Evaluation of absorbability of poorly water-soluble drugs: Validity of theuse of additives

Apparent membrane permeation coefficients (P-app) of poorly water-soluble d rugs such as indomethacin (IDM) and triamterene (TAT) were obtained by the chamber method using an isolated rat intestinal tissue after solubilization of the drugs by additives. For the additives, sodium deoxycholate (DOC). p olyethylene glycol 600 (PEG 600), dimethylsulfoxide (DMSO), ethanol (EtOH), propylene glycol (PG), and rat bile were examined. Their concentrations we re determined in ranges considered to be appropriate from the results of in vivo experiments and physiological findings. From the correspondence betwe en this membrane permeability and in vivo bioavailability, we evaluated the validity of our in vitro experiment. On the basis of these evaluations, it was shown that 5% DMSO and 10% PEG 600, which did not affect the membrane integrity, were most appropriate additives for chamber experiments. P-app o f TDM was greater than that of TAT, indicating that the order corresponded with that of in vivo bioavailability after oral administration of their PEG 600 solutions, Accordingly, it was concluded that P-app obtained by our in vitro system can be used to assess the in vivo bioavailability.