Preparation and Evaluation of Self-emulsifying Drug Delivery System (SEDDS) of Cepharanthine

Abstract

The aim of this article was to design a self-emulsifying drug delivery system (SEDDS) of loaded cepharanthine (CEP) to improve the oral bioavailability in rats. Based on the solubility determination and pseudo-ternary phase diagram, isopropyl palmitate (IPP) was chosen as the oil phase. Meanwhile, Cremophor RH40 and Macrogol 200 (PEG 200) were chosen as the emulsifier and co-emulsifier, respectively. This prescription was further optimized by using central composite design of response surface methodology. The optimized condition was CEP:IPP:Cremophor RH40:PEG 200=3.6:30.0:55.3:11.1 in mass ratio with maximum drug loading (36.21 mg/mL) and the minimum particle size (36.70 nm). The constructed CEP-SEDDS was characterized by dynamic light scattering, transmission electron microscopy, in vitro release and stability studies. The dissolution level of CEP-SEDDS was nearly 100% after 30 min in phosphate-buffered saline (PBS, pH 6.8) which was higher than that of the pure CEP (approximately 20%). In addition, in vivo pharmacokinetic study in rats showed that CEP-SEDDS dramatically improved bioavailability compared with active pharmaceutical ingredient (API) (the relative bioavailability was 203.46%). In this study, CEP-SEDDS was successfully prepared to enhance the oral bioavailability which might facilitate to increase its better clinical application. [Figure not available: see fulltext.]