Development, optimization and evaluation of a novel polyherbal nanoemulsion for cholelithiasis

Cholelithiasis, or gallstone disease, remains a prevalent hepatobiliary disorder with significant clinical morbidity. Traditional herbal medicines, notably Picrorhiza kurroa and Terminalia arjuna, are historically used for hepatobiliary protection and anti-inflammatory benefits. However, challenges such as poor aqueous solubility and limited bioavailability of their bioactive constituents have hindered their clinical application. This study aimed to develop, optimize, and evaluate a novel polyherbal nanoemulsion system incorporating P. kurroa and T. arjuna for improved therapeutic management of cholelithiasis. Oil screening, compatibility studies (FTIR), and pseudo-ternary phase diagrams were conducted to select optimal components and Smix ratios for nanoemulsion preparation. A Box-Behnken Design (BBD) was employed for statistical optimization. Prepared formulations were characterized for droplet size, PDI, entrapment efficiency, refractive index, viscosity, pH, thermodynamic stability, in-vitro drug release, and anti-inflammatory activity via protein denaturation assay. The optimized nanoemulsion exhibited a mean droplet size of 105.0 nm, PDI of 0.212, zeta potential of -23.98 mV, viscosity of 67.05 cP, and entrapment efficiency of 85.03%. It demonstrated excellent thermodynamic stability, with no phase separation on centrifugation, heating-cooling, or freeze-thaw cycles. In vitro release studies showed 94.07% drug diffusion within 6 hours. Anti-inflammatory evaluation revealed potent protein denaturation inhibition (87.5% at 120 µg/mL) with an IC₅₀ of 43.90 µg/mL, indicating enhanced efficacy over individual extracts. The developed polyherbal nanoemulsion of Picrorhiza kurroa and Terminalia arjuna displayed superior physicochemical stability, drug release profile, and synergistic anti-inflammatory activity, offering a promising phytopharmaceutical strategy for cholelithiasis management.