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Objective: In this study, a Box-Behnken design (BBD) of response surface method was used to investigate and optimize the process parameters of Repaglinide. Repaglinide is a suitable candidate for iontophoretic delivery due to its first pass metabolism and frequent dosing, hence transdermal delivery was required to improve bioavailability and patient compliance. The goal was to identify the optimum levels of independent variables intended for the dependent variable. Materials and Method: Independent variables selected were current intensity (X 1 ), medium/pH (X 2 ), polymer (HPMC) concentration (X 3 ). The dependent variables studied were amount of drug permeated in 4 h (Y 1 : Q 4 ), 24 h (Y 2 : Q 24 ) and lag time (Y 3 ). The BBD provided an excellent relationship between the independent and dependent variables. Mathematical equations, response surface and contour plots were used to show the interactions and discuss the results in graphic model. Results: The regression equation generated for the iontophoretic permeation was Y 1 = 898.68 + 114.51X 1 + 325.29X 2 - 0.83X 3 +142.62X 1 X 2 – 27.03X 1 X 3 –47.84X 2 X 3 -8.85X 1 2 - 90.26X 2 2–302.09X 3 2; Y(2) = +3446.82+275.42 X 1 +1092.93 X 2 +37.23 X 3 +136.49 X 1 X 2 -114.52 X 1 X 3 -241.01 X 2 X 3 -164.78 X 1 2 -487.25 X 2 2 -990.88 X 3 2 . The results of statistics between factorial and theoretical profiles were used to select optimized critical process parameters. Conclusion: Thus, it was concluded that optimal use of amount of polymer and current intensity in the permeation of drug could increase the bioavailability and the interactions can be defined as a regression model which is statistically significant. Key words: Box-Behnken, Factorial design, Iontophoresis, Optimization, Repaglinide, Transdermal.

Use of Box-Behnken Experimental design for Optimization of process Variables in Iontophoretic delivery of Repaglinide