The application of molecular structural predictors of intestinal absorption to screening of compounds for transdermal penetration

The Journal of Pharmacy and Pharmacology
Jeffrey E GriceMichael S Roberts

Abstract

The development of methods to predict the transport of molecules across biological membranes, without the need for time-consuming collection of experimental data, is a rapidly growing science. The use of structural characteristics of molecules has been investigated to predict the maximum transport rates of molecules across skin epidermal and intestinal membranes, known as maximum flux and maximum absorbable dose, respectively, although different approaches have been used. The aim of the present study was to determine whether the relationship between polar surface area and number of rotatable bonds of molecules and their permeability through intestinal membranes could be applied to the permeation of solutes through the epidermis following topical application. We used a published dataset of human epidermal maximum flux values for 182 solutes and stepwise regression to determine relationships between structural predictors and maximum membrane transport rates. Results showed that diffusion processes occurring across intestinal and skin epidermal membranes cannot be estimated by the same solute molecular properties, as different combinations of partitioning and diffusion processes appear to be dominating in each type of membrane. Th...Continue Reading

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Citations

Jun 26, 2020·Expert Opinion on Drug Discovery·Hanumanth Srikanth CheruvuMichael S Roberts
May 30, 2021·International Journal of Pharmaceutics·Leandro L SantosPiyush Jain
Jun 11, 2021·International Journal of Pharmaceutics·Jun-Jie ZouJing-Wei Shao
Feb 9, 2013·Molecular Pharmaceutics·Mingming ChangXin Tian

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