Enhanced oral bioavailability of silybin by a supersaturatable self-emulsifying drug delivery system (S-SEDDS)

Abstract A high payload supersaturatable self-emulsifying drug delivery system (S-SEDDS) was explored to improve the oral bioavailability of silybin, a poorly water-soluble drug candidate, employing hydroxypropyl methylcellulose (HPMC) as a precipitation inhibitor. The S-SEDDS formulation consisted of silybin, Labrafac CC, Cremophor RH40, Labrasol, and 5% HPMC. The pseudo-ternary phase diagrams were constructed to identify the self-emulsifying regions. The droplet size characterization study demonstrated that the mean droplet size of the optimized S-SEDDS formulation was smaller than the conventional SEDDS formulation upon dilution with 0.1 M HCl, largely because of the presence of the HPMC. In vitro dilution of the S-SEDDS formulation resulted in formation of a microemulsion, followed by a slow precipitation of silybin, while the conventional SEDDS formulation undergoes rapid precipitation, yielding a low silybin solution concentration. The results showed that the presence of HPMC effectively sustained the supersaturated state by retarding the precipitation kinetics. The in vivo study indicated that the area under the concentration–time curve ( AUC 0→12h ) of the silybin-S-SEDDS increased by nearly 3-fold more than those of the conventional SEDDS without the presence of HPMC at a drug dose of 533 mg/kg. This case demonstrates that supersaturatable formulations are an effective delivery approach to improve the oral bioavailability of poorly soluble drugs.