Permeability testing

There is no uniformity as to how permeability testing is carried out in the pharmaceutical industry. This suggests that there may not be a great deal of difference in the effectiveness of the various experimental and computational permeability prediction methods. The people factor can easily be as (or even more) important than purely technical factors. The goal in a permeability assay or calculation is to influence chemistry behavior, that is to direct chemistry synthesis toward more permeable compounds. Thus the best assay or calculation may be the one that chemists (for whatever reason) believe and act on. This means that issues such as capacity, ease of use, ease of interpretation and internal credibility can be the deciding factor for effectiveness. As previously discussed, PSA calculations can be used as a permeability filter. PSA calculations are not very accurate if the compound is highly conformationally flexible the compound is multiply charged and if intramolecular H-bond 

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It should be noted also that the intercept is difficult to determine accurately because of large potential experimental error in observing the time of the start of filtration and the time-volume correspondence during the first moments when the filtration rate is high. The value of / calculated from the intercept may vaiy appreciably from test to test, and will almost always be different from the value measured with clean medium in a permeability test. 

Compression-Permeability Tests Instead of model leaf tests, compression-permeabihty experiments may be substituted with advantage for appreciably compressible sohds. As in the case of constant-rate filtratiou, a single run provides data equivalent to those obtained from a series of constant-pressure runs, but it avoids the data-treatment complexity of constant-rate tests. 

Figure 4.14 Permeability test celt. 1 - slurry vessel, 2 - valves, 3 - pipette, 4 - vessels, 5 - U-tuhe manometer (Mydlarz and Jones, 1989)...

Atterberg-limit tests determine the water content influence in defining liquid, plastic, semisolid and solid states of fine-grained soils. Permeability tests may be carried out in the laboratory or in the field. Such tests are used to determine the hydraulic conductivity coefficient k. ... 

IX lists the results of some of these experiments, comparing the nitrile materials with polyethylene, the most widely used plastic container material, and poly (vinyl chloride), which is being used for a number of food packaging applications. Note that in all instances there is an order of magnitude difference between the Lopac container and the other two. For flavorants, which are usually present in very low concentrations, this dilute solution test is probably more significant than a standard permeability test which only measures weight losses of the pure ingredient. 

The permeability tests for alkali metal ions in the aqueous solution were also conducted. When an aqueous salt solution moves to cell 2 through the membrane from cell 1, the apparent diffusion coefficient of the salt D can be deduced from a relationship among the cell volumes Vj and V2, the solution concentration cx and c2, the thickness of membrane, and time t6 . In Table 12, permeabilities of potassium chloride and sodium chloride through the 67 membrane prepared by the casting polymerization technique from the monomer solution in THF or DMSO are compared with each other and with that the permeability through Visking dialyzer tubing. The... 

D. Maurice and T. Singh, A permeability test for acute corneal toxicity, Toxicol. Lett., 31, 125 (1986). 

The CQA plan covers all components of landfill construction, including foundations, liners, dikes, LCRSs, and the final cover. According to the rule,13 U.S. EPA may also require field permeability testing of soils on a test fill constructed prior to construction of the landfill to verify that the final soil liner will meet the permeability standards of 10 7 cm/s. This requirement, however, will not preclude the use of laboratory permeability tests and other tests (correlated to the field permeability tests) to verify that the soil liner will, as installed, have a permeability of 10-7 cm/s. 

Underdrains are the most accurate in situ permeability testing devices because they measure exactly what comes out from the bottom of the liner. They are, however, slow to generate good data for low-permeability liners because they take a while to accumulate measurable flow. Also, underdrains must be put in during construction, so there are fewer underdrains in operation than there are other kinds of testing devices. They are highly recommended for new sites, however. 

Traditional permeability tests are time-consuming and subject to some uncertainties (4). In the present paper, we describe an automated technique for determining the filtrability of fairly dilute suspensions, which can give useful information, on the behaviour of polymeric flocculants. 

With regard to the most potent synthetic derivatives, FR 72112 (46g) showed significant effects on both rat hypotension and mouse vascular permeability tests. This compound inhibited PAF-induced hypotension by 51% (3 mg/kg, i.v.) and the increased vascular permeability by 40% (10 mg/kg, i.v.). However, FR 69049 ((44c) 10 mg/kg, i.v.) failed to inhibit PAF-induced hypotension in rats, suggesting the existence of at least two types of PAF receptor in vivo, that is, a platelet type and a vascular type. 

Gautheron, P.D., Dukic, M., Alix, D. and Sina, J.F. (1992). Bovine corneal opacity and permeability test An in vitro assay of ocular irritation. Fund. Appl. Toxicol. - Cut. Ocular Toxicol. 2 107-117. 

