Improved dissolution and bioavailability of silymarin delivered by a solid dispersion prepared using supercritical fluids

摘要

Abstract The objective of this study was to improve the dissolution and bioavailability of silymarin (SM). Solid dispersions (SDs) were prepared using solution-enhanced dispersion by supercritical fluids (SEDS) and evaluated in?vitro and in?vivo, compared with pure {SM} powder. The particle sizes, stability, and contents of residual solvent of the prepared SM-SDs with {SEDS} and solvent evaporation (SE) were investigated. Four polymer matrix materials were evaluated for the preparation of SM-SD-SEDS, and the hydrophilic polymer, polyvinyl pyrrolidone K17, was selected with a ratio of 1:5 between {SM} and the polymer. Physicochemical analyses using X-ray diffraction and differential scanning calorimetry indicated that {SM} was dispersed in {SD} in an amorphous state. The optimized SM-SD-SEDS showed no loss of {SM} after storage for 6 months and negligible residual solvent (ethanol) was detected using gas chromatography. In?vitro drug release was increased from the SM-SD-SEDS, as compared with pure {SM} powder or SM-SD-SE. In?vivo, the area under the rat plasma {SM} concentration-time curve and the maximum plasma {SM} concentration were 2.4-fold and 1.9-fold higher, respectively, after oral administration of SM-SD-SEDS as compared with an aqueous {SM} suspension. These results illustrated the potential of using {SEDS} to prepare SM-SD, further improving the biopharmaceutical properties of this compound.