A series of attempts to enhance the bioavailability of water insoluble drugs have been made by the fine grinding technique using a planetary ball mill in wet milling process. Here, the possibility of improving the dissolution properties of water insoluble drugs such as ursodeoxycholic acid (UDCA), diphenyl hydrantoin (phenytoin) and biphenyl dimethyl dicarboxylate (DDB) based on ultra-fine grinding process has been discussed with comparison to experimental data. Also examined was the intrinsic bioavailability estimated based on a molecular modeling approach and thermophysical data.