BOX-BEHNKEN DESIGN FOR DEVELOPMENT AND OPTIMIZATION OF ACETAZOLAMIDE MICROSPHERES

This study describes a Box-Behnken experimental design to optimize the formulation of Acetazolamide (ACZ) loaded microspheres by solvent evaporation method using Eudragit RS100 as a polymer. The prepared microspheres were evaluated for their production yields, particle size distribution, morphology, entrapment efficiency % and drug release characteristics. Box-Behnken design produced fifteen formulations containing specified amounts of the independent variables, drug: polymer ratio (X₁), surfactant concentration % (X₂) and stirring rate (rpm) (X₃), the dependent factors studied were entrapment efficiency % (Y₁), % drug released after 6 hrs (Y₂) and particle size (µm) (Y₃). Acetazolamide-loaded microspheres were spherical in shape and had a smooth surface. The results showed that the production yield of the prepared microspheres was found to be between 70.45 and 92.98%. The formulated microspheres exhibited acceptable entrapment efficiency % values in the range of 34.84 to 76.19%. The computer optimization process, surface and contour plots predicted the levels of independent variables X₁, X₂ and X₃ (1:5, 0.5 and 890, respectively), for maximized response of EE% (80.25%), controlled release of drug (39.11%) and optimized particle size (1043.05 µm). The Box-Behnken factorial design illustrated the role of the derived polynomial equations and surface plots in predicting the values of dependent variables for the formulation and optimization of acetazolamide microspheres. This study proved that Box-Behnken factorial design could efficiently be applied for modeling of acetazolamide microspheres.