The Prediction of the Dissolution Rate Constant by Mixing Rules: The Study of Acetaminophen Batches

The purpose of this article is to promote two simple and scalable methods to accelerate the formulation development of formulated granules using acetaminophen as a model system. In method I, formulated granules made from the batch of small particle–sized acetaminophen (1) by ball milling the batch of large particle–sized acetaminophen (2), and the mixture of the two batches at equal weights (mix) gave the dissolution rate constants (k) of k₁?=?0.43 ± 0.15 minutes^?1, k₂?=?0.18 ± 0.01 minutes^?1, and k_mix?=?0.30 ± 0.03 minutes^?1 for 75 wt percent formulation; k₁?=?0.75 ± 0.01 minutes^?1, k₂?=?0.18 ± 0.01 minutes^?1, and k_mix?=?0.34 ± 0.03 minutes^?1 for 62 wt percent formulation; and k₁?=?0.28 ± 0.01 minutes^?1, k₂?=?0.16 ± 0.01 minutes^?1, and k_mix?=?0.22 ± 0.02 minutes^?1 for 30 wt percent formulation. In method II, the mixture of the formulated granules produced by mixing the formulated granules from the two batches at equal weights gave dissolution rate constants of k_mix?=?0.30 ± 0.03 minutes^?1, 0.30 ± 0.02 minutes^?1, and 0.22 ± 0.01 minutes^?1 for 75 wt percent, 62 wt percent, and 30 wt percent formulations, respectively. After fitting the three data points of k₁, k₂, and k_mix to the 10 mixing rules in materials science—series mixing rule, Hashin and Shtrikman upper bound, logarithmic mixing, Looyenga mixing rule, effective media approximation (EMA), three-point lower bound, Torquato approximation, three-point upper bound, Maxwell mixing rule, and parallel mixing rule—we found that the selection of the best suited mixing rules based on k₁, k₂, and k_mix was solely dependent on the formulations under a given operating condition and regardless of whether the system was a powder mixture or a granular mixture. The values of k₁, k₂, and k_mix in both the 75 wt percent and 30 wt percent formulations were enveloped by the parallel mixing rule and Maxwell mixing rule, whereas the values of k₁, k₂, and k_mix for the 62 wt percent formulation were encompassed by the logarithmic mixing rule, Hashin and Shtrikman upper bound, and the series mixing rule. Apparently, the best suited mixing rules could be used to predict the right proportions of either the powder mixture (Method I) or the granular mixture (Method II) for obtaining any other desired dissolution rate constant, k_mix, whose value fell in between the values of k₁ and k₂.     

Characterizing the discoloration of methylene blue in Fe/H2O systems

Methylene blue (MB) was used as a model molecule to characterize the aqueous reactivity of metallic iron in Fe⁰/H₂O systems. Likely discoloration mechanisms under used experimental conditions are: (i) adsorption onto Fe⁰ and Fe⁰ corrosion products (CP), (ii) co-precipitation with in situ generated iron CP, (iii) reduction to colorless leukomethylene blue (LMB). MB mineralization (oxidation to CO₂) is not expected. The kinetics of MB discoloration by Fe⁰, Fe₂O₃, Fe₃O₄, MnO₂, and granular activated carbon were investigated in assay tubes under mechanically non-disturbed conditions. The evolution of MB discoloration was monitored spectrophotometrically. The effect of availability of CP, Fe⁰ source, shaking rate, initial pH value, and chemical properties of the solution were studied. The results present evidence supporting co-precipitation of MB with in situ generated iron CP as main discoloration mechanism. Under high shaking intensities (>150 min⁻¹), increased CP generation yields a brownish solution which disturbed MB determination, showing that a too high shear stress induced the suspension of in situ generated corrosion products. The present study clearly demonstrates that comparing results from various sources is difficult even when the results are achieved under seemingly similar conditions. The appeal for an unified experimental procedure for the investigation of processes in Fe⁰/H₂O systems is reiterated.     

