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

INTRODUCTION

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.

METHODS

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.

RESULTS

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.

DISCUSSION: 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.

CONCLUSION

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.