A pH/Enzyme Dual-Responsive Dropping Pill System for Colon-Targeted Delivery of Naringin

Ulcerative colitis requires targeted therapy to enhance efficacy and minimize systemic side effects. This study aimed to address the low bioavailability and nonspecific release of naringin, a natural anti-inflammatory flavonoid, by developing a colon-targeted delivery system for ulcerative colitis treatment.

The pill core was prepared via a melt-dropping method and optimized using orthogonal experimental design. The pH/enzyme dual-responsive coating was refined using Box-Behnken response surface methodology. In vitro release was evaluated in a gradient pH model (gastric pH 1.2, intestinal pH 6.8, colonic pH 7.6) with enzymatic tolerance tests.

The optimal core conditions were a drug-to-matrix ratio of 1:3, melting temperature of 90°C, and condensation temperature of 5°C, producing pills with 33% drug loading and excellent sphericity. The optimized coating contained 1.6% dibutyl phthalate and 0.80% ethyl cellulose, and achieved 20.60% weight gain. The formulation exhibited <20% cumulative release in gastric and intestinal fluids, and approximately 75-78% release in colonic fluid within 10 hours. Release kinetics best fit the Weibull model (R² = 0.9785), indicating a diffusion-controlled mechanism.

This dual-responsive system overcomes the limitations of single-trigger colon-targeted formulations due to individual variability, ensuring colon-specific delivery. However, the static dissolution model may not fully replicate the dynamic colonic environment, and in vivo studies are needed to confirm therapeutic efficacy.

A pH/enzyme dual-responsive dropping pill system for colon-targeted naringin delivery was successfully developed and optimized. The formulation showed promising in vitro release profiles and holds potential for localized treatment of ulcerative colitis.