Self-nanoemulsion containing synergistic polyherbal combinations: DoE-based formulation development and pharmacokinetics study

Polyherbal combination has been reported due to synergistic effects between Phyllanthus niruri , Centella asiatica , Curcuma xanthorrhiza, and Curcuma longa . The solubility and permeability limit the activity of those pharmacological bioactive compounds, and it improves dramatically when the absorption problem has been tackled accurately through nanoemulsion. This recent study purposed to develop a self-nanoemulsion formulation of polyherbal combination and improve the bioavailability of active pharmacological compounds. The nanoemulsion components, including oil, surfactant, and co-surfactant, were developed using an integrated statistical method, categorical model factorial design, and D-optimal design for screening and formulation development, respectively. The optimized formulation was determined based on the parameters of the self-emulsification process, droplet size and variation, zeta potential, antioxidant activity, and drug loading. The pharmacokinetics evaluation of the optimized formulation was carried out. The results revealed that modified oil reduced the droplet size and its variation. The surfactant improved the antioxidant activity, and the co-surfactant enhanced the stability of the nanoemulsion. The optimized formulation for a nanoemulsion combination of polyherbal extracts was obtained at 29.08% Capmul PG 8 NF, 35.52% Kolliphor RH 40, and 35.41% Transcutol P. The bioavailability of curcumin and phyllanthin as the main compounds in the polyherbal combination increased nearly 2 times in all pharmacokinetics parameters. This concept could be applied for bioactivity improvement through the bioavailability enhancement of the polyherbal combination via self-nanoemulsion formulation.