Membrane permeability permeation

Although microporous membranes are a topic of research interest, all current commercial gas separations are based on the fourth type of mechanism shown in Figure 36, namely diffusion through dense polymer films. Gas transport through dense polymer membranes is governed by equation 8 where is the flux of component /,andare the partial pressure of the component i on either side of the membrane, /is the membrane thickness, and is a constant called the membrane permeability, which is a measure of the membrane s ability to permeate gas. The ability of a membrane to separate two gases, i and is the ratio of their permeabilities,a, called the membrane selectivity (eq. 9). 

An important characteristic of pervaporation that distinguishes it from distillation is that it is a rate process, not an equilibrium process. The more permeable component may be the less-volatile component. Perv oration has its greatest iitihty in the resolution of azeotropes, as an acqiinct to distillation. Selecting a membrane permeable to the minor corTiponent is important, since the membrane area required is roughly proportional to the mass of permeate. Thus pervaporation devices for the purification of the ethanol-water azeotrope (95 percent ethanol) are always based on a hydrophihc membrane. 

An internally-staged, gas-permeation module is used for the oxygen enrichment of air, using the flow arrangement shown in Fig. 5.206. Enrichment depends on differing membrane permeabilities for the oxygen and nitrogen to be separated. The permeation rates are proportional to the differences in component partial pressures. 

The in vitro measurements of permeability by the cultured-cell or PAMPA model underestimate true membrane permeability, because of the UWL, which ranges in thickness from 1500 to 2500 pm. The corresponding in vivo value is 30-100 pm in the GIT and nil in the BBB (Table 7.22). The consequence of this is that highly permeable molecules are (aqueous) diffusion limited in the in vitro assays, whereas the membrane-limited permeation is operative in the in vivo case. Correcting the in vitro data for the UWL effect is important for both GIT and BBB absorption modeling. 

In situ perfusion studies assess absorption as lumenal clearance or membrane permeability and provide for isolation of solute transport at the level of the intestinal tissue. Controlled input of drug concentration, perfusion pH, osmolality, composition, and flow rate combined with intestinal region selection allow for separation of aqueous resistance and water transport effects on solute tissue permeation. This system provides for solute sampling from GI lumenal and plasma (mesenteric and systemic) compartments. A sensitive assay can separate metabolic from transport contributions. 

The permeation rate is proportional to the partial pressure difference, the membrane permeability, its area and thickness ... 

Permeability = (permeate flow-rate/membrane area) x pressure... 

In a second approach, Sugano et al. [138] tried to consider paracellular transport in addition to transcellular permeation. The prediction of the paracellular transport potential was based on size and charge parameters together with artificial membrane permeability in relation to known human absorption values. Other groups have focused on the paracellular route by modification of the assay [26],... 

It is obvious from the above discussion that porous and dense membranes form two different cases, each with its own advantages and disadvantages. Dense membranes, (permeable only to one component) operating at optimum conditions, can be used to obtain complete conversions. However, because the permeation rate is low, the reaction rate has also to be kept low. Porous membranes (permeable to all components but at different permselectivities) are limited under optimum conditions to a maximum conversion (which is not 100%) due to the permeation of all the components. The permeation rates through porous membranes are, however, much higher than those through dense membranes and consequently higher reaction rates or smaller reactor volumes are possible. 

Here, Q is the solute concentration in the receptor cell at time t Q is the initial solute concentration of the donor cell V is volume of each half-cell A is the effective area of permeation and P is the membrane permeability coefficient. To determine the permeability coefficient, P a plot of — (V72A) In [1 — 2(Cf/CJ] versus time, was constructed. The linear portion yields a slope of the permeability coefficient, P in cm/s. 

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. 

EXTERNAL ION-PAIR RETURN HIDDEN RETURN Ion permeation across membrane, PERMEABILITY CONSTANT PERMEABILITY COEFFICIENT ION PUMPS... 

In ultrafiltration and reverse osmosis, in which solutions are concentrated by allowing the solvent to permeate a semi-permeable membrane, the permeate flux (i.e. the flow of permeate or solvent per unit time, per unit membrane area) declines continuously during operation, although not at a constant rate. Probably the most important contribution to flux decline is the formation of a concentration polarisation layer. As solvent passes through the membrane, the solute molecules which are unable to pass through become concentrated next to the membrane surface. Consequently, the efficiency of separafion decreases as fhis layer of concentrated solution accumulates. The layer is established within the first few seconds of operation and is an inevitable consequence of the separation of solvent and solute. 

Membrane permeability is one of the most important determinants of pharmacokinetics, not only for oral absorption, but also for renal re-absorption, biliary excretion, skin permeation, distribution to a specific organ and so on. In addition, modification of membrane permeability by formulation is rarely successful. Therefore, membrane permeability should be optimized during the structure optimization process in drug discovery. In this chapter, we give an overview of the physiology and chemistry of the membranes, in vitro permeability models and in silica predictions. This chapter focuses on progress in recent years in intestinal and blood-brain barrier (BBB) membrane permeation. There are a number of useful reviews summarizing earlier work [1-5]. 

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