Evaluation of the impact of multivalent metal ions on the permeation behavior of Dolutegravir sodium

Interactions between active pharmaceutical ingredients (APIs) and polyvalent cations are an important factor within drug absorption in the gastrointestinal tract. Dolutegravir sodium, as a second-generation integrase stand transfer inhibitor for the treatment of HIV was investigated regarding chelation with Al³⁺, Ca²⁺, Fe³⁺, Mg²⁺ and Zn²⁺ ions at three different molar ratios. Furthermore, the influence of drug–ion chelates on the permeability of the drug across two intestinal membrane models was analyzed. For this purpose, Caco-2 monolayer model and Ussing chamber technique utilizing freshly excited rat intestinal mucosa were chosen and a buffer system without additional Mg²⁺ and Ca²⁺ ions was tested regarding cell detachment. The addition of polyvalent cations in an equal molar ratio to the drug solution decreased the dissolved drug by at least 11%. An increased multivalent cation concentration in a ratio of 1:10 afforded an API drop in the solution of at least 88% with the exception of Mg²⁺. In particular, Dolutegravir sodium was chelated with iron ions to nearly 100%. Overall, the higher the amount of metal ions in the solution, the lower was the detected amount of the drug. The permeation experiments across the Caco-2 monolayer and the rat intestinal mucosa pointed out that the addition of AlCl₃, CaCl₂ and ZnCl₂ in a molar ratio of 10:1 to the drug led to significantly decreased drug permeation. According to these results the co-administration of Al³⁺, Ca²⁺ or Zn²⁺ as well as of supplementary medications containing these polyvalent ions is in case of oral Dolutegravir delivery not recommended.     

Performance analysis of shell‐and‐tube dehydrogenation module

This work investigates the operation of a small‐scale shell‐and‐tube‐shaped module for separating hydrogen from high‐pressure post‐shift syngas that would be produced in integrated gasification combined cycle plants. The separation occurs via permeation through palladium membranes that form the wall of the tubes. The main objective is to examine the effect of four design variables on the permeation performance. These variables are (i) flow rate, (ii) baffle spacing, (iii) inserting stinger tubes inside the permeate tubes, and (iv) switching the permeate stream from the tubes to the shell. The problem is treated by using three‐dimensional multi‐species computational fluid dynamic models, incorporating the Sievert's law for the permeation action. Quantitative assessment of the permeation and the incurred pressure drop was done by monitoring key integral parameters, such as two‐point efficiency, area‐based efficiency, and hydrogen recovery. The considered variables allow a wide spectrum of operation modes. This work thus gives the interested reader a generic guideline about the module design suitable for their specific aims. Copyright © 2016 John Wiley & Sons, Ltd.     

Hydrogen permeation through deformed and heat-treated Armco pure iron

ABSTRACT

The goal of this study is to obtain a deeper insight in the relation between hydrogen diffusion and hydrogen traps present in Armco pure iron. Cold deformation was applied to this material, which initially contained a limited amount of traps. The cold deformation was applied to increase the dislocation density and modify grain boundary characteristics. In this way, the hydrogen diffusivity decreased as the hydrogen trapping ability of the microstructure increased. A subsequent heat treatment allowed changing the density of microstructural defects again and consequently increased the hydrogen diffusion coefficient. In addition, studying blister formation showed that a higher degree of deformation caused more surface blisters, while recovery lowered the number of blisters. Electron backscatter diffraction characterisation provided the necessary input on the microstructural features and their evolution. Analysis of these samples allowed evaluating the correlation between hydrogen diffusion, blister formation and microstructural defects.

This paper is part of a thematic issue on Hydrogen in Metallic Alloys     

Complexes between linoleate and native or aggregated β-lactoglobulin: Interaction parameters and in vitro cytotoxic effect

The dairy protein β-lactoglobulin (βlg) is known to form a complex with fatty acids (FA). Due to industrial processing, βlg is often in its non-native form in food products, which can modify the FA/βlg complex properties. We investigated the interaction of bovine βlg, in selected structural forms (native βlg, a covalent dimer and as nanoparticles), with linoleate (C18:2). Using fluorescence and Isothermal Titration Calorimetry, linoleate was found to bind βlg at two different binding sites. Regardless of the structural state of βlg, association constants remained in the same order of magnitude. However, the stoichiometry increased up to 6-fold for nanoparticles, compared to that of native βlg. The impact of these structural changes on linoleate uptake in vitro was measured by cytotoxicity assays on Caco-2 cells. The order of cytotoxicity of linoleate was as follows: free > complexed to dimers > complexed to nanoparticles > complexed to native βlg. Therefore, the in vitro cytotoxicity of linoleate could be modulated by altering the state of βlg aggregation, which in turn affects its binding capacity to the FA.     

