Lipophilicity of drugs: general characteristics and methods of determination

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Abstract

Background. Lipophilicity is one of the most significant and widely used physico-chemical characteristics of a drug, which determines its path in the body.

Aim. To systematize and generalize the literature data on the main parameters of lipophilicity and methods of its determination.

Materials and methods. The search for materials on the subject under study was carried out using the following search and information and library databases: PubMed, CyberLeninka, eLibrary, ResearchGate. The search for publications was carried out by keywords / phrases: “lipophilicity”, “lipophilicity of drugs”, “octanol / water distribution coefficient”, “assessment of lipophilicity”, etc.

Results. Lipophilicity shows the affinity of a compound to a lipophilic medium, and is traditionally expressed as the logarithm of the distribution coefficient of a molecule between two immiscible liquids − an organic solvent and water. There are various approaches to assessing lipophilicity. The standard method is “shaking in a flask”, which is based on the extraction of the test substance in the octanol-water system. Alternatively, reverse-phase thin-layer chromatography or high-performance liquid chromatography is used to assess lipophilicity. Chromatographic methods make it possible to determine the lipophilicity of a wide range of newly synthesized compounds and are characterized by low cost of experiments, simplicity and high accuracy. For ionized compounds, it is possible to use potentiometric approaches that are based on potentiometric titration or potential measurement through the use of ion-selective electrodes. Computational methods that provide quick information on lipophilicity are usually used for screening chemical libraries and have significant advantages over experimental methods. Many programs have been developed to calculate the logarithm of the distribution coefficient, which are freely available both in the form of software and on online platforms.

Conclusion. This review provides basic information about lipophilicity, describes key parameters and criteria for its assessment, and presents modern approaches to determining this characteristic.

About the authors

Zoya S. Shprakh

N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Author for correspondence.
Email: z.shprakh@ronc.ru
ORCID iD: 0000-0003-3034-750X
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

Maria V. Dmitrieva

N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: z.shprakh@ronc.ru
ORCID iD: 0000-0001-6740-5692
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

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