Transport membrane permeation

Basically, the spiral-wound configuration consists of a jelly roll-like arrangement of feed transport material, permeate transport material and membrane material. At the heart of the wall is a perforated permeate collector tube. Several rolls are usually placed end to end in a long pressure vessel. 

It should be apparent that the principles of selective ion transport are independent of the specific models being treated here and that many of these principles are at variance with what were traditional views on the basis of selective membrane permeation by inorganic ions. Thus, the concept of selectivity among monovalent cations being based on values of hydrated radii is replaced by the... 

The evaluation of the apparent ionization constants (i) can indicate in partition experiments the extent to which a charged form of the drug partitions into the octanol or liposome bilayer domains, (ii) can indicate in solubility measurements, the presence of aggregates in saturated solutions and whether the aggregates are ionized or neutral and the extent to which salts of dmgs form, and (iii) can indicate in permeability measurements, whether the aqueous boundary layer adjacent to the membrane barrier, Umits the transport of drugs across artificial phospholipid membranes [parallel artificial membrane permeation assay (PAMPA)] or across monolayers of cultured cells [Caco-2, Madin-Darby canine kidney (MDCK), etc.]. 

In an effort to address the poor membrane permeation of L-767,679, the benzyl ester pro-drug, L-775,318 was synthesized (Fig. 13.2) The latter compound exhibited significant lipophilicity (log P = 0.7) that was consistent with improved potential to cross the enterocyte membrane. However, this did not lead to a marked improvement in absorption potential (in the rat), as intestinal hydrolysis and counter-transport combined to prevent significant passage of the compound across Caco-2 cells and the rat gut. 

Continuous Multicomponent Distillation Column 501 Gas Separation by Membrane Permeation 475 Transport of Heavy Metals in Water and Sediment 565 Residence Time Distribution Studies 381 Nitrification in a Fluidised Bed Reactor 547 Conversion of Nitrobenzene to Aniline 329 Non-Ideal Stirred-Tank Reactor 374 Oscillating Tank Reactor Behaviour 290 Oxidation Reaction in an Aerated Tank 250 Classic Streeter-Phelps Oxygen Sag Curves 569 Auto-Refrigerated Reactor 295 Batch Reactor of Luyben 253 Reversible Reaction with Temperature Effects 305 Reversible Reaction with Variable Heat Capacities 299 Reaction with Integrated Extraction of Inhibitory Product 280... 

The successful application of in vitro models of intestinal drug absorption depends on the ability of the in vitro model to mimic the relevant characteristics of the in vivo biological barrier. Most compounds are absorbed by passive transcellular diffusion. To undergo tran-scellular transport a molecule must cross the lipid bilayer of the apical and basolateral cell membranes. In recent years, there has been a widespread acceptance of a technique, artificial membrane permeation assay (PAMPA), to estimate intestinal permeability.117118 The principle of the PAMPA is that, diffusion across a lipid layer, mimics transepithelial permeation. Experiments are conducted by applying a drug solution on top of a lipid layer covering a filter that separates top (donor) and bottom (receiver) chambers. The rate of drug appearance in the bottom wells should reflect the diffusion across the lipid layer, and by extrapolation, across the epithelial cell layer. 

Another in vitro method for permeability screening was parallel artificial membrane permeation assay (PAMPA) initially reported by Kansy. In a PAMPA permeability screen, the Caco-2 cell mono-layer membrane is replaced by an artificially generated membrane. Versions of different artificial membranes that lack active transporter systems and pores have been developed to mimic the in vivo transcellular intestinal epithelial cell barrier. Therefore, the PAMPA screen only measures the intrinsic... 

Poor intestinal absorption of a potential drug molecule can be related to poor physicochemical properties and/or poor membrane permeation. Poor membrane permeation could be due to low paracellular or transcellular permeability or the net result of efflux from transporter proteins including MDRl (P-gp) or MRP proteins situated in the intestinal membrane. Cell lines with only one single efflux transporter are currently engineered for in vitro permeability assays to get suitable data for reliable QSAR models. In addition, efforts to gain deeper insight into P-gp and ABC on a structural basis are going on [131, 132]. 

Sugano et al. studied the membrane permeation of 51 benzamidine-based thrombin inhibitors in a rat everted sac permeability model [197]. They reported significant membrane permeabilities in this in vitro model, which they attributed to passive paracellular transport, a different absorption mechanism to transcellular permeability. 

C. Membrane permeation receptor mediated endocytosis, vesicular uptake, and transport... 

Fig. 19.3 The solution-diffusion transport model in pervaporation. a Solution of compounds from the feed phase into the membrane surface, b Diffusion across the membrane barrier, c Desorption from the membrane permeate (downstream) side into the permeate phase...

