Permeability coefficient modeling comparisons

Experimental Results and Comparisons with the Classical Lipid Barrier Model. Some typical experimental data are presented in Figure 1 for the transport of g-estradiol. In each of the experiments a lag-time of 1.5 to 2.5 hours were followed by linear steady state fluxes. The effective permeability coefficient, Peff> was calculated from such data using Equation 1 under sink conditions (i.e., Cj/K Cr/Kr where, Kj is the partition coefficient between membrane and donor phase and Kr the partition coefficient between membrane and receiver phase.)... 

A comparison of the permeability coefficients of a series of xenobiotics using Caco-2 cells and an in situ human jejunal perfusion showed that the permeability of compounds with high or complete absorption differed 2- to 4-fold between the in vitro and in situ models, but poorly absorbed compounds differed as much as 30- to 80-fold [18]. Measurement of permeability using Caco-2 cells, therefore, affords only a qualitative comparison. 

Animal Models A Comparison of Permeability Coefficients for Excised Skin... 

Vecchia BE, Bunge A. Animal models a comparison of permeability coefficients for excised skin from humans and animals. In Riviere JE, editor. Dermal absorption models in toxicology and pharmacology. Boca Raton CRC Press 2006. p. 305-33. 

Since the widely accepted in vitro permeability model in the pharmaceutical industry is based on the use of cultured cells, such as Caco-2 or MDCK, it was appropriate to analyze the regression correlation coefficients based on the comparisons of Caco-2 log Pe and the log Pe values based on the human jejunal measurements [56]. 

Wohnsland and Faller ([175] performed measurements using a thin (9-10 //in) supported, phospholipid-free hexadecane layer. To validate their model, they used 32 well-characterized chemically diverse compounds. The permeability values obtained with their model could be correlated with known human absorption values if the maximum permeability obtained at different pH was taken into account. However, several disadvantages are related to this method. For hydrophilic drugs, hexadecane by itself has an increased barrier function in comparison with membranes. In addition, the hexadecane layers are not very stable, which makes this assay difficult to apply as a routine screening method. The advantage of this PAMPA setup is that it appears to be a satisfactory substitute for obtaining alkane-water partition coefficients, which are usually very difficult to measure directly, due to the poor solubility of drug molecules in alkanes. 

Instead of the dilute solution approach above, concentrated solution theory can also be used to model liquid-equilibrated membranes. As done by Weber and Newman, the equations for concentrated solution theory are the same for both the one-phase and two-phase cases (eqs 32 and 33) except that chemical potential is replaced by hydraulic pressure and the transport coefficient is related to the permeability through comparison to Darcy s law. Thus, eq 33 becomes... 

Figure 4.8 A shows a comparison of the experimental and model data. The figure demonstrates that it is only possible to describe the low pressure flux behavior of the system with the inclusion of activity coefficients, indicating that the system is not ideal. Other parameters in the model, such as the permeability of the solvent and the solute, were varied to check whether they could be responsible for this effect. However, it was found to be impossible to describe the data by alteration of the two permeabilities or the mass transfer coefficient. Equally, it is only possible to describe the high-pressure, concentration polarization effect with the inclusion of mass transfer effects. The overall system requires both ac-...

To understand the effect of network structure on permeability, the diffusion coefficients for each system were calculated based on independent sorption studies, and the result is presented in Figure 35.6b. Comparison with Figure 35.6a. reveals similar trends such that the observed permeability variation can be attributed mostly to a change in penetrant diffusivity in the networks. In a homogeneous blend, gas transport properties (X) such as permeability or diffusivity are often modeled empirically as (Paul, 1984)... 

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