Aug. 30, 2012  41  US 2012/0220962 Al  TABLE 73  TABLE 70  TABLE 71  TABLE 74  TABLE 72  TABLE 75  [  0414]  Since the reaction between risperidone and N aO H is  not expected to be significant, the concentration ofNaOH in  the system is assumed to be independent from the amount of  risperidone added. Therefore, the NaOH concentration listed  in Table 71 equals the excess Na OH concentration, defined as  described in Example 2.  [0415]  The pH of the patches was measured as described in  the Methods section, but using a 2.4 cm 2  cm circular patch.  The pH of the risperidone patch measured increased from  7.98 to 10.15 when the calculated excess NaOH concentra› tion in the dried patch was increased from 0% to 1. 7%.  [0416]  The in vitro permeation of risperidone 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solution, 5% ethanol/  95% PBS buffer (0.05 M KH$_{2}$PO$_{4 }$ with 0.15 M NaCl, pH  adjusted to 6.5), was completely withdrawn and replaced with  fresh receiver solution at each time point.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 ofrisperi› done in the receiver solution. The cumulative amount of ris› peridone across human cadaver skin was calculated using the  measured risperidone concentrations in the receiver solu› tions.  [0417]  The cumulative amount of risperidone across  human cadaver skin at 24 hours increased from  O  .009 mg/ cm  2  to 0.312 mg/cm $^{2 }$when the calculated excess NaOH concen› tration in the dried patch was increased from 0% to 1.7%.  [0418]  The formulation ofRispe-2 provided up to 15-fold  more risperidone flux than in the absence ofNaOH (Rispe-1 ).  The highest pH formulation evaluated, Rispe-3, provided up  to 35-fold more flux than in the absence ofNaOH.  [0419]  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.  [0420]  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 /16 inch.  [0421]  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.  [0422]  Since paroxetine HCl 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  Risperidone  Benzyl Alcohol  Tetraglycol  PIB adhesive  (30% solid)  NaOH  DI water  Component Weight and Weight Percent  Based on Total Solution Weight  Rispe-1  Rispe-2  g(wt%)  g(wt%)  0.30 (3.4)  0.30 (3.3)  0.40 (4.5)  0.40 (4.5)  1.20 (13.5)  1.20 (13.4)  7.00 (78.7)  7.00 (78.0)  0  0.04 (0.4)  0  0.04 (0.4)  Rispe-3  g(wt%)  0.30 (3.3)  0.40 (4.4)  1.20 (13.3)  7.00 (77.4)  0.07 (0.8)  0.07 (0.8)  Risperidone  Benzyl Alcohol  Tetraglycol  PIB adhesive  NaOH  Component Weight and Weight Percent  Based on Dried Film Weight  Rispe-1  Rispe-2  g(wt%)  g(wt%)  0.30 (7.5)  0.30 (7.4)  0.40 (10.0)  0.40 (9.9)  1.20 (30.0)  1.20 (29.7)  2.10 (52.5)  2.10 (52.0)  0  0.04 (0.9)  Rispe-3  g(wt%)  0.30 (7.4)  0.40 (9.8)  1.20 (29.5)  2.10 (51.6)  0.07  (1.7)  Excess NaOH Concentration (wt%) and pH  Rispe-1  Rispe-2  Rispe-3  ExcessNaOH  0  0.9%  1.7%  Concentration  pH  7.98  8.79  10.15  Cumulative Amount of Risperidone (mg/cm 2 )  Time  5 hours  17.75 hours  24 hours  Rispe-1  0  0.004  0.009  Rispe-2  0.024  0.092  0.132  Rispe-3  0.092  0.264  0.312  Component Weight and Weight Percent  Based on Total Solution Weight  Pax-1  Pax-2  g(wt%)  g(wt%)  Paroxetine HCl  0.30 (5.1)  0.30 (5.0)  DI Water  0.30 (5.1)  0.35 (5.8)  THF  0.20 (3.4)  0.20 (3.3)  NaOH  0  0.05 (0.8)  Benzyl Alcohol  0.30 (5.1)  0.30 (5.0)  Glycerin  0.30 (5.1)  0.30 (5.0)  PIB adhesive  4.00 (67.8)  4.00 (66.7)  (30% solid)  n-Heptane  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)  Weight and Theoretical Weight Percent  Based on Dried Film Weight  Pax-1  Pax-2  g(wt%)  g(wt%)  Paroxetine HCl  0.30 (14.3)  0.30 (14.0)  NaOH  0  0.05 (2.3)  Benzyl Alcohol  0.30 (14.3)  0.30 (14.0)  Glycerin  0.30 (14.3)  0.30 (14.0)  PIB adhesive  1.20 (57.1)  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)  Example 22 