The solid dispersion of a poorly water-soluble Silybum marianum extract (SME) was prepared by a one-step fluid-bed coating technique depositing onto non-pareil pellets. In vitro evaluation indicated that this technique was highly efficient and reproducible producing pellets with acceptable appearance, flowability, friability, uniformity of drug content and enhanced dissolution. Physical characterization by DSC, powder X-ray diffractometry and FT-IR suggested the formation of a solid dispersion and possible interaction between PVP and the flavonolignans. Stress testing showed that the drug content and dissolution profiles of the SME solid dispersion pellets were sensitive to heat and humidity, while they are not affected under accelerated and long-term testing conditions. The relative bioavailability of solid dispersion pellets in dogs based on quantification of silibinin was about five-fold that of the SME suspension confirming enhanced oral bioavailability. It was concluded that the solid dispersion pellets prepared by fluid-bed coating showed favorable in vitro characteristics and enhanced oral bioavailability.