Influence of indigenous and added iron on copper extraction from soil

Experimental tests of copper leaching from a low permeability soil are presented and discussed. The objective of the experiments was to investigate the influence of indigenous and added iron in the soil towards copper mobilization. Metals’ leaching was performed by flushing (column tests) or washing (batch tests) the soil with an aqueous solution of ethylenediaminetetraacetic acid, EDTA. An excess of EDTA was used in flushing tests (up to a EDTA:Cu molar ratio of about 26.2:1), while, in washing tests, the investigated EDTA vs. copper molar ratios were in the range between 1 (equimolar tests) and 8.Copper extraction yield in flushing tests (up to about 85%) was found to depend upon contact time between the soil and the leaching solution and the characteristics of the conditioning solution. The saturation of the soil with a NaNO₃ solution before the treatment, favoured the flushing process reducing the time of percolation, but resulted in a lower metal extraction during the following percolation of EDTA.The indigenous iron was competitive with copper to form EDTA complexes only when it was present in the organic and oxides–hydroxides fractions. Artificial iron addition to the soil resulted in an increase of both the exchangeable iron and the iron bonded to the organic fraction of the soil, thus increasing the overall amount of iron available to extraction.In both batch and continuous tests, the mechanism of copper extraction was found to involve the former dissolution of metal salts, that lead to an initial high concentration of both copper and selected competitive cations (essentially Ca²⁺), and the following EDTA exchange reaction between calcium and copper complexes. The initial metal salts dissolution was found to be pH-dependant.     

Dispersion and reaction of TiB2 in liquid iron alloys

Abstract

The degree of reaction and dispersion achieved when TiB₂ powders are melted in contact with liquid iron based alloys has been assessed via a levitation dispersion test which had been developed earlier. Both Fe₂B and TiC were observed to form as a result of dissolution and reaction of TiB₂. The formation of TiC occurs during the reaction of commercial grade TiB₂ with liquid iron alloys containing as little as 0·08 wt-%C. The reaction of high purity TiB₂ with liquid iron alloys containing 0·24 wt-%C does not however lead to TiC formation. The formation of Fe₂B was observed for all conditions tested, owing to the effectively zero solubility of boron in solid iron. The TiB₂ remaining after dissolution and reaction was found to produce relatively good dispersions in the iron matrix and therefore additions of TiB₂ to liquid iron alloys may provide a means of producing Fe–TiB₂ composite materials. However, the brittle properties of Fe₂B will mean that, whereas such materials may be very hard, they are likely to lack toughness.

MST/1477     

Preparation and characterization of bio-functionalized iron oxide nanoparticles for biomedical application

Amine modified iron oxide (Fe₃O₄) nanoparticles were synthesized by thermal decomposition method and were further used to bio-functionalize by grafting of N-hydroxysuccinimide (NHS) ester of folate and ethylenediaminetetraacetate (EDTA). Fe₃O₄ nanoparticles of ~ 22 nm were confirmed from X-ray diffraction (XRD) and transmission electron microscopy (TEM) studies. FT-IR studies indicated two bands at 1515 cm^− 1and 1646 cm^− 1, which can be attributed to carboxylic group and the amide linkage respectively, revealing the conjugation of folate with Fe₃O₄. The conjugation of the chelating agent showed strong C=O stretch and Fe-O vibrations at 1647 and 588 cm^− 1 respectively. The value of saturation magnetization for Fe₃O₄ nanoparticles was found to be 88 emu/g, which further reduced to 18 and 32% upon functionalization with EDTA and NHS ester folate, respectively. These amine modified Fe₃O₄ nanoparticles can also be functionalized with other bifunctional chelators, such as amino acids based diethylene triamine pentaacetic acid (DTPA), and thus find potential applications in radio-labeling, biosensors and cancer detection, etc.     

Iron species in fusion-cast,glassy-phase-containing corundum materials; EPR and susceptibility analyses

By means of EPR, susceptibility, EMP, light-microscopic, thermal and chemical methods the influence of production conditions and subsequent treatments on glassy-phase-containing corundum materials were studied. Melting of the system (Al₂O₃, SiO₂, Na₂O, Fe₃O₄) under reductive conditions leads to a reduction of Fe³⁺ species contained to Fe²⁺ and even to Fe⁰ clusters with ferromagnetic behaviour. Both species markedly influence the mechanical properties of the material by increase of their volumes in consequence of oxidation in subsequent thermal processes. The following model with regard to the localization of the iron species in the system ensues: Fe(III) in corundum, Fe₂O₃, Fe₃O₄ and (scarcely) in the glassy phase; Fe(II) in the glassy phase, FeAl₂O₄ (hercynite) as a solid solution in corundum, and Fe₃O₄; (Fe⁰) clusters in corundum. It is therefore not surprising that grinding of the compact material considerably alters the magnetic properties of the samples.     

