APPLICATION OF THE BEHNKEN DESIGN BOX TO OPTIMIZE THE PRODUCTION OF DEXIBUPROFEN NANOCRYSTALS USING THE TOP-DOWN METHOD
Background: Dexibuprofen (DXI) is the S (+) enantiomer form of Ibuprofen [(±)-α-methyl-4-(2-methylpropyl) benzeneacetic acid]. DXI exhibits poor physical solubility, measuring less than 1 mg/mL, which results in low bioavailability in the gastrointestinal tract. One approach to enhance the solubility of DXI involves reducing its particle size to form nanocrystals. Objective: This study aims at synthesizing stable dexibuprofen (DXI) nanocrystals using the top-down method. Additionally, it aims to optimize the synthesis process using the Box-Behnken method. Method: The study aims to optimize the concentrations of DXI (50-150 mg), PVP K90 (1-3%), and Decyl Glucoside (DG) (1-3%) to achieve optimal conditions to produce DXI nanocrystals using the top-down method. Furthermore, the study aims to develop a mathematical model for the preparation of DXI nanocrystals, considering the concentrations of DXI, PVP K90, and Tween 80. The optimization of DXI nanocrystal production conditions employs the Response Surface Method, specifically the Box-Behnken Design, with three factors and three levels. Results: Within the framework of the Box-Behnken design, this study encompassed a total of 15 trials. The analysis outcomes revealed that the optimal concentration for DXI in the production of DXI nanocrystals was determined to be 150 mg, while the optimal concentrations for PVP K90 and DG were found to be 1% each. The Response Surface Regression analysis yielded a constant value of 1.22. Consequently, an equation was derived as follows: Y = 1.22 - 0.654DXI + 5.338PVPK90 + 1.400DG. Conclusion: The optimized DXI nanocrystals were successfully synthesized using an anti-solvent deposition method, incorporating the condition optimization results obtained from the Box-Behnken design.