Development and In Vitro Evaluation of a pH-Responsive Hydrogel for Colon-Targeted Delivery of a Glucocorticoid
Abstract
Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, requires effective local drug delivery to the colon while minimizing systemic corticosteroid exposure. Budesonide is a potent glucocorticoid with high local anti-inflammatory activity; however, its poor aqueous solubility and limited site-specific delivery present formulation challenges. The present study aimed to develop and optimize a Budesonide-loaded pH-responsive hydrogel for colon-targeted drug delivery. Preformulation studies included organoleptic evaluation, melting point determination, solubility analysis, UV spectrophotometric characterization, and compatibility assessment. Budesonide appeared as a white to off-white crystalline powder with a melting point of 225 ± 1.00 °C and exhibited poor aqueous solubility. The UV method showed λmax at 246 nm with excellent linearity (R² = 0.9991). FTIR and DSC analyses confirmed compatibility between Budesonide and selected excipients. Formulation optimization was carried out using a Box–Behnken Design employing polymer concentration, neutralizer percentage, and crosslinking density as independent variables. The optimized formulation (Run 10) contained 1.5% w/w polymer, 1.5% w/w neutralizer, and 0.2% w/w crosslinker, exhibiting viscosity of 4980 cP, pH 7.12, drug content of 91.6%, spreadability of 23.5 cm/g, and drug release of 90.2%. The hydrogel was homogeneous, stable, and demonstrated high entrapment efficiency (91.4%) and gel fraction (87.5%). Swelling studies confirmed pronounced pH-responsive behavior, with maximum swelling at pH 7.4. In-vitro release studies showed minimal drug release in acidic conditions and sustained release at colonic pH. The formulation followed Korsmeyer– Peppas kinetics, indicating anomalous transport. Stability studies confirmed satisfactory performance over six months, highlighting its potential for colon-targeted Budesonide delivery.