In the present study, the practically insoluble drug, simvastatin (SV), and its inclusion complex with hydroxypropyl beta-cyclodextrin (HP-beta-CD) prepared using supercritical antisolvent (SAS) process were investigated to improve the aqueous solubility and the dissolution rate of drug, thus enhancing its bioavailability. Inclusion complexation in aqueous solution and solid state was evaluated by the phase solubility diagram, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The phase solubility diagram with HP-beta-CD was classified as A(L)-type at all temperatures investigated, indicating the formation of 1:1 stoichiometric inclusion complex. The apparent complexation constants (K(1:1)) calculated from phase solubility diagram were 774, 846 and 924 M(-1) at 25, 37 and 45+/-0.5 degrees C, respectively. No endothermic and characteristic diffraction peaks corresponding to SV was observed for the inclusion complex in DSC and PXRD. FT-IR study demonstrated the presence of intermolecular hydrogen bonds between SV and HP-beta-CD in inclusion complex, resulting in the formation of amorphous form. Aqueous solubility and dissolution studies indicated that the dissolution rates were remarkably increased in inclusion complex, compared with the physical mixture and drug alone. Moreover, SV/HP-beta-CD inclusion complex performed better than SV in reducing total cholesterol and triglyceride levels. This could be primarily attributed to the improved solubility and dissolution associated with inclusion complex between drug and HP-beta-CD. In conclusion, SAS process could be a useful method for the preparation of the inclusion complex of drug with HP-beta-CD and its solubility, dissolution rate and hypolipidemic activity were significantly increased by complexation between SV and HP-beta-CD.