Ruth et alS4-7) have made measurements on the flow in a filter cake and have concluded that the resistance is somewhat greater than that indicated by equation 7.1. It was assumed that part of the pore space is rendered ineffective for the flow of filtrate because of the adsorption of ions on the surface of the particles. This is not borne out by Grace18 or by Hoffing and Lockhart(9) who determined the relation between flowrate and pressure difference, both by means of permeability tests on a fixed bed and by filtration tests using suspensions of quartz and diatomaceous earth. 

A compressibility-permeability test cell has been developed by Ruth(7) and Grace(8) for testing the behaviour of slurries under various conditions of filtration. A useful guide to the selection of a filter type based on slurry characteristics is given in Volume 6. 

At the beginning of the 1990s, the general acceptance of Caco-2 cell monolayers as a model of the small intestinal mucosa caused a significant push toward the field of permeability testing [2, 43], For detailed information about the Caco-2 cell line, the reader is referred to Chap. 8. As a consequence, the pharmaceutical community became more aware that permeation through intestinal epithelia is oftentimes more sophisticated than mere diffusion through a lipophilic membrane. 

Radial flow permeability testing apparatus. (Reprinted from J. R Feser et al. Journal of Power Sources 162 (2006) 1226-1231. With permission from Elsevier.)... 

Anti-implantation effect. Ethanol (50%) extract of the dried leaf, administered intragastrically to hamsters at a dose of 100 mg/kg, was active ° 5 Anti-inflammatory effect. EAM, administrated orally to rats, produced anti-inflammatory activity in the cotton pellet granuloma assay and in the carrageenin-induced pleurisy test. The effect was also produced in the peritoneal capillary permeability test in mice °° . 

Tarvainen et al. (2002) studied the film-forming ability of starch acetate (DS 2.8) and the effect of commotfly used plasticizers on the physical properties of starch acetate films. The properties were compared with ethylcellulose films. Mechanical studies, water vapor and drug permeability tests, and thermal analysis by differential scarming calorimetry (DSC) were used to characterize the film-forming ability of starch acetate and efficiency of tested plasticizers. Starch acetate films were foimd to be tougher and stronger than ethylcellulose films at the same plasticizer concentration. Also, in most cases, the water vapor permeability of starch acetate... 

Table 3. Permeability Test Results for Limestone SEA Mixes...

The permeability factor, K, has units of velocity and is inversely proportional to the viscosity of the gas. A permeability test is run by passing air... 

Temperature plays a part in all environmental tests but it was convenient to separate into Chapter 15 those tests which are particularly concerned with thermal resistance alone and to consider here the other types of environment to which rubbers may be exposed. This includes resistance to liquids and gases other than permeability tests (permeability is covered in Chapter 17). 

Functional tests intestinal permeability, tests of malabsorption (Lifschitz, 2005). 

Transport studies are performed at 24-well or 96-well formats. Cells grown in 175 cm2 flasks are moved to filter inserts and after 21 days of feeding and cultivation used in transport studies. The following method applies for use of 24-well filters of BD Falcon TM HTS 24-Multiwell Insert System. Alternatively, Costar 24-well filter systems could be used (non-coated, Transwell system). In many pharmaceutical companies cell permeability tests and feeding are performed with automatization equipment. 

Recently in some industrial labs blind probe test have been introduced 5 selected standards are analysed in permeability tests at different sites and results are compared (rating, recovery). The qualification and classification of the compounds to the criteria... 

There are advantages of cell culture models in permeability testing which should be exploited ade-... 

Examples of CACO-2 permeability tests are given in Artursson and Karlsson (1991), Artursson (1991), Hilgers et al. (1990), Stevenson et al. (1995), Walter et al. (1995), Wilson etal. (1990). Additionally, CACO-2 have been used in testing excipients (Saha et al. 2000) and applying simulated intestinal fluid (Ingels et al. 2004). 

In contrast to permeability tests, compounds are added not only to apical compartment (to determine flux A-B) but in an additional experiment to basolat-eral compartment (efflux B-A). As assay time 2 h is proposed. 

In contrast to permeability tests, compounds are added not only to apical compartment (to determine flux A-B) but in an additional experiment to baso-lateral compartment (efflux B-A). As assay time 2h is proposed. At the same time, an inhibitor is added and results of permeability and efflux assays compared to results obtained without inhibitor. Additionally, a selection of inhibitors covering different efflux transporters is used. After a preincubation period used in many studies (15 minutes for example) test compounds are added and flux/efflux studies performed. 

TABLE 1. Water permeability testing results of selected polymers using the ASTM E96E standard. 

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