Permeation Amount Research Articles

Experimental evaluation of tritium permeation through stainless steel tubes of heat exchanger from primary to secondary water in ITER

Tritium permeation through heat exchanger from primary cooling water to secondary cooling water has been investigated experimentally with SS316L heat exchanger under simulated ITER (international thermonuclear experimental reactor) operation condition in order to establish the tritium permeation evaluation method through the heat exchanger. As the result, the permeation rate of aqueous tritium was found to be about three orders smaller than that of the gaseous tritium. Tritium permeation through the heat exchanger in ITER was then evaluated, and it was revealed that total tritium permeation amount based on obtained aqueous permeability was about one order less than that with the former method with the gaseous permeability and putting the permeation reduction factor as 1000. Evaluated tritium permeation amount into secondary water during 20 years was quite small, which could be considered as negligible from the safety viewpoint.

Transdermal iontophoresis of insulin: III. Influence of electronic parameters

Transdermal iontophoresis is a physical enhancement strategy primarily for charged molecules and offers a number of advantages for the delivery of peptides and proteins. The singular advantage of iontophoresis lies in the precise control of dose by manipulating the current protocol. The objective of the present investigation was to understand the role of electronic parameters on iontophoretic transport of large peptides using insulin as a model peptide. Ex vivo permeation experiments were conducted using excised rat skin and the influence of varying current strengths, duration, on/off ratios and switching iontophoresis on insulin permeation were studied. High performance liquid chromatography (HPLC), polyacrylamide gel electrophoresis (SDS-PAGE) and thin layer chromatography (TLC) were used to assess the electrochemical stability of insulin; while Fourier transform infra-red (FT-IR) spectroscopy and thermogravimetric analysis (TGA) were used to understand the biophysical changes in skin during iontophoresis. The permeation of insulin was found to increase as a function of current strength and duration of current application. Skin barrier integrity and electrochemical stability of insulin was dependent on the charge applied during iontophoresis. FT-IR spectroscopy and TGA studies showed that the skin hydration increased with increase in the charge applied and thus facilitated the transport of insulin. Periodic iontophoresis did not show any significant difference in insulin permeation compared with continuous current application; 1:1 on/off ratio resulted in higher amount of insulin permeation, while flux was highest with mixed duty cycle. Switching iontophoresis was useful in reducing the pH shift and in improving the electrochemical stability of insulin at pH 3.6 and 7.4, respectively. The electroosmotic flow was influenced by the pH of the donor medium, as well as by the electrode polarity during switching and non-switching iontophoresis. Overall, the study demonstrates the issues related to the optimization of electronic parameters for the iontophoretic delivery of a large peptide.

In vitro percutaneous absorption of cobalt.

To evaluate skin absorption of cobalt powder in an in vitro system. Experiments with volunteers show that cobalt powder can permeate through the skin, but there are no data with regard to the mechanism or the amount of permeation. Skin permeation was calculated by the Franz diffusion cell method with human skin. A physiological solution was used as receiving phase and the cobalt powder was dispersed in synthetic sweat. The amount of metal passing through the skin was analysed by electro-thermal atomic absorption spectrometry (ETAAS). Parallel polarographic analysis (differential pulse polarography-DPP) allowed evaluation of cobalt present as ions (Co(2+)) in donor and receiving phases. Measurements of cobalt skin content were also performed. Evaluation of metal in the receiving phase allowed us to demonstrate the permeation of cobalt through the skin. Steady-state flow of percutaneous cobalt permeation was calculated as 0.0123+/-0.0054 microg cm(-2) h(-1), with a lag time of 1.55+/-0.71 h. The experiments show that cobalt powder can pass through the skin when applied as a dispersion in synthetic sweat, oxidising metallic cobalt into ions, which permeate the skin. These experiments show for the first time how cobalt can permeate the skin.

In vitro skin permeation and retention of 5-aminolevulinic acid ester derivatives for photodynamic therapy

In photodynamic therapy (PDT), 5-aminiolevulinic acid (5-ALA) applied topically is converted, via the heme cycle, into protoporphyrin IX (PpIX), a photosensitizing agent, which upon excitation with light can induce tumor destruction. Due to its hydrophilic and zwitterionic characteristics, 5-ALA has limited penetration into the skin. More lipophilic 5-ALA ester derivatives are expected to cross stratum corneum more easily than 5-ALA. According to the determination of the partition coefficients of 5-ALA methyl, n-butyl, n-hexyl and n-octyl esters, these compounds showed an increased affinity to the SC, with 5-ALA hexyl ester and 5-ALA-octyl ester having the highest partition coefficients. Our in vitro skin permeation studies demonstrated an increased permeated amount for hexyl-ALA after 6 h of incubation, compared to other esters and 5-ALA. After 6 h, more 5-ALA-hexyl ester and -octyl ester were retained at viable epidermis and dermis than 5-ALA. According to these results, and considering that the conversion of 5-ALA into PpIX occurs preferentially in epidermis, it can be supposed that topical use of ester derivatives with longer chains (C 6 or C 8) is an interesting proposal to optimize topical 5-ALA-PDT

