Log D analysis using dynamic approach

Ganeshkumar Krishnamoorthy; Prashanth Alluvada; Esayas Alemayehu; Shahul Hameed Mohammed Sherieff; Wasihun A Addi; Timothy Kwa; Janarthanan Krishnamoorthy

doi:10.1016/j.bbrep.2018.07.006

Log D analysis using dynamic approach

Biochem Biophys Rep. 2018 Sep 3:16:1-11. doi: 10.1016/j.bbrep.2018.07.006. eCollection 2018 Dec.

Authors

Ganeshkumar Krishnamoorthy¹, Prashanth Alluvada², Esayas Alemayehu³, Shahul Hameed Mohammed Sherieff⁴, Wasihun A Addi², Timothy Kwa², Janarthanan Krishnamoorthy²

Affiliations

¹ Curtiss-Wright Avionics and Electronics, Dublin 14, Ireland.
² Department of Bio-medical Engineering, Jimma Institute of Technology, Jimma University, Ethiopia.
³ Department of Civil & Environmental Engineering, Jimma Institute of Technology, Jimma University, Ethiopia.
⁴ School of life-sciences, B S Abdur Rahman Crescent institute of Science and Technology, Chennai, Tamil Nadu, India.

Abstract

$Log D$ the logarithm ( $\log_{10}$ ) of the distribution coefficient ( $D$ ), is one of the important parameters used in Lipinski's rule to assess the druggability of a molecule in pharmaceutical formulations. The distribution of a molecule between a hydrophobic organic phase and an aqueous buffer phase is influenced by the $pH$ of the buffer system. In this work, we used both the conventional algebraic method and the generalized 'dynamic' approach to model the distribution coefficient of amphoteric, diamino-monoprotic molecule and monoprotic acid in the presence of salt or co-solvent. We have shown the equivalence of these methods by analysing the recently reported experimental data of amphoteric molecules such as nalidixic acid, mebendazole, benazepril and telmisartan.

Keywords: Amphoteric; Diamino-monoprotic molecules; Diprotic; Dynamic approach; Log D analysis; Mono alkaline; Monoprotic; Salt effect; Solvent effect.