Abstract
Bile micelles play an important role in oral absorption of lowโsolubility compounds. Bile micelles can affect solubility, dissolution rate, and permeability. For the pHโsolubility profile in bile micelles, the HendersonโHasselbalch equation should be modified to take bileโmicelle partition into account. For the dissolution rate, in the NernstโBrunner equation, the effective diffusion coefficient in bileโmicelle media should be used instead of the monomer diffusion coefficient. The diffusion coefficient of bile micelles is 8โ to 18โfold smaller than that of monomer molecules. For permeability, the effective diffusion coefficient in the unstirred water layer adjacent to the epithelial membrane, and the free fraction at the epithelial membrane surface should be taken into account. The importance of these aspects is demonstrated here using several in vivo and clinical oralโabsorption data of lowโsolubility model compounds. Using the theoretical equations, the food effect on oral absorption is further discussed.