Lactoferrin Reduces Surfactant Content in the Self-Emulsifying Drug Delivery System.

Abstract

Self-emulsifying drug delivery systems (SEDDSs) can effectively be employed to formulate drugs with poor oral bioavailability due to low aqueous solubility and high first-pass metabolism. High surfactant content is an existing challenge toward the successful application of SEDDS. A SEDDS is developed with lactoferrin, a natural emulsifier to reduce the Tween content of a fenofibrate (FEN) formulation. FEN SEDDS (SEDDS without lactoferrin) and FEN Lf-SEDDS (SEDDS with lactoferrin) were developed with 30% and 21% Tween content, respectively. Both formulations containing Crodamol GTCC as a lipid component were thermodynamically stable. No significant difference was observed in zeta potential (-9.25 to -12.63 mV), drug content (>85%), and percentage transmittance (>99%) between the two formulations. FEN Lf-SEDDS resulted in higher viscosity and larger particle size than FEN SEDDS. Solidified SEDDS with Aerosil 200 significantly improved in vitro drug release from both formulations than pure FEN. However, FEN SEDDS and FEN Lf-SEDDS did not show a significant difference in cumulative percent release or dissolution efficiency at 120 min. It can be concluded that lactoferrin containing SEDDS with 27% lesser synthetic surfactants (Tween 80 and Span 80) can result in similar physicochemical characteristics. Oral pharmacokinetic study of FEN Lf-SEDDS in a rat model resulted in 1.3 and 5.5 times higher relative bioavailability than marketed product and pure drug, respectively. The addition of lactoferrin could substitute synthetic surfactants in self-emulsifying drug delivery systems significantly.