Influence of surfactants in self-microemulsifying formulations on enhancing oral bioavailability of oxyresveratrol: Studies in Caco-2 cells and in vivo

Abstract

Self-microemulsifying drug delivery systems (SMEDDS) containing two types (Tween80 and Labrasol) and two levels (low; 5% and high; 15%) of co-surfactants were formulated to evaluate the impact of surfactant phase on physical properties and oral absorption of oxyresveratrol (OXY). All formulations showed a very rapid release in the simulated gastric fluid (SGF) pH 1.2. After dilution with different media, the microemulsion droplet sizes of the Tween80-based (∼26 to 36 nm) were smaller than that of the Labrasol-based systems (∼34 to 45 nm). Both systems with high levels of surfactant increased the Caco-2 cells permeability of OXY compared to those with low levels of surfactant (1.4-1.7 folds) and the unformulated OXY (1.9-2.0 folds). It was of interest, that there was a reduction (4.4-5.3 folds) in the efflux transport of OXY from both systems compared to the unformulated OXY. The results were in good agreement with the in vivo absorption studies of such OXY-formulations in rats. Significantly greater values of Cmax and AUC(0-10h) (p<0.05) were obtained from the high levels of Tween80-based (F(r,0-10h) 786.32%) compared to those from the Labrasol-based system (F(r,0-10h) 218.32%). These finding indicate the importance of formulation variables such as type and quantity of surfactant in the SMEDDS to enhance oral drug bioavailability.

Keywords: Caco-2 cells; Oral absorption; Oxyresveratrol; SMEDDS; Self-microemulsifying drug delivery system; Surfactants.