Self‐emulsifying system for improving drug dissolution and bioavailability: in vitro/in vivo evaluation

Abstract

AbstractThe present study focuses on enhancement of the dissolution and oral absorption of poorly water‐soluble etodolac. A self‐emulsifying drug delivery system (SEDDS) composed of oil, surfactant, and co‐surfactant for oral administration was formulated. The SEDDS formulations were optimized by evaluating their ability to self‐emulsifying when introduced to an aqueous medium under gentle agitation, and by determination of particle size of the resulting emulsion. Optimized formulation of SEDDS was selected for bioavailability assessment in rabbits. Also, the anti‐inflammatory effect of SEDDS formulation was determined in rats, compared with powder drug and etodolac suspension in water (50 mg kg−1).The peak plasma concentration of 16.4±1.07 µg ml−1 appeared after 1.3±0.2 h, whereas with powder drug and etodolac suspension the values were 7.5±0.5 and 10.6±0.7 µg ml−1 appearing at 4.2±0.4 and 2.4±0.2 h, respectively. The AUC0‐8 of the etodolac SEDDS formulation was approximately 2.3 times as that of the pure drug and 1.5 times as much as that of the suspension form. There was no significant change in the elimination rate constant and the elimination half‐life. Thus, oral absorption is improved significantly using the SEDDS formulation. The anti‐inflammatory activity of SEDDS formulation was compared with etodolac suspended in water at a dose of 20 mg kg−1, using a carrageenan‐induced rat paw edema model. At 4 h, the SEDDS formulation reduced edema by 69% as compared a similar dose of etodolac suspension, which reduced edema by 45%. The results support the utility of SEDDS formulation for the oral delivery of etodolac, and potentially other lipophilic drugs. Drug Dev Res 2009. © 2009 Wiley‐Liss, Inc.