Permeability of diverse drugs through a lipid barrier: Impact of pH and cyclodextrin

Permeability Assessment of a High-Throughput Mucosal Platform

“…It was introduced in 2013 by Di Cagno and Bauer-Brandl [ 32 ] and was only introduced as a 96-well plate in 2016 [ 22 ]. Volkova et al reported the use of PermeaPad membranes coupled to Franz cells to construct predictive schemes of passive-diffusion permeation [ 33 ]. To date, however, the physical–chemical parameters regulating the diffusion mechanisms have never been well disclosed and, to the best of our knowledge, this is the first work where the permeability measured on the PermeaPad 96-well plate correlates to the physical–chemical properties of the drugs.…”

“…Surprisingly, no significant correlation was found with lipophilicity descriptors (e.g., cLogP), even though quantitative structure–permeation relationships studies proved the predictive value of lipophilicity on membrane permeation [ 34 ]. Volkova et al also reported a linear dependence of the permeability through the PermeaPad barrier on the solubility in 1-octanol [ 33 ].…”

Permeability of New Antifungal Fluconazole Derivatives through a Lipophilic Membrane: Experiment and Modeling

“…The thickness of the water layer cannot be determined precisely [ 26 ] and was assumed to be 2000 μm as the maximal possible value for in vitro conditions [ 19 ]. The thickness of the 1-octanol and water layers taken as 100 μm and 2000 μm, respectively, was successfully applied in our previous study [ 9 ], where a reliable correlation between the experimental and calculated permeability was obtained in the framework of the diffusion theory.…”

“…For example, Sugano et al [ 8 ] found the permeability of basic compounds to be higher than the value found from the 1-octanol/water partition. In addition, in our previous study of the permeability of various drugs (we studied clonixin and dofetilide as an example) through the liposome-based membrane—PermeaPad barrier—at different pHs [ 9 ], we proved that the negative surface potential of the membrane at pH 7.4 (the anionic particles of the membrane fatty acids) increases the probability of permeation of cationic species and slows down the anion movement.…”

“…Taking into account the numerous attempts to predict permeability reported in the literature [ 10 , 11 , 12 ] and our own experience [ 9 , 13 , 14 , 15 ], in the present study, we aimed to find a correlation between the permeability of a number of new fluconazole antifungal derivatives ( Figure 1 ), measured using the lipophilic PermeaPad barrier and several physicochemical properties and descriptors. In addition, we derived a reliable correlation equation for permeability prediction in the framework of the solubility–diffusion theory using the calculated diffusion coefficients in water and 1-octanol and the distribution coefficient in the 1-octanol/buffer pH 7.4 system determined experimentally in the literature [ 16 ].…”