522 ステンレス鋼溶接部における水素透過現象の定量化に関する研究

It is necessary to reduce the hydrogen permeation through the welded joint in order to improve reliability of vacuum apparatus. For the base metal and the weld test specimens of stainless steel SUS304 of various thicknesses, hydrogen permeation quantification tests were carried out. As the result, it was revealed that the permeation quantity at the weld zone was about 4∿6 times of that of the base material. The relationship between the hydrogen permeation quantity and plate thickness was analyzed on the basis of diffusion theory, which showed that the hydrogen permeation flux was inversely proportional to the plate thickness, and this almost agreed with the experimental results.

312 低環境負荷プロセスによる超高分子量ポリエチレン多孔質膜の形成と特性評価

In this study, polymer system porous membrane was molded by extracting the soluble particle in boiling water, after it molded polyvinyl alcohol and water-soluble particle like the sugar by blending in UHMWPE. The following were carried out : Water permeability test of the porous film and the performance evaluation. It was possible that the water permeation quantity was made to change by UHMWPE and compounding ratio of the water-soluble particle. The water permeation quantity was affected by changing the particle size of the mixture. The water permeation quantity influences in the difference between the procedure in the case in which it is rolled, after the water-soluble particle is removed, and case in which it is removed after the rolling for the molding.

In vitro comparative studies of two marketed transdermal nicotine delivery systems: Nicopatch ® and Nicorette ®

The aim of this work was to compare in vitro the performances at delivering nicotine of two transdermal delivery system (TDS): Nicorette (8.3 mg/10 cm 2 nicotine content) and Nicopatch (17.5 mg/10 cm 2). Release profiles were obtained using the FDA paddle method, and skin permeation profiles using Franz-type diffusion cells. Using the first method, nicotine release followed the polymer matrix diffusion-controlled process, as suggested by the linear Q versus t 1/2 relationship. Cumulative amounts released from Nicopatch were twice the amounts released from Nicorette, but the released fractions were almost equal for both TDS (∼50%). Using diffusion cells, skin permeation rates were constant over the time: they were not significantly different between both TDS and close to in vivo claimed releases: Nicorette should be considered as more efficient at delivering nicotine through skin than Nicopatch. However, cumulative permeated amounts were overestimated, indicating that the actual diffusion surface area exceeded the effective diffusion surface area of the cells. Reducing the trimmed TDS surface area led not only to a reduction of the cumulative permeated amounts, but also to a reduction of the permeation rates. Therefore, the usefulness of the method to evaluate skin permeation parameters of TDS is questioned.

Transdermal delivery of nalbuphine and its prodrugs by electroporation

The aim of this study was to assess the effects of electroporation on transdermal permeation of nalbuphine (NA) and its prodrugs. The permeation characteristics were investigated under various electrical factors and skin barriers to elucidate the mechanisms involved in transdermal delivery of NA and its prodrugs by skin electroporation. The in vitro permeation studies were performed using side-by-side diffusion cells. The various electrical factors investigated were pulse voltage, pulse duration and pulse number; the different skin barriers studied were intact hairless mouse skin, stratum corneum (SC)-stripped skin, delipid skin as well as furry Wistar rat skin. The prodrugs were fully converted to parent drug after skin permeation. Application of electroporation significantly enhanced transdermal permeation of NA and its prodrugs. The enhancement ratios were highest for NA and the four prodrugs showed the similar permeability after electroporation. The permeation amounts of NA and its prodrugs may be increased by application of higher pulse voltage, pulse duration as well as pulse number. Various kinetics and mechanisms were observed for the permeation of the hydrophilic NA and lipophilic nalbuphine enanthate through different skin barriers by applying electroporation. This study demonstrated that electroporation may enhance and control transdermal permeation of NA and its prodrugs. The results also indicated that the physicochemical properties of prodrug had significant effects on kinetics as well as mechanisms of transdermal permeation by electroporation.

