Permeability, determination

As more sensitive analytical methods for pesticides are developed, greater care must be taken to avoid sample contamination and misidentification of residues. For example, in pesticide leaching or field dissipation studies, small amounts of surface soil coming in contact with soil core or soil pore water samples taken from further below the ground surface can sometimes lead to wildly inaccurate analytical results. This is probably the cause of isolated, high-level detections of pesticides in the lower part of the vadose zone or in groundwater in samples taken soon after application when other data (weather, soil permeability determinations and other pesticide or tracer analytical results) imply that such results are highly improbable. 

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

Carbamazepine, antipyrine, terbutaline, and hydrochlorothiazide were treated as neutral molecules. Their effective permeabilities were corrected for the unstirred water layer using estimated unstirred water layer permeabilities, determined by the other molecules of similar lipophilicities and size. 

TABLE 7.18 Interpolated Apparent and Membrane Permeabilities Determined from Double-Sink Conditions 20% Soy Lecithin in Dodecane... 

Hussain, A. S., Methods for permeability determination A regulatory perspective. AAPS Workshop on Permeability Definitions and Regulatory Standards for Bioequivalence, Arlington, VA, Aug. 17-19, 1998. 

JH Kou, D Fleisher, GL Amidon. Calculation of the aqueous diffusion layer resistance for absorption in a tube Application to intestinal membrane permeability determination. Pharm Res 8 298-305, 1991. 

BH Stewart, OH Chan, RH Lu, EL Reyner, HL Schmid, HW Hamilton, BA Steinbaugh, MD Taylor. Comparison of intestinal permeabilities determined in multiple in vitro and in situ model Relationship to absorption in humans. Pharm Res 12 693-699, 1995. 

Coal properties (range, degree and permeability) determine the suitability of the site, either for storage or storage with only CH4 recovery. 

Several attempts have been made to estimate the dose required in humans in relation to a drug s potency, and to put this into the context of solubility and permeability for an optimal oral drug [2, 3]. A relatively simple example of this is where a 1.0 mg kg-1 dose is required in humans, then 52 pg mL"1 solubility is needed if the permeability is intermediate (20-80%) [3]. This solubility corresponds approximately to 100 pM of a compound with a MW of 400 g mol-1. Most screening activities for permeability determinations in, e.g., Caco-2, are made at a concentration of 10 pM or lower due to solubility restrictions. The first implication of this is that the required potency for these compounds needs to correspond to a dose of <0.1 mg kg-1 in humans if the drug should be considered orally active. Another implication would be the influence of carrier-mediated transport (uptake or efflux), which is more evident at low concentrations. This could result in low permeability coefficients for compounds interacting with efflux transporters at the intestinal membrane and which could either be saturated or of no clinical relevance at higher concentrations or doses. 

The advantages of the in situ techniques include an intact blood supply multiple samples may be taken, thus enabling kinetic studies to be performed. A fundamental point regarding the in situ intestinal perfusion method is that the rat model has been demonstrated to correlate with in vivo human data [46 19], Amidon et al. [36] have demonstrated that it can be used to predict absorption for both passive and carrier-mediated substrates. However, the intestinal luminal concentrations used in rat experiments should reflect adequately scaled and clinically relevant concentrations to ensure appropriate permeability determinations [50], There are limitations of the in situ rat perfusion models. The assumption involved in derivation of these models that all drug passes into portal vein, that is drug disappearance reflects drug absorption, may not be valid in some circumstances as discussed below. 

Stewart BH, Chan OH, Lu RH, Reyner EL, Schmid HL, Hamilton HW, Stein-baugh BA and Taylor MD (1995) Comparison of Intestinal Permeabilities Determined in Multiple In-Vitro and In-Situ Models—Relationship to Absorption in Humans. Pharm Res 12 pp 693-699. 

Bajka BH, Gillespie CM, Steeb CB, Read LC, Howarth GS (2003) Applicability of the Ussing chamber technique to permeability determinations in functionally distinct regions of the gastrointestinal tract in the rat. Scand J Gastroenterol 38 732-741. 

Similarly at 1.2 h the pressure was drawn down for 37 min, and dissociating hydrates replenished the pressure over the next 69 min. The response time for the pressures can be modeled as indications of reservoir permeability, determined to range from 0.001 to 0.1 mD. 

The flux solvent evolution of pure water with the transmembrane pressure across NF/LPRO membranes are reported in Fig. 6. The linear dependence of fluxes with the transmembrane pressure shows that Darcy s law is verified. As expected, the hydraulic permeabilities determined from the slopes (Table 3) show higher values for NF than LPRO membranes, due to their larger pore size. The NF90 membrane shows the higher hydraulic permeability with Z p = 14.8 Lh 1 m 2bar 1. 

Two most important properties of the wiek are the pore size and the permeability. The pore size (radius) determines the fluid pumping pressure (eapillary head) of the wiek. The permeability determines the frietional losses of the fluid as it flows through the wiek. Aetually there are several types of the wiek struetures available ineluding metal sintered powder fine fiber bundle, axially grooves, sereen mesh. 

