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bioRxiv · 10.1101/259770

Log D Analysis using Dynamic approach

Krishnamoorthy, J.·Krishnamoorthy, G. K.·Alluvada, P.·Alemayehu, E.·hameed, S.·Alemayehu, W.·Kwa, T.
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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

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Krishnamoorthy, J., Krishnamoorthy, G. K., Alluvada, P., Alemayehu, E., hameed, S., Alemayehu, W., Kwa, T.. 2018-02-05. Log D Analysis using Dynamic approach. https://doi.org/10.1101/259770

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