42  US 2003/0124176 Al  Jul. 3, 2003  [0453]  An in vitro skin permeation study was conducted  using three enalapril maleate transdermal systems, desig› nated Enal-1, Enal-2 and Enal-3, the compositions of which  are set forth in Table 90.  [0454]  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 /26 inch.  [0455]  The theoretical percent weight for each ingredient  after drying ( calculated assuming all volatile ingredients  were completely removed during drying) is set forth in Table  91.  [0457]  Since enalapril maleate 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 enalapril maleate 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  of each patch was measured  as described in the Methods section but using a 2.4 cm 2  circular patch. The  pH  of the enalapril maleate patch  increased from 7.29 to 10.82 when the calculated excess  NaOH concentration in the dried patch was increased from  1.9% to 6.9%. The  pH  of the patch without NaOH was 3.12.  [0458]  The in vitro permeation of enalapril maleate  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 The receiver solution, 10%  ethanol, was completely withdrawn and replaced with fresh  receiver solution at each time point. The samples taken were  analyzed by an  HPLC  for the concentration of enalapril  maleate in the receiver solution. The cumulative amount of  enalapril maleate that permeated across the human cadaver  skin was calculated using the measured enalapril maleate  concentrations in the receiver solutions.  [0459]  The cumulative amount of enalapril maleate across  human cadaver skin at 24 hours increased from 0.029  mg/cm $^{2 }$to 1.826 mg/cm $^{2 }$when the calculated excess NaOH  concentration in the dried patch was increased from 1.9% to  6.9% as compared to undetectable flux for the formulation  without NaOH. The formulation of Enal-3 provided up to  63-fold more enalapril maleate flux than the formulation of  Enal-2.  [0460]  All patents, publications, and other published  documents mentioned or referred to in this specification are  herein incorporated by reference in their entirety.  [0461]  It is to be understood that while the invention has  been described in conjunction with the preferred specific  embodiments hereof, the foregoing description, as well as  the examples which are intended to illustrate and not limit  the scope of the invention, it should be understood by those  skilled in the art that various changes may be made and  equivalents may be substituted without departing from the  scope of the invention. Other aspects, advantages and modi› fications will be apparent to those skilled in the art to which  the invention pertains.  [0462]  Accordingly, the scope of the invention should  therefore be determined with reference to the appended  claims, along with the full range of equivalents to which  those claims are entitled.  We claim:  1.  A  method for enhancing the flux of an analgesic agent  through a body surface, comprising:  ( a) administering the analgesic agent to a localized region  of a human patient’s body surface; and  TABLE  93  TABLE  90  TABLE  92  TABLE  91  Example 26  Component Weight and Weight Percent Based on Total Solution  Weight  Enal-1  Enal-2  Enal-3  g(wt%)  g(wt%)  g(wt%)  Enalapril Maleate  0.50 (8.8)  0.50 (8.4)  0.50 (8.1)  PG  0.50 (8.8)  0.50 (8.4)  0.50 (8.1)  DI Water  0.20 (3.5)  0.33 (5.5)  0.45 (7.3)  NaOH  0  0.13 (2.1)  0.25 (4.0)  PIE adhesive  4.00 (70.2)  4.00 (67.2)  4.00 (64.5)  (30% solid)  n-Heptane  0.50 (8.8)  0.50 (8.4)  0.50 (8.1)  Weight and Theoretical Weight Percent Based on Dried Film Weight  Enal-1  Enal-2  Enal-3  g(wt%)  g(wt%)  g(wt%)  Enalapril Maleate  0.50 (22.7)  0.50 (21.5)  0.50 (20.4)  PG  0.50 (22.7)  0.50 (21.5)  0.50 (20.4)  NaOH  0  0.13 (5.4)  0.25 (10.2)  PIE adhesive  1.20 (54.5)  1.20 (51.6)  1.20 (49.0)  [0456]  Cumulative Amount of Enalapril Maleate (mg/cm 2 )  Time  5.25 hours  17.25 hours  23.75 hours  Enal-1  0  0  0  Enal-2  0.021  0.029  0.029  Enal-3  1.027  1.640  1.826  Excess NaOH Concentration  (wt  %) and pH  Excess NaOH  Concentration  pH  Ena!- 1  3.12  Enal-2  1.9%  7.29  Enal-3  6.9%  10.82 