OPTIMIZING PRONIOSOMES FOR CONTROLLED RELEASE OF KETOPROFEN USING BOX-BEHNKEN EXPERIMENTAL DESIGN

The present study deals with the investigation of the effect of formulation variable on ketoprofen (KP) proniosomes prepared by spray method. A three factor, three level Box-Behnken design (DOE) with response surface methodology (RSM) was run to evaluate the main and interaction effect of several independent formulation variables that included cholesterol concentration % (X₁), total lipid concentration  µmole (X₂), and total amount of drug mg (X₃). The dependent variable included entrapment efficiency EE% (Y₁) and % drug released at 6 hrs (Y₂). A desirability function was used to maximize EE% and minimize the release percent to attain a controlled release formula. The transformed values of the independent variables and the dependent variables were subjected to multiple regressions to establish a full-model second-order polynomial equation. Contour plots were constructed to show the effects of X₁, X₂ and X₃ on the Y₁ and Y₂. The computer optimization process and contour plots predicted the levels of independent variables X₁, X₂, and X₃ (30, 2000, and 75 respectively), for maximized response of EE% (82.77%) and controlled release of drug (40.65%). The Box-Behnken design demonstrated the role of the derived equation and contour plots in predicting the values of dependent variables for the preparation and optimization of ketoprofen proniosomes. This study proved that Box-Behnken design could efficiently be applied for modeling of ketoprofen proniosomes.