Measurement permeability methods

The physical characterisation of membrane structure is important if the correct membrane is to be selected for a given application. The pore structure of microfiltration membranes is relatively easy to characterise, SEM and AFM being the most convenient method and allowing three-dimensional structure of the membrane to be determined. Other techniques such as the bubble point, mercury intrusion or permeability methods use measurements of the permeability of membranes to fluids. Both the maximum pore size and the pore size distribution may be determined.1315 A parameter often quoted in manufacturer s literature is the nominal... 

Three related methods based on the quasiisostatic method are used to measure permeability. The most commonly used technique allows the permeant gas or vapor to flow continuously through one chamber of the permeability cell. The gas or vapor permeates through the sample and is accumulated in the lower-concentration chamber. At predetermined time intervals, aliquots are withdrawn from the lower cell chamber for analysis. The total quantity of accumulated permeant is then determined and plotted as a function of time. The slope of the linear portion of the transmission-rate profile is related to the sample s permeability. 

There are various methods for the determination of the surface area of solids based on the adsorption of a mono-, or polymolecular layer on the surface of the solid. These methods do not measure the particle diameter or projected area as such, but measure the available surface per gram or milliliter of powder. The surface measured is usually greater than that determined by permeability methods as the latter are effectively concerned with the fluid taking the path of least resistance thru the bed, whereas the adsorbate will penetrate thru the whole of the bed as well as pores in the powder particles. These methods appear to be more accurate than surface areas calculated from weight averages or number averages of particle size because cracks, pores, and capillaries of the particles are included and are independent of particle shape and size... 

The determination of the specific surface area of a powder by air permeability methods essentially involves the measurement of the pressure drop across a bed of the powder under carefully controlled flow conditions. The data obtained are substituted in the Kozeny-Carman equation to estimate the specific surface area. Permeability methods have certain advantages, one of them being that the equipment used for carrying out the measurements is cheap and robust. Another advantage is that sample problems are minimized because a large sample of powder is required to be used for analysis. 

Permeability is a property closely tied to the environment of the epithelial cell surface. There is little point in measuring permeability at pH 1.7, if the microclimate barrier has pH >5 and <8, averaging 6. An in vitro permeability screen based on donor pH 5.0-7.4 and acceptor pH 7.4 seems about right. It will be useful to correct the data for the unstirred water layer effect, using computational methods. 

The method described here provides a convenient means of determining the specific filtration resistance of fairly dilute suspensions. Results for clay suspensions flocculated by cationic polymers show that the specific resistance gives a sensitive indication of flocculation and is a useful guide in the selection of optimum flocculant concentrations. In a series of trials not reported here, it has been shown that the specific resistance results are very well matched by re-filtration rate data, as expected. The results also agree well with other, unrelated techniques. For more concentrated suspensions, some discrepancies have been found between permeability methods and other measures of flocculation (4). 

Lea, F. M. and Nurse, R. W. Trans. Inst. Chem. Eng. 25 (1947). Supplement Symposium on Particle Size Analysis, pp. 47-63. Permeability methods of fineness measurement. 

Zhang H, Robinson JR (1996) In vitro methods for measuring permeability of the oral mucosa. In Rathbone MJ (ed.), Oral Mucosal Drug Delivery. Marcel Dekker, New York, pp 85-100... 

In the gut sac technique, animal intestinal segments are divided into 2-cm sacs by tying off each end. The sacs, with or without musculature, can be everted or not to measure directional drug transport into or out of the sacs. The sacs are placed in a vessel containing an oxygenated buffer and transport is measured with normalization for the sac size. The intestinal gut sac method is a relatively fast and inexpensive technique for measuring permeability that includes all intestinal cell types and mucus layer. 

Permeability and solubility measurements Permeability of the free films for water vapour was measured by means of the wet cup method (15). Oxygen permeability was measured using the Polymer Permeation Analyser of Dohrmann Envlrotech (16,17). Results are summarized In Table I. 

Unfortunately the number of in silica modeling studies on brain membrane permeability is significantly smaller than for human intestinal absorption, resulting in a lack of consensus about how to assess brain penetration (both in vitro and in vivo) and the intrinsic difficulty of measuring this particular endpoint, which overall results in a low turnover of data generation that could be used to build in silica models [95, 96]. For this reason, the in silica models used to assess brain permeability in the discovery process focus normally on P-gp efflux and some measure of in vitro membrane permeability, methods which are reviewed in the next section. 

In a discussion of permeability it is important to recognize that we deal with operational definitions, since the act of measurement influences the state of the system. In your case, applying an electrical potential gradient and performing electrodialysis alter the distribution of ionophore within the membrane. I wonder whether you have attempted to measure permeability by isotopic tracer techniques In this method the distribution of ionophore would not be influenced. Furthermore, information can be obtained on the question of carriers versus channels or pores. It should not be difficult to determine the extent of possible isotope interaction between tracer species and abundant species in the membrane as discussed by Kedem and Essig [J. Gen. Physiol., 48, 1047 (1965)]. Positive isotope interaction would tend to suggest the presence of channels or pores, negative isotope interaction the presence of carriers. 

Air Permeability. Air permeability is an important parameter for certain fabric end uses, eg, parachute fabrics, boat sails, warm clothing, rainwear, and industrial air filters. Air permeability of a fabric is related to its cover, or opacity. Both of these properties are related to the amount of space between yams (or fibers in the case of nonwovens). The most common method for specifying air permeability of a fabric involves measuring the air flow per unit area at a constant pressure differential between the two surfaces of the fabric. This method, suitable for measuring permeability of woven, knitted, and nonwoven fabrics, is described in ASTM D737. Units for air permeability measured by this method are generally abbreviated as CFM, or cubic feet per square foot per minute. 

