Improvement of Bioavailability of Poorly Water-Soluble Drugs :Prediction of Theoretical Intrinsic Bioavailability

摘要

The aqueous solubility of poorly water-soluble drugs is an important factor of manyrnfactors affecting their bioavailability such as the solubility and rate of dissolution inrnwater. A series of attempts to enhance the bioavailability of poorly water-soluble drugsrnhave been made by the fine grinding technique using a planetary ball mill. For thernprediction of aqueous solubility, the experimental solubility data was collected andrnextracted by Tanimoto similarity filter then the QSPR approach using genetic algorithmrn(GA) was applied. The possibility of improving the bioavailability properties of therndrugs such as ursodeoxycholic acid (UDCA), diphenyl hydrantoin (phenytoin) andrnbiphenyl dimethyl dicarboxylate (DDB) based on the molecular interaction betweenrndrug and additives occurred by mechanochemical effect during ultra-fine grindingrnprocess has been discussed in comparison with experimental data and predicted data ofrnintrinsic bioavailability of the drugs based on molecular modeling approach and in vitrorntest for the drugs.