Log D Analysis Using Dynamic Approach

ABSTRACT Log D is one of the important parameters used in Lipinski’s rule to assess the druggability of a molecule in pharmaceutical formulations. It represents the logarithm ( log 10 ) of the distribution coefficient ( D ) of a molecule. The distribution coefficient is defined as the ratio of the concentration of the sum of ionized and unionized species of a molecule distributed between a hydrophobic organic phase and an aqueous buffer phase. Since the pH affects the ionic state of a molecule, log D value (which is dependent on the concentrations of the ionized species) also becomes dependent on pH. In this work, the conventional algebraic method is compared with a more generalized ‘dynamic’ approach to model the distribution coefficient of amphoteric, diamino-monoprotic molecule and monoprotic acid in the presence of salt or co-solvent. Recently reported experimental log D data of amphoteric molecules such as nalidixic acid, mebendazole, benazepril and telmisartan, were analyzed using both these approaches to show their equivalence. GRAPHICAL ABSTRACT