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-ionised and ionised forms of the molecule, whereas logP only describes the partition of un-ionised 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.
Lipophilicity (logP/D) is measured using a “shake-flask” –method. The study compound is incubated in a two-phase system under shaking, and samples collected from both phases after equilibration are analysed with LC/PDA/MS.
Physicochemical parameters, such as logP/D, are used not only for the prediction of the compound's behaviour in vivo, but also planning reliable test conditions for other in vitro assays.