Permeability intrinsic

Structure of the medium. It is temperature-dependent, since the properties of the fluid (density and viscosity) are temperature-dependent. Hydraulic conductivity can be written more specifically in terms of the intrinsic permeability and the properties of the fluid. 

Permeability is normally determined using linear flow in the incompressible or compressible form, depending on whether a liquid or gas is used as the flowing fluid. The volumetric flowrate Q (or Q ,) is determined at several pressure drops. Q (or Q ,) is plotted versus the average pressure p . The slope of this line will yield the fluid conductivity K or, if the fluid density and viscosity are known, it provides the intrinsic permeability k. For gases, the fluid conductivity depends on pressure, so that... 

The lack of a method to determine the spatial distributions of permeability has severely limited our ability to understand and mathematically describe complex processes within permeable media. Even the degree of variation of intrinsic permeability that might be encountered in naturally occurring permeable media is unknown. Samples with permeability variations will exhibit spatial variations in fluid velocity. Such variations may significantly affect associated physical phenomena, such as biological activity, dispersion and colloidal transport. Spatial variations in the porosity and permeability, if not taken into account, can adversely affect the determination of any associated properties, including multiphase flow functions [16]. 

We have called the plot of log Co versus pH the flux factor profile, with the idea that such a plot when combined with intrinsic permeability, can be the basis of an in vitro classification scheme to predict passive oral absorption as a function of pH. This will be discussed later. 

We return to using the Kp and Kd symbols to represent the partition coefficient and the apparent partition (distribution) coefficient, respectively. The effective, apparent, membrane, and intrinsic permeability coefficients are denoted Pe, Pa, Pm, and P0, respectively, and D refers to the diffusivity of molecules. 

Figure 7.5 Intrinsic permeabilities of ionizable acids versus oil-water partition coefficients.

Figure 7.11 Intrinsic permeabilities versus alkane-water partition coefficients for drugs PAMPA filters soaked with alkane [509].

Intrinsic Permeability, Permeability-pH Profiles, Unstirred Water Layers (UWL), and the pH Partition Hypothesis... 

The membrane permeabilities Pm may be converted to intrinsic permeabilities P(h when the pKa is taken into consideration. An ionizable molecule exhibits its intrinsic permeability when it is in its uncharged form and there is no water layer resistance. The relationship between Pm and P0 is like that between the pH-dependent apparent partition coefficient (log Kd) and the true partition coefficient (log Kp), respectively. This relationship can be rationalized by the mass balance. Take, for example, the case of a monoprotic acid, HA. The total substance concentration is... 

Figure 7.34 Permeability-pH profiles of ketoprofen (a) log-log plot solid curve represents effective permeability, and the dashed curve is the membrane permeability, calculated by Eq. (7.53). The latter curve levels off at the intrinsic permeability, Pq. The effective curve levels off to approximately the unstirred water layer permeability, Pu. (b) Direct plot the inset curve for the fraction neutral substance levels of at 100% (scale not shown). [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

TABLE 7.15 Intrinsic Permeabilities and Unstirred Water Layer Permeabilities Determined from Iso-pH Dependence of Effective Permeabilities 2% DOPC in Dodecane... 

Once the 2% DOPC/dodecane permeability data have been corrected for pH and UWL effects, the resulting intrinsic permeabilities Pq should be linearly related... 

The above iso-pH measurements are based on the 2% DOPC/dodecane system (model 1.0 over pH 3-10 range). Another membrane model was also explored by us. Table 7.16 lists iso-pH effective permeability measurements using the soy lecithin (20% wt/vol in dodecane) membrane PAMPA (models 17.1, 24.1, and 25.1) The negative membrane charge, the multicomponent phospholipid mixture, and the acceptor sink condition (Table 7.1) result in different intrinsic permeabilities for the probe molecules. Figure 7.40 shows the relationship between the 2% DOPC and the 20% soy iso-pH PAMPA systems for ketoprofen. Since the intrinsic permeability of ketoprofen in the soy lecithin membrane is about 20 times greater than in DOPC membrane, the flat diffusion-limited transport region of the log Pe... 

Figure 7.39 Intrinsic permeabilities (iso-pH data analysis) versus octanol-water partition coefficients.

Table 7.17 summarizes the analysis of the gradient pH experiments. The range of intrinsic permeabilities spans 11 orders of magnitude The UWL permeabilities ranged from 16 to 52 x 10 6 cm/s. Those molecules that appeared to bind strongly to the sink-forming acceptor surfactant showed UWL Pu values that were about... 

Collander Relationship between 2% DOPC and 20% Soy Intrinsic Permeabilities... 

The 20% soy lecithin (Table 7.17) and the 2% DOPC (Table 7.15) intrinsic permeabilities may be compared in a Collander equation, as shown in Fig. 7.44. The slope of the regression line, soy versus DOPC, is greater than unity. This indicates that the soy membrane is more lipophilic than the DOPC membrane. Intrinsic permeabilities are generally higher in the soy system. Three molecules were significant outliers in the regression metoprolol, quinine, and piroxicam. Metoprolol and quinine are less permeable in the DOPC system than expected, based on their apparent relative lipophilicities and in vivo absorptions [593]. In contrast, piroxicam is more permeable in DOPC than expected based on its relative lipophilicity. With these outliers removed from the regression calculation, the statistics were impressive at r2 0.97. 

Figure 7.44 Collander relationship between intrinsic permeabilities of 20% soy lecithin versus 2% DOPC PAMPA models.

It is obvious from Equation 14.14 that the most important parameter determining the volumetric air flow rate <2W is the intrinsic permeability K of soil. At this point it is important to stress the difference between water permeability (or hydraulic conductivity) k , air permeability ka, and intrinsic permeability K. In most cases, when permeability data are provided for a type of soil or geological formation, these data are based on hydraulic conductivity measurements and describe how easily the water can flow through this formation. However, the flow characteristic of a fluid depends greatly on its properties, e.g., density p and viscosity p. Equation 14.16 describes the relationship between permeability coefficient k and fluid properties p and p ... 

The airflow equations presented above are based on the assumption that the soil is a spatially homogeneous porous medium with constant intrinsic permeability. However, in most sites, the vadose zone is heterogeneous. For this reason, design calculations are rarely based on previous hydraulic conductivity measurements. One of the objectives of preliminary field testing is to collect data for the reliable estimation of permeability in the contaminated zone. The field tests include measurements of air flow rates at the extraction well, which are combined with the vacuum monitoring data at several distances to obtain a more accurate estimation of air permeability at the particular site. 

The flow rate data can also be used to estimate the permeability of the subsurface. The required additional parameter is the value of air viscosity, i.e., pa = 1.83 x 10 4 g/(cms). The intrinsic permeability of soil is calculated from equations 14.16 and 14.15 and is found to be K = 1.34 x 10 8cm2. Care should be taken to perform the appropriate unit conversions when using Equation 14.15. 

U.S. EPA, Saturated Hydraulic Conductivity, Saturated Leachate Conductivity, and Intrinsic Permeability, EPA Method 9100, U.S. Environmental Protection Agency, Washington, DC, 1986. 

Figure 29 Intrinsic permeability of the monoester of PNU-82,899 using Caco-2 cell monolayers. A Transwell system was used with receiver sink conditions at 25°C. The initial donor concentration was 199 iM, and donor and receiver solutions were at pH 7.4.

P = permeability P0 = intrinsic permeability Ep = apparent activation energy R - the gas constant T = absolute temperature... 

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