Permeation Processes

Permeation process of small molecules across lipid membranes studied by molecular dynamics simulations. J. Phys. Chem. 100 (1996) 16729-16738. 

The Permeation Process Barrier polymers limit movement of substances, hereafter called permeants. The movement can be through the polymer or, ia some cases, merely iato the polymer. The overall movement of permeants through a polymer is called permeation, which is a multistep process. First, the permeant molecule coUides with the polymer. Then, it must adsorb to the polymer surface and dissolve iato the polymer bulk. In the polymer, the permeant "hops" or diffuses randomly as its own thermal kinetic energy keeps it moving from vacancy to vacancy while the polymer chains move. The random diffusion yields a net movement from the side of the barrier polymer that is ia contact with a high concentration or partial pressure of the permeant to the side that is ia contact with a low concentration of permeant. After crossing the barrier polymer, the permeant moves to the polymer surface, desorbs, and moves away. 

Elastomers can be compacted by the hydrostatic effects of the high-pressure gas, concurrently with the gas entering the elastomer as part of the permeation process... 

Lipophilicity is intuitively felt to be a key parameter in predicting and interpreting permeability and thus the number of types of lipophilicity systems under study has grown enormously over the years to increase the chances of finding good mimics of biomembrane models. However, the relationship between lipophilicity descriptors and the membrane permeation process is not clear. Membrane permeation is due to two main components the partition rate constant between the lipid leaflet and the aqueous environment and the flip-flop rate constant between the two lipid leaflets in the bilayer [13]. Since the flip-flop is supposed to be rate limiting in the permeation process, permeation is determined by the partition coefficient between the lipid and the aqueous phase (which can easily be determined by log D) and the flip-flop rate constant, which may or may not depend on lipophilicity and if it does so depend, on which lipophilicity scale should it be based ... 

Li, Y., Ma, M., Wang, X., and Chen, G. (2009) Photocatalytic activity of porous titania nanocrystals prepared by nanoscale permeation process in supercritical C02 effects of supercritical conditions. Catalysis Communications,... 

Barrier polymers, 3 375-405 applications, 3 405 barrier structures, 3 394-399 carbon dioxide transport, 3 403 flavor and aroma transport, 3 403-405 health and safety factors, 3 405 immiscible blends, 3 396-398 large molecule permeation, 3 388-390 layered structures, 3 394-396 miscible blends, 3 398-399 oxygen transport, 3 402 permanent gas permeation, 3 380-383 permeability prediction, 3 399-401 permeation process, 3 376-380 physical factors affecting permeability, 3 390-393... 

Similar to all chromatographic processes the band of solute that emerges from the column can be broadened by a number of processes, including contributions from the apparatus, flow of the solution through the packed bed of gel particles, and the permeation process. Corrections for this zone broadening may be made empirically it generally becomes unimportant when the sample has... 

The use of artificial membranes to investigate passive permeation processes has a long history, going back more than 40 years [68], The parallel artificial membrane permeation assay (PAMPA) is an application of the filter-supported lipid membrane system [149] and was first introduced by Kansy and... 

We may conclude that our findings support independent water and salt permeation processes, and suggest that the salt permeation is governed by a solution-diffusion transport mechanism. 

In a recent review of pharmacokinetics in drug discovery, Ruiz-Garcia et al. [81] compiled an exhaustive list of software resources for absorption prediction. The main topic in the described databases is transporters, in particular the ATP-binding cassette, of which the efflux transporter P-gp and the peptide transporter PEPTl are well known examples. These examples show that science is moving away from the simplistic passive transport view of permeability and towards an all-inclusive, mechanism-understanding model of absorption, which takes account of all the interactions between the agents involved in the specific permeation process. 

One of the main in vitro permeability assays used in the pharmaceutical industry has been for many years the Caco-2 monolayer. Therefore, most of the in silica models developed to predict permeability were based on Caco-2 data. Hou and Johnson produced a couple of reviews that comprehensibly summarizes the recent efforts using Caco-2 permeability data [92, 94]. All those models are designed to predict the influx or apparent permeability of drugs in the same direction as intestinal absorption occurs, that is, from the apical to the basal side of the cell line, regardless of the extent of active transport involved in the permeation process. 

In summary, in silica needs to embrace the complexity of the several membrane permeation processes that occur in viva, in order to provide the drug developers with a pure in silica decision making tool, which can predict in vivo endpoints for specific genomic profiles, exclusively from a compound s molecular structure. 