In vitro and in situ evidence for the contribution of Labrasol ® and Gelucire 44/14 on transport of cephalexin and cefoperazone by rat intestine

In vitro and in situ intestinal transport of β-lactam antibiotics in the presence of two novel pharmaceutical excipients, caprylocaproyl and lauroyl macrogolglycerides (Labrasol ® and Gelucire 44/14), is described. The objective was to compare the effects of both macrogolglycerides on the intestinal transport of cephalexin, a substrate of oligopeptide transporters, and cefoperazone, a non-substrate of them. The in vitro transport studies were performed using a sheet of rat jejunum mounted in Ussing-type diffusion chambers. The in situ studies used an isolated internal loop model in the rat. Labrasol ® and Gelucire 44/14 were used as the excipients at low concentrations (0.01–0.5%, w/v). The membrane permeability of both drugs was compared by apparent permeability coefficients ( P app) determined from changes in the amount of permeation vs. time in in vitro studies and by apparent absorptive clearance ( CL app) determined from changes in the steady state drug concentration of perfusate in in situ studies. The P app value of cephalexin increased with an increase in the concentration of Labrasol ® (0.05–0.5%) compared to the value without Labrasol ®. The enhancing effect of Labrasol ® on cephalexin transport was similarly observed in in situ studies, and when 0.5% Labrasol ® was used in the presence of glycyl- l-leucine or l-alanyl- l-alanine, 60 or 46% enhancement of the active transport of cephalexin by Labrasol ® was obtained. On the other hand, Gelucire 44/14 did not affect the P app and CL app of either drug. The different effects of the excipients on cephalexin transport were thought to be due to the influences of size parameters such as a polydispersity index and particle size, and the change in the short-circuit current of jejunum by the addition of the excipient.

Permeability characteristics of endocrine-disrupting chemicals using an in vitro cell culture model, Caco-2 cells.

The purpose of this study was to evaluate the permeability characteristics of endocrine disrupting chemicals utilizing epithelial monolayers of Caco-2 cells. The drugs tested in this study were bisphenol A (BPA), tert-octylphenol (tOP), tert-butylphenol (tBP), di(2-ethylhexyl)phthalate (DOP), dibutylphthalate (DBP), and butylbenzylphthalate (BBP), all of which are used in plastic materials. The Caco-2 cell line was grown on cell culture inserts with polyethylene terephthalate membranes, and Hank's balanced salt solution (HBSS, pH 7.4) was used for the transport experiments. The barrier properties were assessed by measuring transepithelial electrical resistance (TEER) using a volt ohmmeter, and transport of these endocrine disrupting chemicals was examined in both directions. The permeated amounts of these chemicals within 180 min in the apical to basolateral (A-to-B) and the basolateral to apical (B-to-A) directions without verapamil, a P-glycoprotein (P-gp) inhibitor, were in the rank order of tBP > tOP > BPA > DOP > DBP > BBP and BPA >> tBP > tOP > DOP > DBP > BBP, respectively. In the presence of 100 microM verapamil, the permeated amounts of BPA, tOP and tBP within 180 min in the B-to-A direction decreased by 12-, 2.6- and 3.1-fold, respectively. In the case of phthalate esters, the permeated amount of DOP within 180 min in the B-to-A direction decreased by 1.6-fold, while that of DBP and BBP showed no significant changes. The ratios of apparent permeability coefficient of B-to-A against A-to-B, P(app) ratios, for BPA, tOP and tBP were markedly decreased in the presence of 100 microM verapamil. These findings indicated that both BPA and alkyl phenols are substrates of the P-gp located in the apical side of Caco-2 cells, and suggested that the P-gp in the small intestine may act as an organic barrier against BPA and alkyl phenols.

Implantation driven permeation behavior of deuterium through pure tungsten

Implantation driven permeation behavior of deuterium through pure tungsten has been investigated to estimate the amount of tritium permeation through its barrier in a thermo-nuclear fusion device. The permeation experiments were performed on pure tungsten foil of 25 μm thickness under conditions of incident flux of 1.9×10 18–1.1×10 19 D +/m 2s, incident ion energy of 200–2000 eV, and specimen temperature of 512–660 K. As a result of this steady-state permeation experiment, the rate-determining process of deuterium permeation was found to be controlled by diffusion at both implanted and permeated sides. On the other hand, transient permeation was strongly affected by trap effect in the specimen. Simulation analysis using TMAP code on transient permeation behavior indicates the existence of a trap site with a trap energy of nearly 1eV and with a trap density of over several ten's ppm in tungsten.

