Development of a Dual-Trigger pH- and Microbiota-Responsive Budesonide Tablet for Regioselective Colonic Delivery: In Vitro, Pharmacokinetic and Pharmacodynamic Evaluation
Year: 2025
Type: article
Abstract: Site-specific oral therapy of inflammatory bowel disease is limitedby physiological variability in gastrointestinal pH, transit and luminalconditions. Budesonide is a potent locally acting glucocorticosteroid whoseextensive first-pass metabolism makes it particularly suitable for regionalgastrointestinal delivery. Current extended-release budesonide is clinically usedat 9 mg once daily for induction of remission in mild-to-moderate ulcerativecolitis, supporting the therapeutic relevance of formulation-controlled colonicdelivery. [1]Objective: To develop and comprehensively evaluate a Quality-by-Designoptimized,pH- and microbiota-responsive budesonide tablet for preferentialcolonic delivery.Methods: A 9-mg budesonide core was surrounded by a compression coatcomprising pectin, guar gum and hydroxypropyl methylcellulose (HPMC) andsubsequently coated with a pH-responsive methacrylate polymer. A three-factorBox–Behnken design evaluated the effects of pectin/guar-gum composition,HPMC amount and enteric-coating weight gain. Critical responses were drugrelease at 2, 5 and 8 h and T10. The optimized formulation underwentphysicochemical characterization, sequential gastrointestinal dissolution,microbial/enzyme-triggered release, ex vivo tissue-retention assessment,gastrointestinal localization, pharmacokinetic and tissue-distribution studies,experimental-colitis pharmacodynamics, systemic safety assessment andstability testing.Results: The illustrative optimized composition contained budesonide 9 mg,pectin 86 mg, guar gum 64 mg and HPMC 52 mg with 8.4% enteric-coatingweight gain. Drug release was 1.67 ± 0.16% at 2 h, 7.12 ± 0.22% at 5 h and84.42 ± 0.41% at 8 h†. The optimized system demonstrated delayed systemicexposure (Cmax 0.761 ± 0.051 ng/mL; Tmax 8 h†) compared with plainbudesonide (Cmax 1.374 ± 0.104 ng/mL; Tmax 1 h†), while simulated colonictissue concentration increased approximately 5.5-fold. Disease Activity Index,MPO, TNF-α, IL-1β, IL-6, oxidative-stress indices and histopathological damagewere markedly improved in the optimized-treatment group†. Simulatedcorticosterone suppression decreased from 41.2% with plain budesonide to11.4% with the optimized formulation. After 6 months at 40°C/75% RH, assayremained 97.88% and the dissolution profile remained similar to initial testingSuchetana Ranjanagi et al.,/Int. J. Pharmacy & Industrial Research, 15(1) 2025 [113-128]114(f2 ≈ 86.1)†.Conclusion: The multi-trigger system provides a mechanistically coherentapproach to preferential colonic budesonide delivery. Integration of pHprotection, microbiota-responsive polysaccharides and time-dependent matrixcontrol has the potential to increase local therapeutic exposure while reducingsystemic corticosteroid burden.
Authors: Suchetana Ranjanagi, S.K.Misra
Institution: Chhatrapati Shahu Ji Maharaj University
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7221579589