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.
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.
Lipophilicity has impact on the solubility, absorption, membrane permeability, plasma protein binding, tissue distribution, entry into brain tissue and clearance path of the compound. It is used to predict not only its recognition with the target, but also its interaction with CYP450, HERG binding and PXR-mediated enzyme induction.
Protocol for Log D Determination
|Method||Shake Flask Assay|
|Stock Solution||10 μM|
|Calculation and Data delivery||Log D= log (Coct/Caq)|
Coct = Concentration in octanol
Caq = Concentration in aqueous buffer