Perchlorate removal in Fe0/H2O systems: Impact of oxygen availability and UV radiation

In this study, the removal of perchlorate (0.016 mM ) using Fe⁰-only (325 mesh, 10 g L⁻¹) and Fe⁰ (10 g L⁻¹) with UV (254 nm) reactions were investigated under oxic and anoxic conditions (nitrogen purging). Under anoxic conditions, only 2% and 5.6% of perchlorate was removed in Fe⁰-only and Fe⁰/UV reactions, respectively, in a 12 h period. However, under oxic conditions, perchlorate was removed completely in the Fe⁰-only reaction, and reduced by 40% in the Fe⁰/UV reaction, within 9 h. The pseudo-first-order rate constant (k₁) was 1.63 × 10⁻³ h⁻¹ in Fe⁰-only and 4.94 × 10⁻³ h⁻¹ in Fe⁰/UV reaction under anoxic conditions. Under oxic conditions, k₁ was 776.9 × 10⁻³ h⁻¹ in Fe⁰-only reaction and 35.1 × 10⁻³ h⁻¹ in the Fe⁰/UV reaction, respectively. The chlorine in perchlorate was recovered as chloride ion in Fe⁰-only and Fe⁰/UV reactions, but lower recovery of chloride under oxic conditions might due to the adsorption/co-precipitation of chloride ion with the iron oxides. The removal of perchlorate in Fe⁰/UV reaction under oxic conditions increased in the presence of methanol (73%, 9 h), a radical scavenger, indicating that OH radical can inhibit the removal of perchlorate. The removal of perchlorate by Fe⁰-only reaction under oxic condition was highest at neutral pH. Application of the Langmuir-Hinshelwood model indicated that removal of perchlorate was accelerated by adsorption/co-precipitation reactions onto iron oxides and subsequent removal of perchlorate during further oxidation of Fe⁰. The results imply that oxic conditions are essential for more efficient removal of perchlorate in Fe⁰/H₂O system.     

Microanalysis of the surface in glass-ceramics obtained from muscovite-amblygonite

A new family of glass-ceramics obtained from muscovite-amblygonite mixtures showing a schiller effect or reflecting surface has been obtained. This effect has not been observed in the bulk material. The raw materials contain about 1% iron as Fe²¹. In order to elucidate the correlation between surface structure and/or composition and the schiller surface effect, several surface analysis methods, (ESCA, RBS, EPR and reflection Mössbauer spectroscopy) have been used. It seems that a solid solution of Fe³¹ in the spodumene crystal lattice precipitated from the surface is related to the reflecting effect, which can be controlled by solution of iron oxides in the-spodumene solid solution.     

Dissolution kinetics of iron in liquid zinc

In hot dip galvanizing, steel strip is coated by immersion in a bath of molten zinc. The principal reactions that occur at the steel/liquid zinc interface are (1) dissolution of iron and (2) nucleation and growth of intermetallic compounds. In order to improve the management of industrial galvanizing baths, it is essential to evaluate the flux of dissolved iron that diffuses into the bath from the sheet. For this purpose, a rotating disk device has been developed to study the dissolution and diffusion of iron in pure liquid zinc at the temperature usually employed in galvanizing baths (465°C). Since the dissolution reaction is controlled by diffusion under these conditions, the diffusion coefficient of iron in liquid zinc has been measured and found to be: D _Fe ^Zn(L) = (9.8 ± 0.1) × 10^–10 m²·s^–1     

Structural and magnetic properties of strontium–borate glasses containing iron ions

Glasses of the xFe₂O₃·(100 − x)[B₂O₃·SrO] system, with 0 ≤ x ≤ 30 mol%, were studied by EPR and magnetic susceptibility measurements. EPR spectroscopy and magnetic susceptibility measurements show that the Fe³⁺ ions are localized in sites of distorted octahedral symmetry and in clustered formations containing both Fe³⁺ and Fe²⁺ ions. Dipolar and superexchange interactions involving iron ions were revealed depending on the iron content of the sample.     

