Formulation and Optimization of a Rifaximin Solid Dispersion-Based Hydrogel for Topical Delivery

Background

Rifaximin is a poorly water-soluble antibiotic that limits dissolution, formulation flexibility, and topical delivery. Enhancing its solubility is essential to improve therapeutic performance in localized applications.

Materials and Methods

Solid Dispersions (SDs) were prepared using five hydrophilic polymers at drug-to-polymer ratios of 1:0.5-1:1.5 (w/w) by solvent evaporation. SDs were characterized by FTIR, XRD, and DSC. The optimized SD was incorporated into hydrogels and optimized using a 3² factorial design with locust bean gum (2-4% w/v) and xanthan gum (0.2-0.4% w/v). Formulations were evaluated for drug content, pH, viscosity, in vitro release, and accelerated stability (40ºC/75% RH, 6 months).

Results

The PVA-based SD (1:1.5) showed the highest solubility (>300 µg/mL; ~35-40-fold increase) due to amorphization and improved drug-polymer interactions. Hydrogels exhibited skin-compatible pH and pseudoplastic behavior. Drug release ranged from 23% to 47%, significantly higher than pure drug gel. Polymer concentration significantly affected viscosity and release. The optimized formulation (F3) showed balanced properties and stable performance.

Conclusion

Solid dispersion-loaded hydrogels effectively enhance rifaximin solubility and support improved topical delivery, offering a promising strategy for poorly water-soluble drugs.