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Recently, solid self-emulsifying drug delivery system (S-SEDDS) which was prepared by incorporation of the conventional liquid self-emulsifying formulation into powder or particle has been introduced to enhance the oral bioavailability of poorly water-soluble drugs.In S-SEDDS, drug is dispersed at molecular or amorphous state in the solid matrix, and a supersaturated solution generally forms after dissolution, which is highly liable to recrystallization.Soluplus(R), a new polymer with amphiphilic properties, shows excellent solubilizing properties for poorly water-soluble drugs and subsequently to increase the dissolution and oral absorption.In this regard, Soluplus(R) may be a promising supersaturation stabilizer for S-SEDDS.The aim of the present study was therefore to construct a supersaturated solid SEDDS to improve oral absorption of model drug fenofibrate (FNB).SEDDS composed of ethyl oleate (EO) as oil, Cremophor RH40 as surfactant, and Transcutol(R) HP as cosurfactant were selected to solubilize FNB.And the fixed ratio of solid carrier to liquid SEDDS by weight of 1∶3 was adopted as the optimum formulation.A supersaturable system of FNB was formulated by screening various kinds of hydrophilic polymers and amphiphilic copolymers including Soluplus(R), as the precipitation inhibitor.Dissolution profiles of FNB from drug powder of different polymers under supersaturated condition showed that Soluplus(R) significantly enhanced the release of FNB as compared with other conventional polymers.This effect was also obviously observed in the dissolution profiles of FNB from solid self-emulsifying matrix under supersaturated condition.In vivo study in beagles demonstrated that the supersaturatable formulation exhibited 123.52% relative bioavailability as compared to conventional SEDDS.In conclusion, the supersaturatable S-SEDDS with Soluplus(R) as a supersaturation stabilizer provides an effective method to improve the absorption of poorly water-soluble drug.