Enhanced oral bioavailability of rutin by a self-emulsifying drug delivery system of an extract of calyces from Physalis peruviana

Abstract

The aim of this study was to develop and optimize a self-emulsifying drug delivery system (SEDDS) containing an extract of calyces from Physalis peruviana with high mucus permeating properties to increase the bioavailability and the hypoglycemic activity of the active metabolites of the extract. The oil, surfactant, and co-solvent were selected based on solubility studies. The formulation was optimized using Box-Behnken statistical experimental design (BBD). Optimized conditions were Labrafac as oil 10% (w/w), Solutol HS 15 as surfactant 45% (w/w), propylene glycol as co-solvent 32% (w/w) and PDMSHEPMS 13% (w/w). The extract was loaded into SEDDS to 45% (w/w). The optimized SEDDS exhibited a mean droplet size of 19.5 nm, PDI of 0.20, and negative zeta potential. Furthermore, SEDDS permeating properties were investigated in porcine intestinal mucus using the Transwell® method. Extract-loaded SEDDS showed a 2.6-fold increase in mucus permeation compared to the unformulated extract. A pharmacokinetic study showed a nearly 6-fold increase in rutin oral bioavailability in comparison with the unformulated extract. Moreover, the hypoglycemic activity of the extract-loaded SEDDS was higher than that of the unformulated extract. These results indicate that incorporating an extract of calyces from P. peruviana into SEDDS is a promising strategy to improve the oral bioavailability of the active flavonoids in the extract and the hypoglycemic activity.