Permeation experiments

The activity of absorbed hydrogen is a measure of the damage for a given material. H absorption can be easily investigated in H-permeation experiments [9]. Figure 2-20 shows experimental results for steel/aerated seawater. Significant H absorption occurs only in the range of cathodic overprotection (1/ < -0.8 V). 

In a permeation experiment, an HERO module with a membrane area of 200 m is used to remove a nickel salt from an electroplating wastewater. TTie feed to the module has a flowrate of 5 x IQ— m /s, a nickel-salt composition of 4,(X)0 ppm and an osmotic pressure of 2.5 atm. The average pressure difference across the membrane is 28 atm. The permeate is collected at atmospheric pressure. The results of the experiment indicate that the water recovery is 80% while the solute rejection is 95%. Evaluate the transport parameters Ay and (D2u/KS). 

Various anomalous diffusional behaviors have been observed and documented for both sorption and permeation experiments. Detailed discussions of these anomalies can be found elsewhere [12,35,36], Here only a brief summary of major findings is given. First, for the sorption anomaly, it has been observed that the reduced sorption curve has a distinctive thickness dependence. In this case, the reduced absorption and desorption curves obtained at various thick-... 

Fig. 2.7 Set-up of permeation experiment through organosilane monolayer immobilized on a porous glass plate. Reprinted with permission from [46], K. Ariga and Y. Okahata,J. Am. Chem. Soc., 1989, 77 7, 5618. 1989, American Chemical Society.

Various membrane types suitable for permeation experiments are listed below. More details are available in literature [66],... 

Reconstructed Human Epidermis Equivalents Because of the limited availability of human skin, reconstructed human epidermis equivalents are under investigation to serve as membranes in permeation experiments. A summary on these replacement tools has been recently published by Netzlaff et al. [92], First results of a German prevalidation study have shown the suitability of such bioengineered human epidermis equivalents in permeation studies [93],... 

As described previously in this chapter, efforts have been made to develop methods for quantification of skin permeability, validation of diffusion cell setups, and correlation of in vitro data with the in vivo situation. However, the average drug permeation experiment does not provide insight into the temporal and local disposition within the tissue, that is, the skin penetration. The following discussion will give an overview of methods tackling this kind of problem. 

Although more commonly used in permeation experiments for skin, there have been some research groups who use flow-through diffusion cells to assess... 

Recently it has been claimed that the tissue can be considered viable if the drug permeability does not change over the course of the experiment, and thus the actual permeability experiments themselves may provide insight into the viability of the tissue [109, 157], This method was employed in permeation experiments using porcine buccal mucosa, where the permeability of compounds was assessed in two consecutive permeability experiments to ensure the nature of the barrier was not compromised [111, 112]. While this demonstrates that the barrier nature of the tissue was unaltered between the permeation experiments, the tissue may have already undergone tissue death in the time between the excision and the commencement of the initial permeation experiment, and thus the permeability rate obtained in vitro may not be representative of the in vivo situation. Therefore, more studies assessing the dependence of the barrier nature of the buccal mucosa on tissue viability are... 

In our laboratory, the viability of excised porcine buccal mucosa was assessed using histological evaluation and a 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) biochemical assay which has previously been used in assessing the viability of excised buccal mucosa and cornea [49, 50], Histological evaluation of tissue demonstrated that the buccal epithelium appeared viable up to 9 h postmortem, and this was supported by the MTT biochemical assay, which indicated that viability was maintained for up to 12 h [80], Therefore, we recommend that all permeation experiments using porcine buccal mucosa be performed within 9-12 h of animal death. 

Since the use of human plasma as a model for skin esterases is debatable, the relevance of the biological results in Table 8.6 need validation as far as skin delivery is concerned. Indeed, permeation experiments across excised human skin showed that administration of prodrugs markedly improved the cutaneous delivery of nalidixic acid, with complete hydrolysis of the (acyl-oxy)methyl esters and significant, albeit incomplete, hydrolysis of the methyl and carbamoylmethyl esters [64],... 

The successful application of in vitro models of intestinal drug absorption depends on the ability of the in vitro model to mimic the relevant characteristics of the in vivo biological barrier. Most compounds are absorbed by passive transcellular diffusion. To undergo tran-scellular transport a molecule must cross the lipid bilayer of the apical and basolateral cell membranes. In recent years, there has been a widespread acceptance of a technique, artificial membrane permeation assay (PAMPA), to estimate intestinal permeability.117118 The principle of the PAMPA is that, diffusion across a lipid layer, mimics transepithelial permeation. Experiments are conducted by applying a drug solution on top of a lipid layer covering a filter that separates top (donor) and bottom (receiver) chambers. The rate of drug appearance in the bottom wells should reflect the diffusion across the lipid layer, and by extrapolation, across the epithelial cell layer. 

Such single molecule permeation experiments are used routinely. 

