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Mol Pharm ; 14(10): 3381-3390, 2017 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-28850240

RESUMEN

In this work we measured self-diffusion coefficients of 5 drugs (aspirin, caffeine, ethionamide, salicylic acid, and paracetamol) and 11 biologically active compounds of similar structure in deuterated water and 1-octanol by NMR. It has been found that an increase in the van der Waals volume of the molecules of the studied substances result in reduction of their diffusion mobility in both solvents. The analysis of the experimental data showed the influence of chemical nature and structural isomerization of the molecules on the diffusion mobility. Apparent permeability coefficients of the studied compounds were determined using an artificial phospholipid membrane made of egg lecithin as a model of in vivo absorption. Distribution coefficients in 1-octanol/buffer pH 7.4 system were measured. For the first time the model of the passive diffusion through the phospholipid membrane was validated based on the experimental data. To this end, the passive diffusion was considered as an additive process of molecule passage through the aqueous boundary layer before the membrane and 1-octanol barrier simulating the lipid layer of the membrane.


Asunto(s)
Permeabilidad de la Membrana Celular , Membranas Artificiales , Farmacocinética , Fosfolípidos/química , Solventes/química , Química Farmacéutica , Óxido de Deuterio/química , Difusión , Concentración de Iones de Hidrógeno , Modelos Químicos
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