Lipophilicity, logD7.4

Lipophilicity refers to the tendency of a compound to partition between a lipophilic organic phase and a polar aqueous phase. In drug development lipophilicity of a compound is represented either as partition coefficient, logP or distribution coefficient, logD. Since the majority of known drugs are at least partly charged in physiological pH, logD is more accurate descriptor of compound lipophilicity as it describes the partition of both un-ionized and ionized forms of the molecule, whereas logP only describes the partition of un-ionized molecules. Lipophilic compounds generally have a higher permeation across biological membranes than lipophobic compounds improving their oral bioavailability through better absorption in the gastrointestinal tract. We provide two different methods for determining lipophilicity: a “shake-flask” method (logP/D) and a high throughput RP-HPLC method, which results in an extrapolated logD (ElogD).