Permeability method

The gas permeability coefficient P can be determined from the steady-state gas flow if the membrane thickness / is known, since 

Penneability measurements can be made using a simple experimental set-up, a schematic drawing of such a gas permeability test apparatus being given in figure IV - 35. 

The cell containing a homogeneous membrane of known thickness is pressurised with a chosen gas. The extent of gas permeation through the membrane is measured by means of a mass flow meter or by a soap bubble meter. More sophisticated set-ups employ a calibrated volume connected to the permeate side with the small pressure increase in the calibrated volume being measured with a pressure transducer. The gas permeability or nermeabilin- coefficient P can be detennined from the steady-state gas flow if the membrane thickness t is known, since 

The liquid permeadng through the membrane is evaporated on the downstream side and collected in the condenser which is cooled with liquid nitrogen or another cooling agent. The amount of liquid can be determined simply by weighing. 

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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... 

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. 

Even in applications other than dewatering, permeability methods are quite often used to assess the performance of polymeric flocculants, since, in principle, they can give a very sensitive indication of the state of aggregation of particles and are useful in locating optimum polymer concentrations. 

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). 

Kwong, J. N. S., Adams, J. T., Johnson, J. F. and Piret, E. L. Chem. Eng. Prog. 45 (1949) 508. Energy-new surface relationship in crushing. I. Application of permeability methods to an investigation of the crushing of some brittle solids. 

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. 

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. 

The permeability class of a drug substance can be determined in human subjects using mass balance, absolute BA, or intestinal perfusion approaches. Recommended methods not involving human subjects include in vivo or in situ intestinal perfusion in a suitable animal model (e.g., rats), and/or in vitro permeability methods using excised intestinal tissues, or monolayers of suitable epithelial cells. In many cases, a single method may be sufficient (e.g., when the absolute BA is 90%... 

For direct permeability methods, infonnation supporting the suitability of a selected method that encompasses a description of the study method, criteria for selection of human subjects, animals, or epithelial cell line, drug concentrations in the donor fluid, description of the analytical method, method used to calculate extent of absorption or permeability, and where appropriate, infonnation on efflux potential (e.g., bidirectional transport data)... 

This attachment includes model drugs suggested for use in establishing suitability of a permeability method as described in section III. The permeability of these compounds was determined based on data available to the FDA. Potential internal standards (IS) and efflux, pump substrates (ES) are also identified. 

Carman s Gas Permeability Method. A gas or a wetting liquid is made to flow through the porous... 

KMn04 method. Sieve residue on 16900 sieve (DIN 4188, aperture 45 pm). cAir permeability method. 

Since some of the published pressure drop correlations can differ by an order of magnitude, it is best to verify the relationship with actual data before designing a reactor. Other approaches to two-phase pressure drop include the relative permeability method of Saez and Car-bonell [AIChE J. 31(1) 52-62 (1985)]. 

With regard to the standardization of the technique used in applying this equation, see Report on Air-Permeability Method for Determining Fineness of Cement A.S.T.M. Bulletin, No. 118 October 1942, pp. 31-36. 

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. 

The following model describes hydrogen transfer in metal membrane with the protective coat (stainless steel covered by TiN) for small pressures in the case of the permeability method ... 

The estimation of parameters D, b, s, a, a2 in model (11) - (17) of the hydrogen transfer in stainless steel was made by the identification algorithm based on the Fourier series. The detailed description of the algorithm is in [3, 4]. The experimental data got by the concentration pulses method were used for identification. In addition the estimations of s, X = Db1/2 were received by isotherms for the permeability method [3, 4]. Below we describe the identification algorithm based on the Fourier series. 

The particle size and surface area distributions of pharmaceutical powders can be obtained by microcomputerized mercury porosimetry. Mercury porosimetry gives the volume of the pores of a powder, which is penetrated by mercury at each successive pressure the pore volume is converted into a pore size distribution. Two other methods, adsorption and air permeability, are also available that permit direct calculation of surface area. In the adsorption method, the amount of a gas or liquid solute that is adsorbed onto the sample of powder to form a monolayer is a direct function of the surface area of the sample. The air permeability method depends on the fact that the rate at which a gas or liquid permeates a bed of powder is related, among other factors, to the surface area exposed to the permeant. The determination of surface area is well described by the BET (Brunauer, Emmett, and Teller) equation. 

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. 

All of the permeability methods are based on the Kozeny-Carman equation, which is used to calculate a surface area of a packed powder bed from its permeability. The Kozeny-Carman equation is expressed as [16]... 

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. 

The specific surface area, like the PSD, is thus a quality whose value depends on how it is defined, and is liable to be affected by any pretreatment or conditions affecting the degree of flocculation. In practice, air permeability methods are widely used. Typical values are 300-350 m kg for modern ordinary Portland cements and 400-450 m kg " for rapidhardening Portland cements. 

In situ methods involve the external perfusion of an isolated segment of intestinal tissne." The rat has been shown to be an excellent model for human intestinal permeability." One of the principle advantages of the in situ method is that the intact rat intestinal tissne maintains a normal complement of influx and efQux transporters. Cephalosporins and beta-lactam antibiotics are known to be absorbed by oligopeptide transporters in the GI tract. The rat in situ permeability method was used to determine the saturable Michaelis-Menten-type kinetics for this class of drug molecules. In like fashion, the permeabilities of thymidine anti-viral drugs, like AZT, involving the nncleoside transporter were determined in situ. ... 

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. 

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