Passive membranes

When screening for absorption by passive membrane permeability, artificial membranes have the advantage of offering a highly reproducible and high-throughput system. Artificial membranes have been compared to Caco-2 cells and for passive... 

The above rules only apply to compounds that undergo passive membrane transport... 

N. F. Ho, and P. S. Burton. Physicochemical determinants of passive membrane permeability role of solute hydrogen-bonding potential and volume, J. Med. Chem. 2001, 44, 3721-3729... 

Passive Membrane Permeability and the Polar Surface Area I 345... 

For compounds not metabolized by the gut wall, liver, or affected by transporters, a direct relationship between oral absorption and bioavailability should be observed. The calculated oral absorption, using PSA as a measure for passive membrane permeability reflecting the absorption step, relates to the in vivo observed bioavailability for three classes of compounds - angiotensin-converting enzymes (ACE) inhibitors, P-blockers, and calcium antagonists - is shown below [25],... 

The membrane is a unit of the process separated from the reactor. It maintains only the separation function (passive membrane) and there is almost no interaction between reaction and separation. In fact, we have here two different processes connected in series. Stream purification from catalyst poisoning substances or feed enrichment of a recycle stream belong to the possibilities of this configuration. 

A membrane reactor offers the possibility of combining two individual processes in the same unit operation. (1) Selective permeation (thus separation) can be coupled directly with the reaction by means of either a catalytically active membrane or of a passive membrane placed next to the... 

Recently, there is some negativity towards PAMPA [52], seemingly due to an overexpectation and misunderstanding of PAM PA and the science of passive membrane permeation [53]. PAMPA is a refined descendant of log Poet and is an improved surrogate measurement for passive transcellular permeation. PAMPA permeability usually correlates well with passive transcellular permeation. It is important to correctly understand the pros and cons of this tool and to use it appropriately in drug discovery. 

Kalyanaraman, C. and Jacobson, M.P. (2007) An atomistic model of passive membrane permeability application to a series of FDA approved drugs. Journal of Computer-Aided Molecular Design, 21, 675-679. 

Figure 8.4 Reactor types used in organic-aqueous biphasic systems (a) Emulsion reactor, (b) Lewis cell, (c) passive membrane reactor, (d) active membrane reactor. E represents enzyme molecules.

Because there are many different ways to combine a catalyst with a membrane, there are numerous possible classifications of the CMRs. However, one of the most useful classifications is based on the role of the membrane in the catalytic process we have a catalytically active membrane if the membrane has itself catalytic properties (the membrane is functionalized with a catalyst inside or on the surface, or the material used to prepare the membrane is intrinsically catalytic) otherwise if the only function of the membrane is a separation process (retention of the catalyst in reactor and/or removal of products and/or dosing of reagents) we have a catalytically passive membrane. The process carried out with the second type of membrane is also known as membrane-assisted catalysis (a complete description of the different CMRs configurations will be presented in a specific chapter). 

There is one major caveat of using the tissue culture transport experiment to study P-gp efflux that cannot be overlooked—P-gp efflux is not directly determined in this experiment. Rather, the effects of P-gp-mediated efflux activity and changes to this activity are inferred from the resulting overall transport data. Particularly with regards to substrate identification, there is the potential for false negatives. For a compound to be affected by P-gp-mediated efflux, it must reach P-gp s binding site that is within the cell. Compounds with poor membrane (transcellular) permeability are not likely to be identified as substrates (395,397). Conversely, compounds with very high passive membrane permeability can saturate P-gp efflux at low micromolar concentrations and are often not identified as substrates... 

Doppenschmitt S, Spahn-Langguth H, Regardh CG, et al. Role of P-glycoprotein-mediated secretion in absorptive drug permeability an approach using passive membrane permeability and affinity to P-glycoprotein. J Pharm Sci 1999 88 (10) 1067-1072. 

Passive membrane dialysis is usually applied batch-wise, since its driving-force is the difference in gradient concentration between the two solutions separated by the membrane. In this case, the solute (reactants and products small molecules) from a hypertonic solution (the resulting solution of the catalytic reaction) permeates through the membrane to the hypotonic side (pure solvent) until equilibrium has been achieved, whereas the nanosized catalyst remains confined inside the membrane (similar to a tea-bag see Fig. 3A). 

Fig. 3 Schematic representation of batch-wise passive membrane dialysis (A) and continuous membrane filtration dead-end-filtration (B) and loop reactor (C)...

Fig. 9 Passive membrane dialysis performed with catalyst G0-20 in a Michael 1,4-addition reaction. A Upper phase = Et20 + catalyst + product, lower phase = aqueous HC1 + side-products. B Organic phase addition into the membrane pocket . C Diffusion of the product into the beaker (charged with pure Et20), while the catalyst remains retained inside the tea-bag ...

At the end of a typical reaction, the reaction mixture was quenched with aqueous HC1 in order to form the product (Fig. 9A). The resulting organic phase was submitted to passive membrane dialysis (Fig. 9B,C) to recover the catalyst Go-20. The fraction retained by the membrane (Fig. 9C) was used in another run, where again the 1,4-addition product was formed quantitatively, proving the presence of active catalyst after recycling. 

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