As has been indicated, Carman obtained excellent agreement with his equation using measurable surfaces. Nevertheless, there are a number of difficulties inherent in permeability methods. These concern the evaluation of the voids and the shape of the particulate matter for which the surface is to be determined. The method cannot be used for disk-like or flat material which packs in peculiar fashion since only external surface is measured. In this respect it differs from the solubility method described earlier and the adsorption method discussed in the next paragraph. Theoretically, permeability methods should give higher surface values than statistical determinations, but lower values than the two mentioned. 

Particle Surface Area Determination Methods From the standard definitions of particle surface area, it can be seen that various determination methods are used for surface area measurement, such as adsorption (including Langmuir s equation for monolayer adsorption and the BET equation for multilayer adsorption), particle size distribution, and permeability methods. The different methods are rarely in agreement because the value obtained depends upon the procedures used and also on the assumptions made in the theory relating the surface area to the phenomena measured. The most common methods used for measuring particle surface area are described below. 

The accuracy of the permeability method depends on the available relationship between the permeability parameters B0 and Kt and the structural parameters of porous media. When the pore texture is not sufficiently random and uniform, the accuracy of Equations 3.3 and 3.6 (and consequently of the method) becomes poor. This is a serious disadvantage of the permeability method, compared to the adsorption method, which does not depend on the pore texture. Nevertheless, permeability measurements are indicative of the porous structure and are useful for the determination of the parameters of the transport models. Various other experiments on flow and diffusion are also indicative of the texture of the porous particles. Some are discussed in Chapter 5. 

The specific surface area of eement is eommonly determined directly by air. permeability methods. In the Lea and Nurse method (LI 5). a bed of cement / of porosity 0.475 is eontained in a cell through which a stream of air is f passed, and steady flow established. The specific surface area is caleulated ( from the density of the eement, the porosity and dimensions of the bed of j powder, the pressure differenee aeross the bed, and the rate of flow and ] kinematie viscosity of the air. In the Blaine method (B36), a fixed volume of I air passes through the bed at a steadily deereasing rate, whieh is controlled / and measured by the movement of oil in a manometer, the time required i being measured. The apparatus is ealibrated empirically, most obviously / using a cement that has also been examined by the Lea and Nurse method. The two methods gave elosely similar results. The Blaine method, though not absolute, is simpler to operate and automated variants of it have been devised. 

Carman s Gas Permeability Method. A gas or a wetting liquid is made to flow through the porous material in a tube by applying vacuum or pressure. The pressure drop or flow rate is measured. For pigments, a modified procedure is used in which mainly nonlaminar flow takes place [1.16]. For standards, see Table 1.1 ( Specific surface Permeability techniques ). 

Weiland [42] used a similar idea but based on the Blaine permeability method. An automatic weigher produced a packed bed of powder, of known voidage, in a standard cell. Air was drawn through the bed by the passage of water from one reservoir to another. After a certain volume of air had passed through the bed, measured by a certain volume of water flowing, the time required was converted to an electrical proportionality... 

Gas permeability method. Like the gas flow method, this technique is also based on the measurement of the flow rate of a gas through a porous medium such as a membrane. The flow rate is monitored as a function of the pressure drop across the thickness of the membrane. But unlike the gas flow method, the gas used in this method is a pure, nonadsorbable and noncondensable gas. 

The permeability methods measure only that portion of the surface which is in contact with the flowing fluid. Pores within the particles do not contribute to the pressure drop (Figure 24a). The same limitations apply to the photometric methods where pores or concave parts of the particle shape are not detected because, in reality, the projection area of the particles is determined. In comparison, during gas adsorption, the ions or molecules penetrate deep into the pores and cover the entire particle surface irrespective of shape (Figure 24b). Therefore, depending on the dimensions of the pores and ions or molecules, much higher surface areas are measured with the adsorption methods than with the two other procedures. 

Permeability can be assessed by pharmacokinetic studies (for example, mass balance studies), or intestinal permeability methods, e.g. intestinal perfusion in humans, animal models, Caco 2 cell lines or other suitable, validated cell lines. In vivo or in situ animal models or in vitro models (cell lines) are only considered appropriate by HHS-FDA for passively transported drugs. It should be noted that all of these measurements assess the fraction absorbed (as opposed to the bioavailability, which can be reduced substantially by first-pass metabolism). 

With the difficulties associated with accurate estimation of permeability based only on physicochemical properties, a variety of methods of measuring permeability have been developed and used, among which are (l)cul-tured monolayer cell systems, such as Caco-2 or MDCK ( 2 diffusion cell systems that use small sections of intestinal mucosa between two chambers (3) in situ intestinal perfusion experiments performed in anesthetized animals such as rats and (4)intestinal perfusion studies performed in humans (40,54-62). All of these methods offer opportunities to study transport of drug across biological membranes under well-controlledconditions. Caco-2 mono-layer systems in particular have become increasingly commonly used in recent years and human intestinal perfusion methods are also becoming more commonly available. Correlations between Caco-2 permeability and absorption in humans have been developed in several laboratories (63-72). As shown in Fig. 

The test methods mostly follow British Standards, but some are more closely related to the ISO tests. Care must be taken to ensure that the correct sample size is u.sed. The determination of water absorption by diffusion is based on the Swiss Standard SIA 279 Part 5.07 [13] (see Section 2.6 below). Similarly the properties of extruded board are specified in BS 3837, Part 2, 1990 [14]. BS 3927, 1986 [15], specifies rigid phenolic foam for thermal insulation in the form of slabs and profiled sections. The material is classified as types A. B. and C. which differ principally in thermal conductivity, water vapor permeability and apparent water absorption. Thermal conductivity is measured by methods described in BS 4370, Part 2, Method 7 [16] or Appendix B of BS 874 [17]. ... 

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