Institute of Solution Chemistry, Russian Academy of Sciences , 153045 Ivanovo, Russia.
Mol Pharm. 2017 Oct 2;14(10):3381-3390. doi: 10.1021/acs.molpharmaceut.7b00401. Epub 2017 Sep 8.
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.
在这项工作中，我们通过 NMR 测量了 5 种药物（阿司匹林、咖啡因、乙胺丁醇、水杨酸和对乙酰氨基酚）和 11 种具有相似结构的生物活性化合物在氘化水中和 1-辛醇中的自扩散系数。结果表明，研究物质的分子范德华体积的增加导致它们在两种溶剂中的扩散迁移率降低。实验数据分析表明，分子的化学性质和结构异构化对扩散迁移率有影响。使用由卵磷制成的人工磷脂膜作为体内吸收模型，测定了研究化合物的表观渗透系数。在 1-辛醇/缓冲液 pH7.4 体系中测量了分配系数。首次基于实验数据验证了通过磷脂膜的被动扩散模型。为此，将被动扩散视为分子在通过膜之前通过水边界层和模拟膜脂质层的 1-辛醇屏障的附加过程。
