Development of Enteric-Coated Resveratrol-Loaded Eudragit S-100 Microparticles for Targeted Colonic Delivery in Colitis Management with Qbd Approach

Abstract

This study aimed to develop and optimize resveratrol-loaded microparticles for targeted delivery in colitis  using a Quality by Design (QbD) approach. Microparticles were prepared by using the emulsification–solvent evaporation method, with critical process parameters and material attributes systematically varied according to a Box–Behnken design. Among 17 formulations, the optimized batch was obtained at X₁ = 5.268% tristearin concentration, X₂ = 975 rpm stirring speed, and X₃ = 2.51% PVA concentration, followed by Eudragit S-100 coating to achieve pH-responsive release. The optimized formulation demonstrated uniform spherical microparticles with desirable particle size distribution, entrapment efficiency above 85%, and reproducible drug content. In-vitro release studies confirmed negligible drug release under gastric and intestinal pH, with sustained release at colonic pH, validating the suitability of the coating strategy. Entrapment efficiency was calculated indirectly by quantifying unentrapped drug in the supernatant after centrifugation and dilution in solvent, ensuring complete solubilization before analysis. Microparticles equivalent to 50 mg of resveratrol (≈ 590 mg microparticles) were used for dissolution studies to maintain dose uniformity across all formulations. Cytotoxicity studies in Caco-2 cells using the MTT assay showed that PRS, RUMP, and RCMP maintained >90% viability across 5–100 µM concentrations, with no significant trend observed (p > 0.05); minor fluctuations were attributed to normal assay variability. As per the resultfinding, the study established a robust QbD-optimized microparticle system capable of delivering resveratrol efficiently to the colon, highlighting its therapeutic potential for colitis management. The developed system presents a viable approach to resveratrol delivery that targets the colon in the management ofcolitis.