0.40 (4.6)  0.40 (4.6)  HBr  DI Water  0.30 (3.5)  0.34 (3.9)  0.38 (4.3)  NaOH  0  0.04 (0.5)  0.08 (0.9)  Glycerin  1.00 (11.6)  1.00 (11.5)  1.00 (11.4)  Benzyl Alcohol  0.40 (4.7)  0.40 (4.6)  0.40 (4.6)  PIB adhesive  6.00 (69.8)  6.00 (69.1)  6.00 (68.5)  (30% solid)  n-Heptane  0.50 (5.8)  0.50 (5.8)  0.50 (5.7)  Weight and Theoretical Weight Percent Based on Dried Film Weight  Gala-!  Gala-2  Gala-3  g(wt%)  g(wt%)  g(wt%)  Galanthamine HBr  0.40 (11.1)  0.40 (11.0)  0.40 (10.9)  NaOH  0  0.04 (1.1)  0.08 (2.2)  Glycerin  1.00 (27.8)  1.00 (27.5)  1.00 (27.2)  Benzyl Alcohol  0.40 (11.1)  0.40 (11.0)  0.40 (10.9)  PIB adhesive  1.80 (50.0)  1.80 (49.5)  1.80 (48.9)  Excess NaOH Concentration (wt%) and pH  ExcessNaOH  Concentration  pH  Gala-!  6.53  Gala-2  0%  8.73  Gala-3  1.0%  10.56  Component Weight and Weight Percent Based  on Total Solution Weight  Hymo-1  Hymo-2  g(wt%)  g(wt%)  Hydromorphone HCl  0.20 (2.8)  0.20 (2.7)  DI Water  0.30 (4.1)  0.38 (5.1)  NaOH  0  0.08 (1.0)  Glycerin  1.25 (17.2)  1.25 (16.9)  PIB adhesive  5.00 (69.0)  5.00 (67.6)  (30% solid)  n-Heptane  0.50 (6.9)  0.50 (6.8)  Hymo-3  g(wt%)  0.20 (2.7)  0.43 (5.7)  0.13 (1.7)  1.25 (16. 7)  4.00 (66.7)  0.50 (6.7)  Cumulative Amount of Galanthamine HBr (mg/cm 2 )  Time  6 hours  18 hours  24 hours  Gala-!  0.140  0.429  0.624  Gala-2  0.480  1.058  1.254  Gala-3  0.475  1.412  1.750  Example 23 