QbD aided optimization and molecular docking of pH-sensitive hydrogels for targeted colon delivery in ulcerative...

Oral formulations of aminosalicylates are widely used in the treatment of ulcerative colitis (UC), but their efficacy is limited by low absorption and bioavailability due to first-pass metabolism and gastric degradation. pH-sensitive hydrogels were formulated for colon-targeted, delayed drug release to address this concern. Moreover, molecular docking was conducted to evaluate the binding affinity between β-cyclodextrin (oligomer) and balsalazide disodium. 15 formulations were developed using a Box-Behnken design in Design-Expert® 11, varying the concentrations of cross-linker, oligomer, and monomer while keeping the initiator constant. Hydrogels were developed via free radical polymerization using N,N-methylene bisacrylamide (MBA), β-cyclodextrin, potassium persulfate (KPS), and acrylic acid. Formulations were evaluated for swelling behavior, drug release, entrapment efficiency, porosity, and sol-gel fraction. The hydrogels exhibited maximum swelling at pH 7.2 (3783.4%) and a low sol fraction (10%), achieving 96% drug entrapment. FTIR suggested no interaction between the drug and excipients used. DSC and SEM analyses revealed stable thermal behavior and porous morphology. Molecular docking confirmed promising binding between balsalazide disodium and β-cyclodextrin. In vitro release studies showed sustained drug release for up to 8 hours, with kinetic modeling best fitting the Hixson-Crowell model, indicating drug release by change in geometry, surface area, and swelling of the hydrogel matrix. In the current research work, the optimized pH-sensitive hydrogel providing an effective sustained-release system for balsalazide disodium has been successfully developed, exhibiting promising pH-responsive drug-release characteristics.