It is fairly easy to arrive at a theoretical expression for K, based on a simple model of the permeation process. We picture the colloidal particle as a sphere of radius Rs and the pore as a cylinder of radius Rc and length f, as shown in Figure 1.24a (Giddings 1991). The center of the solute particle cannot approach any closer than a distance Rv from the wall of the pore. Therefore, the radius of the pore that is accessible to the colloidal particle is (Rc — Rs). The layer of solution adjacent to the walls of the pore is off limits to the solute, so the concentration of the colloid in the pore is only a fraction of its value in the bulk solution. This fraction is K, for the sphere of radius Rs and equals the ratio of the accessible volume to the total volume of the pore ... 

Hollow fiber membranes are primarily homogeneous. In use, their lower permeability is compensated for by large surface per unit volume of vessel. Fibers are 25-250 pm outside dia, wall thickness 5-50 pm. The cross section of a vessel for reverse osmosis may have 20-35 million fibers/sqft and a surface of 5500-9000 sqft/cuft of vessel. Recently developed hollow fibers for gas permeation processes have anisotropic structures. 

Permeability measurements for polymer blends prepared by mixing different latices have been reported by Peterson (14). Interpreting transport data for such heterogeneous systems as polymer blends is extremely difficult, however (3, 9,15). The main purpose of the present investigation is, therefore, to study the applicability of gas permeation measurements to characterize polymer blends and not to evaluate the different theoretical models for the permeation process in heterogeneous polymer systems. 

The layer of water adjacent to the absorptive membrane of the enterocyte is essentially unstirred. It can be visualized as a series of water lamellas, each progressively more stirred from the gut wall toward the lumen bulk. For BCS class 2 compounds the rate of permeation through the brush border is fast and the diffusion across the unstirred water layer (UWL) is the rate-limiting step in the permeation process. The thickness of the UWL in human jejunum was measured and found to be over 500 pm [3]. Owing to its thickness and hydrophilicity, the UWL may represent a major permeability barrier to the absorption of lipophilic compounds. The second mechanism by which the UWL functions act as a barrier to drug absorption is its effective surface area. The ratio of the surface area of the UWL to that of the underlying brush border membrane is at least 1 500 [4], i.e., this layer reduces the effective surface area available for the absorption of lipophilic compounds and hence impairs its bioavailability. 

The transport of gas in polymers has been studied for over 150 years (1). Many of the concepts developed in 1866 by Graham (2) are still accepted today. Graham postulated that the mechanism of the permeation process involves the solution of the gas in the upstream surface of the membrane, diffusion through the membrane followed by evaporation from the downstream membrane surface. This is the basis for the "solution-diffusion model which is used even today in analyzing gas transport phenomena in polymeric membranes. 

Another method uses the lag time, to, from the beginning of the permeation process until the equilibrium permeation has occurred, as shown in Fig. 2.64. Here, the diffusion coefficient is calculated using... 

MESI operation requires processing of the whole sample to be extracted and has to reach steady-state permeation, which usually takes a long time. Thus, a new technical modification of MESI, called pulse introduction (flow injection-type) membrane extraction (PIME), has been developed, in which the sample is introduced to the membrane as a pulse pushed by a stream of eluent (usually water).55 This means that attaining a steady state is no longer crucial. PIME therefore provides not only a faster response and higher sensitivity, but also allows extraction of individual samples via discrete injections in addition to continuous on-line monitoring by sequential injection of a series of samples. Guo et al.56 described a mathematical model for the PIME permeation process, which showed that (a) there was a trade-off between the sensitivity and the time lag (the time taken to complete the permeation process) and (b) a large sample volume and a low flow rate enhance the sensitivity but also increase the time lag. 

Vane, L.M. and Alvarez, F.R. (2008) Membrane-assisted vapor stripping energy-efficient hybrid distillation vapor permeation processes for alcohol-water separation. Journal of Chemical Technology and Biotechnology, 83(9), 1275-1287. 

The characteristics of membrane permeation are partition, including affinity, location, specific interaction with certain phospholipids, and diffusion kinetics. Because of the complex events involved during drug absorption in vivo, true membrane permeability modeling cannot always be expected. Therefore, many attempts have been made to develop suitable in vitro systems to study the permeation process and its dependence on membrane composition and drag physicochemical properties. 

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