Hydrogen permeability measurement through Pd, Ni and Fe membranes

An ultrahigh vacuum apparatus for the measurement of hydrogen gas permeation through metal membranes has been developed to perform studies in the ranges of low pressure and medium temperature. The sealing of the hydrogen gas at the specimen is done by gold O-rings which yield vacuum tightness. The hydrogen permeation is measured for pure Pd, Ni and Fe membranes over a pressure range of 0.1–100 mbar and a temperature range of 50–440°C. The results are compared with data in the literature. It shows that the permeation is exceedingly affected by the surface contamination on the specimens in the case of Pd. The contaminants are taken off from the Pd surface by short aging around 200–300°C in air. After cleaning the surface, the permeation amount increases and agrees well with the literature data. The activation enthalpies for permeation are (0.144±0.003), (0.600±0.003) and (0.382±0.004) eV for Pd, Ni and Fe, respectively, in the present investigation. For Ni and Fe, such a special treatment to clean the surface is not necessary.

Vitrification of Mouse Oocytes in Ethylene Glycol-Raffinose Solution: Effects of Preexposure to Ethylene Glycol or Raffinose on Oocyte Viability

We investigated the effects of preexposure to ethylene glycol (EG) or raffinose on the viability of vitrified mouse oocytes. Ovulated oocytes at the metaphase II stage were preexposed either to 2 M EG for 0, 2, or 5 min or to ascending concentrations (0.15 followed by 0.3 M ) of raffinose solution for 2, 5, or 10 min each (here referred to as 2-2, 5-5, and 10-10 min, respectively). The oocytes were then exposed to a vitrification solution (VS), 6 M EG + 0.3 M raffinose, for 0.5, 1, 2, or 5 min and then vitrified or immediately diluted. After warming, the developmental capacity of oocytes was determined after in vitro fertilization. Volume changes in oocytes during preexposures and exposure to the VS were also investigated. The results demonstrated that preexposure to 2 M EG allowed shorter exposure times of oocytes to the VS and that predehydration in raffinose solutions for 5-5, but not 2-2 or 10-10 min, allowed a wider range of exposure times to the VS. Experiments on volume change suggested that the optimum time of exposure to the VS depends on the amount of EG permeation after preexposure to 2 M EG or to raffinose solutions. Preexposures to 2 M EG or raffinose under optimized conditions increased the viability of vitrified-warmed oocytes compared to direct exposure to VS without preexposures.

Transfer of Radionuclides Across Skin Barriers of Animal Skin Models in Vitro

Radioactive skin contamination with radionuclides in ionic forms after the permeation across skin models was studied in vitro. Using animal skin models of 5-day-old rat and 9-day-old rat, either intact or stripped, it was found that besides the transepidermal also the transfolicular flux can be important. Stratum corneum was found to be the principal permeation barrier in all cases. The study of penetration — time profiles revealed that permeated amounts were proportional to time in the case of 137Cs+ and 60Co2+, but they showed a local maximum in the case of 147Pm3+.

Transport kinetics of leucine enkephalin across Caco-2 monolayers: Quantitative analysis for contribution of enzymatic and transport barrier

In this study, we determined the activities of four aminopeptidases such as aminopeptidase B (APB), M (APM), N (APN) and dipeptidylpeptidase IV (DPP IV) in Caco-2 cells and compared with those in the rat intestinal mucosae. The activities of APB, APM and APN appeared to be highest in rat small intestinal mucosa, while DPP IV activity was much higher in Caco-2 cells than that in the rat intestinal mucosa. Next the inhibitory effects of various protease inhibitors were examined in Caco-2 homogenate. Three tested inhibitors, bacitracin, amastatin and puromycin, effectively inhibited the activities of APM, APN and DPP IV except for APB. Further, we quantitatively evaluated the permeation and degradation properties of leucine enkephalin (Leu-Enk) in the presence or absence of inhibitors in Caco-2 monolayer system. Leu-Enk had a high degradation clearance (CLd) and a low permeation clearance (CLp) in Caco-2 monolayers. This finding indicates that the very rapid degradation of Leu-Enk on the apical side of Caco-2 monolayers was due to aminopeptidases. However, these protease inhibitors besides sodium glycocholate were able to reduce the CLd values markedly, thereby increasing the permeation amount of Leu-Enk across Caco-2 monolayers. In particular, amastatin significantly decreased the CLd value and increased the CLp value. This enhanced CLp value was further increased by the coadministration with an absorption enhancer, EDTA or laurylmaltoside. These findings are relevant to the oral administration of peptide dnigs and to developing an efficient oral delivery system.