Ester prodrugs are employed to enhance membrane permeation and transepithelial transport of hydrophilic drugs by increasing the lipophilicity of the parent compound, resulting in enhanced transmembrane transport by passive diffusion. For example, pivampicillin, a pival-oyloxymethyl ester of ampicillin, is more lipophilic than its parent ampicillin and has demonstrated increased membrane permeation and transepithelial transport in in vivo studies.103... 

Figure 11.26 Performance of a 37 m2 hollow fiber silver-nitrate-impregnated facilitated transport membrane for the separation of propylene/propane mixtures. The feed pressure was 5-13 atm the permeate was a hexane liquid sweep stream. The vertical dotted lines show when the membrane was regenerated with fresh silver nitrate solution [27]. Reprinted with permission from R.D. Hughes, J.A. Mahoney and E.F. Steigelmann, Olefin Separation by Facilitated Transport Membranes, in Recent Developments in Separation Science, N.N. Li and J.M. Calo (eds) (1986). Copyright CRC Press, Boca Raton, FL...

Some of the variables that are important for the subsequent discussion are recalled here. The membrane properties are related to the mass transport of the different chemical species through the membrane itself or its separating layer (for an asymmetric or multilayer membrane). Permeability and selectivity were defined for the mass transport by permeation both depend on the membrane nature and morphology that impose the specific transport mechanism driving the permeation of which it is characteristic. Table 13.2 reports the permeability coefficient, selectivity and permeating driving force of some permeation mechanisms. 

Fundamental aspects of chemical membrane reactors (MRs) were introduced and discussed focusing on the peculiarity of MRs. Removal by membrane permeation is the novel term in the mass balance of these reactors. The permeation through the membrane is responsible for the improved performance of an MR in fact, higher (net) reaction rates, residence times, and hence improved conversions and selectivity versus the desired product are realized in these advanced systems. The permeation depends on the membranes and the related separation mechanism thus, some transport mechanisms were recalled in their principal aspects and no deep analysis of these mechanisms was proposed. 

Many factors including partition characteristics, degree of ionization, molecular size etc. influence the transport of drugs across biological membranes. Permeation of intact mucosa may also involve passive diffusion, intercellular movement, transport through pores or other mechanisms. The objective of the studies reported here was to employ the dog model to investigate these factors in a systematic and experimentally well-controlled fashion. The non-steriodal anti-inflammatory drug, diclofenac sodium, was selected as a test compound in this evaluation process. 

If transport through a membrane involving both surface reaction (dissociation) and diffusion was limited by surface reactions, then n = 1. If transport was diffusion-limited, then n = 0.5. Intermediate values of n (0.5proton transport membranes was modeled with the same form of the equations used to model diffusion membranes, Eqns. 3 and 4. Values of k H2 and n were determined from Eqn. 3. The concentration of hydrogen on the permeate-side was insignificant relative to the concentration on the retentate-side. Therefore was equated to... 

Subsequent studies of these proton-transport membranes will be conducted over a wide range of hydrogen partial pressures on the permeate side. This will allow assessment of whether the driving force for hydrogen permeance is more accurately represented as the natural logarithm of the ratio of the hydrogen partial pressures on the retentate and permeate sides, as observed in ion transport oxygen membranes. 

Sometimes it is useful to apply a combination of the descriptors based on the global properties of the molecule and those based on a pharmacophoric representation. Conceptually, the global properties would better describe the imtial passive membrane permeation required to reach the site of action. Then, the specific protein interactions could be explained by the pharmacophoric descriptors. This has been demonstrated successfully in the P-glycoprotein case [26], where two processes are important for the transport passive transport to the cell and active... 

Generally speaking, two principal mechanisms operate in the biology of membrane processes, such as membrane transport and permeation. One involves a network of active sites and operates by metabolic energy, and it is referred to as active another is directed by passive diffusion, and it is called passive. This passive mechanism is determined by various aspects of lipid dynamics and lipid-protein interactions, and it can be described in quantitative terms of chemical and phase equilibrium and molecular physics. However, in the highly anisotropic... 

Possible transport mechanisms in a fluid system through the membrane pores are multiple. They vary to a great extent with the membrane pore size and, to a less extent, with chemical interaction between the transported species and the membrane material. Under the driving force of a pressure gra nt, permeants (whether in the form of solvents, solutes or gases) can transport across a membrane by one or more of the mechanisms to be discussed below. The degree by which they affect permeability and permselectivity depends on the operating conditions, membrane characteristics and membrane-permeating species interactions in the application environment. 

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