Log D Analysis using Dynamic Approach

Abstract

Log D is one of the important parameters used in Lipinskis rule to assess the druggability of a molecule in pharmaceutical formulations. It represents the logarithm (log10) 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.\n\nGRAPHICAL ABSTRACT\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC=\"FIGDIR/small/259770_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (17K):\norg.highwire.dtl.DTLVardef@17c4988org.highwire.dtl.DTLVardef@bf859corg.highwire.dtl.DTLVardef@1dccb4dorg.highwire.dtl.DTLVardef@a766a1_HPS_FORMAT_FIGEXP M_FIG C_FIG