Solubility parameter and oral absorption.

The solubility parameter (delta) for a series of structurally diverse compounds was determined using a group contribution method devised by Fedors, and then related to the degree of oral absorption. Solubility parameter values around 22.5 MPa1/2 were shown to be associated with compounds that were well absorbed, whereas, compounds with a high delta (30-40 MPa1/2) showed poor absorption. A correlation was also evident between the number of H-bonding acceptor groups in a compound and the extent of oral absorption. Surprisingly, when C Log P values were used in comparison, no obvious correlation existed. The conclusion from this work is that the solubility parameter may be a more reasonable predictor of absorption than using C Log P values.