Quality By Design Driven Development of Enteric-Coated Resveratrol Micropellets For Colitis Management

Abstract

Background:
Ulcerative colitis (UC) is a chronic condition requiring targeted drug delivery for effective management. Resveratrol, with its anti-inflammatory properties, faces bioavailability challenges in the colon. This study focuses on formulating resveratrol-loaded micropellets for targeted colonic delivery using Eudragit S-100 and an HPMC as enteric coating polymer.
Aim:
The study aimed to develop and optimize resveratrol-loaded micropellets using Quality by Design (QbD) principles to ensure controlled release in the colon and assess their physicochemical and biological properties for UC management.
Method:
The micropellets were optimized using a Box-Behnken Design with three factors at three levels and were formulated via the ionotropic gelation method. Their stability and morphology were confirmed through characterization techniques such as FTIR, SEM, DSC, and XRD. Micrometric properties, including the angle of repose, bulk density, and compressibility index, were assessed. Biological evaluations involved cell viability assays, ROS generation studies, cytokine profiling using CBA, and NF-kB expression analysis. The drug release profile was examined under different pH conditions to mimic the colonic environment, and stability studies were also performed.
Result:
The optimized micropellets formulation exhibited several key characteristics, including a particle size of 552 ± 7.42 µm, an entrapment efficiency of 86.97 ± 0.34%, and a drug release of 96.14 ± 4.38% over 16 hours, with negligible drug release occurring in the stomach. The formulation demonstrated excellent flow properties, with an angle of repose of 24.271° ± 0.417, a bulk density of 0.783 ± 0.006 (g/cm3), and a tapped density of 0.785 ± 0.019 (g/cm3). Stability testing confirmed the preservation of resveratrol within the micropellets. Biological assessments revealed significant anti-inflammatory activity, coated micropellets reducing colon inflammation, as indicated by a drop in MFI values to 8736. Controlled release, particularly from HPMC-coated micropellets, was successfully achieved in colonic conditions.
Conclusion:
HPMC coated Resveratrol-loaded micropellets offer a promising approach for targeted
Management, providing controlled drug release, reduced inflammation, and potential for improved therapeutic outcomes.