Results of such single-molecule permeation experiments, using the MV +/ Ru(bpy)3 pair (Fig. 16), and membranes with four different nanotubule i.d.s, are shown in Fig. 17. The slopes of these permeation curves define the fluxes of and Ru(bpy)3 across the membrane. A permeation selectivity coefficient (ai)t can be obtained by dividing the flux by the Ru(bpy)3 flux. 

The flux was determined by continuously monitoring the UV absorbance of the permeate solution by flowing the permeate through a UV detector, t The subscript i is for ideal and signifies that these coefficients were obtained via single-molecule permeation experiments (see, e.g.. Ref. 109). 

The smallest i.d. nanotubule membrane (Fig. 17D) showed a measurable flux for MV +, but the larger Ru(bpy)3 could not be detected in the permeate solution, even after a 2-week permeation experiment. 

A). To demonstrate this point, the rate and selectivity of transport across a conventional (Fig. 15A) and a bottleneck membrane were compared. Both membranes were able to cleanly separate from Ru(bpy)3 in the two-molecule permeation experiment (see below). Hence, these membranes showed comparable, excellent selectivity. However, as expected, the flux of across the bottleneck nanotubule membrane was dramatically higher than for the conventional nanotubule membrane (14 vs. 0.07 nmol hr cm ). 

Figure 18B shows the absorption spectrum for the feed solution used in the permeation experiment. Although both molecules are present in solution at the same concentration, the higher absorbance of the quinine nearly swamps out the 252-nm peak of the pyridine. Figure 18C shows the absorption spectrum of the permeate solution after a 72-hour permeation experiment. In spite of the higher absorbance of the quinine (larger molecule), only the peak for the pyridine (smaller molecule) is seen in this spectrum. Note, in particular, the complete absence of the very intense quinine band centered at 225 nm. Figure 18C shows that, to our ability to make the measurement, this bottleneck nanotubule membrane has filtered these two molecules on the basis of molecular size. 

The mechanism of diffusion of these permeant molecules in these membranes is an issue that must be explored in detail. We have shown [71] that the R = -C2H4-OH-derivatized nanotubules flood when immersed in water. In contrast, permeation experiments with inorganic salts suggest that the R = -C16H33 nanotubules do not flood with water. Hence, in these membranes the permeate molecule is partitioned into and diffuses through the Cig phase within the tubes. 

Permeability coefficients were calculated from the data obtained in the permeation experiments using the following equation ... 

Physicochemical tools can be categorized into two types membrane binding experiments and permeation experiments (Figure 6.4) [3]. The permeation barrier of a phospholipid bilayer is heterogeneous in nature and the rate-limiting barrier... 

Franz diffusion cells (FDC) remain the workhorse of all permeation experiments in transdermal studies. FDCs use the permeation of a solute, assessed by high pressure liquid chromatography (HPLC) or radiation, to evaluate the effect of penetration... 

Use of a surrogate end point that is quick and easy to obtain Permeation experiments using a radiolabeled, fluorescent, HPLC-detectable, or radio immuno assay/enzyme linked immuno sorbent assay-detectable marker necessitate the need of extensive sample handling and sample analysis. This accentuates the cost of sample analysis and overall time spent in characterizing the efficacy of formulations. Furthermore, current state of the art fluidics systems put a fundamental limit on the number of samples handled in a given time. 

FDC experiments typically use incubation times of 48 to 96 hours, thereby reducing the throughput of permeation experiments. Low incubation times favor high turnover frequencies for assay utilization. 

The composite membrane was subjected to the permeation experiments in which the volume flux of water and the rejection of polymer solutes, defined by... 

Figure 24 shows the rejections of polymer solutes, polyethylene glycols) (PEG) with monodispersed molecular weights. From Fig. 24, it is apparent that the composite membrane can find application for ultrafiltration. The molecular weight cut-off drastically decreased by more than 10 fold from the swollen state at 25 °C to the shrunken state at 45 °C. Thus the switching ability of the gel was demonstrated in the permeation experiments. 

Fig. 23. Swelling ratios of NIPA gel and volume fluxes across the composite membrane at various temperatures. Pressure difference between permeate and feed solutions in the permeation experiments is 10 [kg cm-2]...

Finally, we described the permeation characteristics of a thermosensitive gel supported on porous glass. The switch functional ability of the membrane was demonstrated in permeation experiments. It was pointed out that the change in the permeation characteristics resulted from that in the pore structure in the gel. 

The integral permeability coefficient P may be determined directly from permeation steady-state flux measurements or indirectly from sorption kinetic measurements 27 521 activity is usually replaced by gas concentration or pressure (unless the gas deviates substantially from ideal behaviour and it is desired to allow for this) and a<>, ax (p0, Pi) are the boundary high and low activities (pressures) respectively in a permeation experiment, or the final (initial) and initial (final) activities (pressures) respectively in an absorption (desorption) experiment. 

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