Alkalinisation does not modify the effect of verapamil on myocardial Ca 2+ current

The effect of verapamil on L-type Ca 2+ current ( I Ca) was compared at external pH 7.4 and 8.5 in rat ventricular myocytes. Alkalinisation increases the fraction of uncharged molecules of verapamil (p K 8.75) and thereby facilitates membrane permeation of the drug. Verapamil (1 μM) reduced the amplitude of I Ca ( I Ca(peak)) by 36 ± 4% at pH 7.4 and by 40 ± 6% at pH 8.5, whereas alkalinisation from pH 7.4 to 8.5, without drug, increased I Ca(peak) by 12 ± 3%. It is suggested that the efficiency of verapamil is not influenced by the amount of protonation or membrane permeation.

Immunohistochemical localization of glutathione peroxidase, a lipid peroxides scavenger, in atherosclerotic lesions of human arteries

The localization of glutathione peroxidase (GSH-PO) in the human arteriosclerotic lesions was investigated by immunohistochemical methods. GSH-PO is an enzyme that effectively reduces lipid peroxides. It is also known that its synthesis is significantly increased by lipid peroxides, the substrate of the enzyme. Accordingly, the increased expression of GSH-PO would indicate the promotion of lipid peroxidation in the site. Immunohistochemistry for Apo-B protein, the major protein component of plasma low density lipoprotein (LDL), was also performed to show the amount of plasma LDL permeation and deposition on the arterial wall. Atheromatous plaques contained numerous GSH-PO positive cells with foamy cytoplasm, while normal arterial walls were almost devoid of GSH-PO positive cells. Immunoelectron microscopically, the GSH-PO reaction products were observed diffusely in the cytoplasm of these cells. The deposition of Apo-B was closely related to the localization of GSH-PO positive cells in the atheromatous lesions. These findings suggest that the lipid peroxidation that surpasses the protective actions of GSH-PO may cause foamy change of smooth muscle cells and macrophages to ultimately form atherosclerotic lesions.

Transdermal delivery of theophylline using an ethanol/panasate 800-ethylcellulose gel preparation.

A novel ethylcellulose gel preparation using an ethanol/panasate 800 (tricaprylin) (40/60) binary lipophilic vehicle was developed and applied to the transdermal delivery of theophylline. The in vitro skin permeability of theophylline across excised hairless mouse skin was improved by the use of this ethanol/panasate 800 (40/60) binary vehicle compared with either ethanol or panasate 800 as a single vehicle, and the addition of lauric acid as a permeation enhancer to the binary vehicle shortened the lag time and increased the permeated amount of theophylline up to 6 h (initial permeation amount). The in vitro permeability of theophylline from the ethanol/panasate 800 (40/60)-ethylcellulose gels decreased with an increase in the content of ethylcellulose in the gels. In the in vivo evaluation using abdominal rat skin, the ethanol/panasate 800 (40/60)-7% (w/w) ethylcellulose gel produced a good feature as a sustained-release preparation, with a relatively high bioavailability (BA) of theophylline, and dose dependency was observed.

Optimization of pressure-flow limits, strength, intraparticle transport and dynamic capacity by hydrogel solids content and bead size in cellulose immunosorbents

The design of existing beaded adsorbent materials for column-mode protein purification has emphasized the impact of diffusional transport phenomena upon adsorbent capacity. A design model is presented here that optimizes molecular accessibility of proteins relative to the mechanical stability at low operating pressures by manipulation of size and solids content for uncross-linked cellulose beads. Cellulose beads of several different sizes ranging from about 250 to 1000 μm diameter and having different solids contents were evaluated. Solids content of greater than about 9% cellulose greatly reduced the permeability of large proteins such as thyroglobulin and β-amylase into the beaded matrix at bead contacting times of about 5 and 50 s. Furthermore, the amount of permeation at 3% solids content by thyroglobulin at bead contacting times of about 5 s was about tenfold larger than predicted by diffusion models using the binary diffusivity in a purely aqueous continuum. The utility of a low solids content, large bead cellulose support was shown with immobilized IgG ( M r 155 kDa) capturing recombinant human Protein C ( M r 62 kDa). A 1000 μm diameter beaded cellulose immunosorbent having 3% solids content gave equivalent capacity to a 140 μm diameter beaded, cross-linked agarose support containing 4% solids. In contrast to the smaller diameter, cross-linked beaded agarose, the low solids content beaded cellulose benefitted from greater physical stability due to more optimal pressure-flow characteristics imparted by large bead size.

Diffusion in glassy polymer membrane considering time dependence of surface concentration.

We propose the equation of concentration and permeation amount calculated by Laplace transformation of Fick's second law under the boundary condition considering the variation of surface concentration and examined the equation for copoly(vinylidene cyanide-vinyl acetate) and polycarbonate membranes and various gases