The objective of this study was to prepare a 72h-release formulation of silybin (72h-SLB) using a combination of solid dispersion, gel matrix and porous silica nanoparticles (PSNs) and to investigate the in vitro/in vivo correlations (IVIVCs). The results of scanning electron microscopy and N₂ adsorption demonstrated that empty PSNs possessed a spherical shape, a highly porous structure, a large specific surface area (385.89±1.12m²/g) and a small pore size (2.74nm on average). The in vitro dissolution profiles of both 72h-SLB and silybin-loaded PSNs in different concentrations (0.01, 0.06 and 0.08M) of Na₂CO₃ solutions revealed that 0.06M Na₂CO₃ solution was the optimal medium in which silybin could be released from 72h-SLB with first-order release kinetics and from PSNs with Higuchi kinetics. Furthermore, the IVIVCs of 72h-SLB and silybin-loaded PSNs in beagle dogs were also established. Using 0.06M Na₂CO₃ solution as the in vitro dissolution medium, a good linear relationship could be achieved for both 72h-SLB and silybin-loaded PSNs. The findings support the fact that the 72h-SLB (consisting of solid dispersion, regular gel matrix and PSNs) together with Na₂CO₃ solution as an in vitro dissolution medium can be developed into a promising formulation for poorly soluble drugs, which enjoys a good IVIVC.