Preparation and evaluation of chitosan–itraconazole co-precipitated nanosuspension for ocular delivery

The purpose of the present study was to prepare itraconazole-loaded chitosan nanosuspension and evaluate it for ocular delivery. Itraconazole-loaded chitosan nanosuspension was prepared by controlled co-precipitation of chitosan and itraconazole from aqueous acetate solution using a combination of pH change and non-solvent addition. The co-precipitated suspension was evaluated for particle size, zeta-potential, entrapment efficiency and solubility study. It was observed that co-precipitation of itraconazole and chitosan from chitosan–lysine system in the presence of Poloxamer-188 as stabiliser provided nanosuspension of the smallest particle size with a 12-fold increase in aqueous saturation solubility of itraconazole and the fastest in vitro release. Transmission electron micrographs of the nanosuspension showed ovoid-shaped particles. A comparative evaluation of the itraconazole (1%, w/v) nanosuspension with commercial itraconazole suspension (1%, w/v) revealed a significantly higher percentage cumulative permeation of itraconazole across the isolated goat cornea from the nanosuspension dosage form as compared to the commercial suspension (P < 0.01).     

Precipitates and hydrogen permeation in HSLA steel produced by TMCP

Abstract

The precipitates and hydrogen permeation behaviour were investigated in high strength low alloy steel produced by thermomechanical controlled processing with air/water cooling after finishing rolling, and the water cooled specimens were further tempered at various temperatures. Two types of precipitates have been found in the specimens. One is TiN with the size ranging from 50 to 300 nm, and the other one is fine NbC. The cooling and tempering treatment conditions affect the precipitation behaviour of NbC particles in α-Fe, leading to the difference in hydrogen permeation. The apparent hydrogen diffusivity in the air cooled specimen is lower than that in the specimen quenched and subsequently tempered at 300°C when the charging current density is 10 mA cm^?2. Increasing the tempering temperature to 500°C leads to the decrease of apparent hydrogen diffusivity; but the value is still higher than that in the air cooled specimen. However, the apparent hydrogen diffusivity slightly increases with further increasing tempering temperature from 500 to 650°C.     

Preparation and characterization of PPSU/PBNPI blend membrane for hydrogen separation

Novel polymer blend membranes of poly(bisphenol A-co-4-nitrophthalic anhydride-co-1,3-phenylenediamine) (PBNPI) and polyphenylsulfone (PPSU) in different weight ratios were prepared by a solution casting technique with N-methyl-2-pyrrolidone (NMP) as solvent. The effects of blend polymer composition on the membrane structure and the H₂, CO₂ and CH₄ separation performance were investigated. The membranes appear macroscopically miscible but microscopically immiscible based on thin-film X-ray diffraction investigations. A remarkably and continuously enhanced permeability has been achieved for these gases with increasing PPSU content from 0 to 50%. The highest pure H₂, CO₂ and CH₄ permeability are, respectively, equal to 40.4, 34.1 and 8.0 barrer.     

Gas Permeation through Polydimethylsiloxane Membranes: Comparison of Three Model Combinations

The modeling of a gas mixture permeating through a polymeric membrane can be achieved by the combination of a mass transfer model with a thermodynamic model. In this study, three model combinations, i.e., the combination of Fick's law with Henry's law (F‐H), that of Fick's law with the UNIQUAC equation (F‐U), and that of the Maxwell‐Stefan equation with the UNIQUAC equation (MS‐U), were solved by iteration computer procedure to predict the separation performance of both binary and ternary gas mixtures permeating through a polydimethylsiloxane membrane. The predicted results were analyzed in detail and compared with experimental results. It was found that there are remarkable differences among the considered model combinations in predicting separation performance, and these differences tend to become larger with increasing solubility. Among the three considered model combinations, MS‐U gives the prediction closest to the experimental results. Its advantage over the other two model combinations should be due to the proper estimation of the permeate solubility by the UNIQUAC equation and the reasonable consideration of mass transfer resistance by the Maxwell‐Stefan equation.     

Momentum-Balance Aspects of Free-Settling Theory. I. Batch Thickening

Abstract

The theory of batch gravity thickening of an initially free-settling slurry is considered, taking into account the momentum-balance relationships for the system. It is concluded that graded-concentration zones which develop during the process must lie in the compression concentration range; retarding forces necessary to produce increase in concentration are not present in free settling.     

Selective Transport of Alkali and Alkaline Earth Metallic Ions through a Supported Liquid Membrane Containing Tripentyl Phosphate as a Carrier

Abstract

A selective transport system for alkali and alkaline earth metallic ions with a perchlorate ion as a pairing ion species through a supported liquid membrane (SLM) containing tripentyl phosphate (TPP) as a carrier is described. The SLM used is a porous polypropylene membrane impregnated with TPP solution in o-nitrophenyloctylether. The effects of the pairing ion species, the initial perchlorate concentration, and the TPP concentration on metallic ion transportability are examined under various experimental conditions. The permeation velocities of the metallic ions in the transport system followed the sequence Li⁺?Na⁺>K⁺>Mg²⁺; that is, a highly selective transport for Li⁺ ion was observed. Compared with the transport rates of alkali metallic ions, those of transition metallic ions such as Cu²⁺ and Fe³⁺ ions are very low. The permeation velocities of alkali and alkaline earth metallic ions through an SLM are dependent on the concentrations of perchlorate and TPP. Equations for the permeation velocities of Li⁺, Na⁺, K⁺, and Mg²⁺ ions through an SLM, based on two concentrations of perchlorate and TPP, are proposed.