Development and physicochemical characterization of berberine–ellagic acid phytosomes incorporated into hydrogel for topical drug delivery

This study aimed to develop and optimize a phytosome-based hydrogel containing berberine and ellagic acid for topical drug delivery. Preformulation studies, including melting point, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), UV spectroscopy, solubility, and drug–excipient compatibility, were performed to characterize the drugs and assess their suitability for formulation development. Berberine–ellagic acid phytosomes were prepared using the thin-film hydration method and optimized using a ۲³ full factorial design by evaluating the effects of soya lecithin concentration, α-tocopherol acetate concentration, and drug:phospholipid ratio on particle size and entrapment efficiency. The optimized F۶ formulation exhibited a particle size of ۱۷۶.۹ nm, Polydispersity Index (PDI) of ۰.۲۱۷, zeta potential of −۳۱.۷ mV, and entrapment efficiency of ۸۶.۳% for berberine and ۸۴.۷% for ellagic acid. The SEM analysis demonstrated predominantly spherical vesicles with a uniform morphology. The phytosome-loaded hydrogel had a pH of ۶.۴۵ ± ۰.۰۴, viscosity of ۱۴۵۸ ± ۱.۱۵ cps, drug content of ۹۵.۸۶ ± ۰.۵۲% for berberine and ۹۴.۹۷ ± ۰.۶۱% for ellagic acid, excellent spreadability, good extrudability, and homogeneous consistency. The optimized hydrogel exhibited sustained in vitro drug release, reaching ۹۵.۵۸% for berberine and ۹۶.۷۷% for ellagic acid over ۱۲ h. Drug release followed the Higuchi model for berberine and zero-order kinetics for ellagic acid. Accelerated stability studies demonstrated minimal changes in physicochemical characteristics over three months. Overall, the developed phytosome-loaded hydrogel demonstrated favorable physicochemical characteristics, controlled drug release, and good stability, supporting its potential as a topical drug-delivery system.

کلیدواژه ها:

Berberine ، ellagic acid ، Phytosomes ، Hydrogel ، Topical drug delivery ، Thin-film hydration ، Factorial design ، Controlled drug release ، Nanocarrier system