DESIGN OF GASTRORETENTIVE POLYMERIC LOW-DENSITY MICROBALLOONS OF MEBENDAZOLE USING RESPONSE SURFACE METHODOLOGY

Abstract

Objective: The main objective of the present work is the development of polymeric low-density microballoons for prolonged gastroretentive delivery and optimization of promising formulation by central composite design of response surface methodology. Methods: Mebendazole-loaded microballoons were prepared by emulsion solvent diffusion method using Eudragit S-100 and hydroxypropyl methylcellulose as release controlling polymers. All the formulations of mebendazole-loaded microballoons showed buoyancy up to 8 h. Percentage of Eudragit S-100 (X1) in total amount of polymer and solvent ratio (X2) was taken as two independent variables. The responses are evaluated to study the effect of independent variables and the optimum formulation was chosen based on numerical and graphical optimization. Results: The optimized formulation MBZ9 was composed of 100 mg of mebendazole, 75% of Eudragit S-100, and 25% of HPMC with DCM: ETH ratio of 1:1. The optimized formulation showed yield (81%), buoyancy (86.4%), entrapment efficiency (82.01%), and cumulative drug release for 12 h (79.99%). The optimized formulation was characterized by differential scanning calorimetry, and Fourier-transform infrared spectroscopy. It followed mixed order and the mechanism of drug release was diffusion as per R2=0.905 in Higuchi model. Conclusion: Microballoons of mebendazole produced with 75% Eudragit S-100, X1 (750 mg), 25% of HPMC polymer, and 1:1 DCM: ETH solvent ratio X2 (10:10 ml) optimized by response surface methodology are successful with enhanced gastroretentive effect and controlled release to elicit promising anthelminthic effect in the gastrointestinal tract.