Transient vs. Steady-State Behavior in Permeability Determinations. The foregoing derivations raise some intriguing speculations about the measurement and determination of permeabilities for the respective components in a mixture. Thus, if a true or complete steady-state condition exists during the experiment, whereby all of the feed stream passes through the membrane, then the ratio V/F = and the ratio L/F = 0. That is, it can be said that no reject phase whatsoever is produced. 

In any event, the permeability determinations of component for mixtures are apparently at variance with those determined separately for each of the pure components. It is part of the general problem so often encountered of trying to project from pure component behavior to the behavior of mixtures. 

Snowpack permeability determines air flow within the snowpack, as driven by differences in surface pressure between different parts of the snow surface. Air flow through the snow leads to the exchange of heat and of chemical species between the snow and the atmosphere and is the last physical variable discussed here. 

Figure 3 The relationship between permeability determined using Caco-2 cell mono-layers or rat intestinal perfusion and the fraction of dose absorbed in humans. The relation-ship is described in Eq. (2). (From Ref. 61.)...

Figure 15.1 shows the parameters pertinent to a field pumping test for permeability determination. One test well is required, and two observation wells are needed, both within the drawdown curve and at different radial distances from the test well. The test well is pumped at some constant rate until equilibrium elevations are attained in the observation wells. Field measurements of Q, ri, r2, hi, and h2 are taken. Permeability is computed from... 

HT-solubility/permeability First, solubility is determined at four pH values by comparing the concentration of a saturated compound solution with its dilute, known as the concentration. The filtered, saturated solution from the solubility assay is then used as input material for the membrane permeability determination. The permeability assay is a parallel artificial membrane technique whereby a membrane is created on a solid support, PAMPA. The two artificial membranes presented here model the GIT and the BBB. Data are presented for control compounds, which are well documented in the literature and exemplify a range of solubility and membrane permeability. The advantages of the combination method are (/) reduction of sample usage and preparation time, ( /) elimination of interference from compound precipitation in membrane permeability determination, Hi) maximization of input concentration to permeability assay for improved reproducibility, and (/v) optimization of sample tracking by streamlining data entry and calculations. BBB permeability ranking of compounds correlates well with literature CNS activity. 

This method is also referred to as the miscible-displacement or continuous-flow method. In this method a thin disk of dispersed solid phase is deposited on a porous membrane and placed in a holder. A pump is used to maintain a constant flow velocity of solution through the thin disk and a fraction collector is used to collect effluent aliquots. A diagram of the basic experimental setup is shown in Fig. 2-6. A thin disk is used in an attempt to minimize diffusion resistances in the solid phase. Disk thickness, disk hydraulic conductivity, and membrane permeability determine the range of flow velocities that are achievable. Dispersion of the solid phase is necessary so that the transit time for a solute molecule is the same at all points in the disk. However, the presence of varying particle sizes and hence pore sizes may produce nonuniform solute transit times (Skopp and McCallister, 1986). This is more likely to occur with whole soils than with clay-sized particles of soil constituents. Typically, 1- or 2-g samples are used in kinetic studies on soils with the thin disk method, but disk thicknesses have not been measured. In their study of the kinetics of phosphate and silicate retention by goethite, Miller et al. (1989) estimated the thickness of the goethite disk to be 80 /xm. 

The proposed ISO standard recommends that, in order to increase the accuracy of the permeability determination, the measurement is repeated at three different flowrates and a mean value is taken. It also recommends that the bed uniformity is tested by repeating measurements with different amounts of powder packed to the same porosity or under the same packing force. The porosity range should normally be between 0.45 and 0.7, and the optimum range used should be checked for every new powder. 

A thin metallic film (1000 A, carbon-to-tin ratio less than 0.3) was deposited onto polypropylene and the permeability determined. A water vapor permeability of 1.76 X 10 cm (STP) cm cm 2 S cra Hg-l was obtained, which is of the order of values usually found for metal coatings such as copper. (Table III). 

The increase in new structures generated each year has not resulted in the expected increase of marketed new drugs annually. This has amongst others been attributed to poor pharmacokinetic (PK) properties of the CDs, and as much as 40% of the attrition rate of CDs has been related to poor PK profiles [1]. Given this, reliable screening filters for factors such as absorption, distribution, metabolism, elimination/excretion, and toxicity (ADMET) are highly desirable [2-4], Indeed, the considerable effort that has been invested in the development of experimental absorption filters, for example, cell monolayers for permeability determinations [5, 6] and the turbidimetric method for solubility measurements [7],... 

There is some recent evidence that the chloride permeability determined by exchange measurements is much greater than that determined by net translocation (38). However, throughout this work a counteranion was always available, so the use of the high (10"4 cm/sec) permeability value seems justified since all movements of chloride ions occur under exchange conditions. 

Elsworth, D. Lee, D.S. 2003. Permeability determination from On-the-fly piezocone sounding, (under review). Journal of Geotechnical and GeoEnvironmental engineering. 

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