Design, development, and optimisation of an amorphous solid dispersion-based etoricoxib bigel for targeted topical anti-inflammatory drug delivery.

BACKGROUND

Etoricoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, exhibits limited aqueous solubility that restricts its therapeutic performance in topical delivery systems.

PURPOSE: This study aimed to develop and evaluate a novel bigel-based topical delivery system incorporating pure etoricoxib and etoricoxib-loaded amorphous solid dispersion (ASD) to enhance solubility, stability, and anti-inflammatory efficacy, with an improved onset of action.

STUDY

DESIGN

A Box-Behnken experimental design was employed to optimise the bigel formulation by evaluating the effects of organogelator concentration, hydrogelator concentration, and ASD percentage on viscosity, hardness, and time required for 50% drug release.

METHODS

Bigels were prepared by blending hydrogel and oleogel phases at different ratios. The formulations were characterised for physical appearance, pH, spreadability, viscosity, and drug content. Further evaluation included rheological studies, in vitro release, and ex vivo skin permeation assessments. Dermal safety was evaluated using a skin irritation model, and anti-inflammatory activity was investigated using a carrageenan-induced paw oedema model in animals.

RESULTS

Compatibility studies confirmed the absence of any significant interaction between etoricoxib and excipients. Carbopol 940 and stearic acid, in an 80:20 ratio, were identified as the optimised hydrogelator and organogelator, respectively. The statistical model best fitting the data was a second-order interaction (2FI) model. Increasing concentrations of hydrogelator and organogelator resulted in higher viscosity and hardness, whereas an increased proportion of ASD significantly enhanced drug release. The optimized formulation achieved ~ 80% drug release within 8 h. It showed enhanced etoricoxib permeation, with Jss (14.816 µg/cm2/h) and Kp (0.004 cm/h) exceeding the marketed formulation (11.76 µg/cm2/h and 0.003 cm/h, respectively). The optimized bigel demonstrated good dermal tolerability and significantly reduced paw edema in vivo.

CONCLUSION

The developed bigel formulation exhibited favourable physicochemical and biopharmaceutical properties, indicating strong potential as an effective topical delivery system for the management of pain and inflammation.