Stagewise behavior of the electrochemical dissolution of a loaded metal under the conditions of its local interaction with corrosive media

We show that the process of local electrochemical dissolution of iron of loaded low-carbon 20 steel (σ_0.2=270 MPa) in a corrosive medium (3% aqueous NaCl solution, pH 6.9) is multistage. The characteristics of the process depend on the form of the surface interacting with the corrosive medium. The investigated cases are arranged in the following order according to the rate of dissolution of the metal: a smooth surface, a stress concentrator, and a stress concentrator with a short crack-like defect. We propose and detect the corresponding electrochemical reactions and their sequence (stagewise behavior) realized in the course of the process. The electrochemical parameters of local anodic dissolution of the metal at tips of corrosion cracks of various depths and openings are determined. On the basis of these results, we suggest an autocatalytic mechanism of dissolution of the metal in which Fe²⁺ ions are autocatalytic particles. We demonstrate agreement between the results calculated by using classical electrochemical equations for the kinetics of electrode processes and experimental data obtained in corrosive media with various concentrations of Fe²⁺ ions in the rangeC _Fe ²⁺=1.0·10^-5-2.0·10^-1. This means that the indicated mechanism can be realized at the tip of a corrosion crack. Karpenko Physicomechanical Institute, Ukrainian Academy of Sciences, L'viv. Translated from Fizyko-Khimichna Mekhanika Materialiv, Vol. 34, No. 2, pp. 18–28, March–April, 1998.     

Bulk and surface structures of iron doped zirconium oxide systems: Influence of preparation method

Three different Fe-Zr oxide systems were prepared using firstly classical impregnation of iron nitrates on calcined ZrO₂ (Fe_x/ZrO₂, x represents Fe/Zr ratio = 0.01 and 0.11), secondly impregnation of iron nitrates on dried zirconium hydroxide ZrO(OH)₂ (Fe_x/ZrO(OH)₂) and finally hydrolysis of aqueous suspension of iron and zirconium salts to coprecipitate iron and zirconium hydroxides (Fe_x-Zr). Thermal decomposition study of dried samples evidenced a delay in the temperature crystallization of zirconia for Fe_x-Zr and Fe_x/ZrO(OH)₂, the more the iron content in the sample, the more important the delay. For these samples, the formation and the stabilization of different phases were evidenced by several characterization techniques : X-Ray Diffraction (XRD), Raman spectroscopy and Electron Paramagnetic Resonance (EPR).The interaction of iron species with zirconia was different in accordance with different preparations. A bulk dispersion of the coprecipitated sample was observed and as a consequence Zr^{3 +} defects in the solid were not produced. In the case of Fe_x/ZrO₂ sample, production of surface Zr^{3 +} ions was established at low temperature of calcination (up to 600^∘C) and explained by the reaction of NO₃⁻ with Zr^{4 +} on the zirconia surface. However such interaction did not occur for Fe_x/ZrO(OH)₂ since a low dispersion of iron species was observed by X-ray Photoelectron Spectroscopy (XPS), deposited phase (Fe₂O₃) forming preferentially blocks. Temperature Programmed Reduction (TPR) showed that the reduction of small particles of Fe₂O₃ and bulk Fe₂O₃ present in the impregnated samples was easier than that of iron species well dispersed in the bulk of the coprecipitated solid.     

Investigation of ESR on Fe Ions in Kondo Dielectric SmB<Subscript>6</Subscript>

Electron spin resonance (ESR) was studied in Kondo dielectric SmB₆ doped with 1 at.% of Fe. The ESR measurements were performed on single crystal of SmB₆ in the temperature range 10–300 K. We have observed two resonance lines with g-factors of 2.25 and 3.0 indicating the presence of iron in Fe⁰ and Fe²⁺ states. Ferromagnetic ordering of iron ions is observed below the Curie point at 100 K, which can be attributed to indirect exchange of impurity ions via polarization of the matrix (a mechanism similar to that found in PdFe alloys). However, the estimate of the intensity of this indirect exchange demonstrate nearly three orders of magnitude enhancement compared to its value in PdFe caused by extraordinary high density of states in a narrow f-band characteristic of material with the fluctuating valence.     

Study of the corrosion layer on iron obtained in solutions of water-polyethylene glycol (PEG 400)-sodium phosphate

The iron behaviour in phosphate/water/polyethylene glycol (PEG) was studied in-situ and ex-situ by spectrometry Raman, ESCA spectroscopy, X-ray diffraction, Auger spectroscopy were used as surface analysis methods. It changes with phosphate concentration. At low phosphate concentration (5 × 10^–4 M-10^–3 M-5 × 10^–3 M), iron is corroded. The thin corrosion layer is a mixture of iron oxides (-Fe₂O₃, Fe₃O₄) and iron phosphate(Fe₃(PO₄)₂, 8H₂O). At high phosphate concentration (10^–2 M-5 × 10^–2 M), the iron is protected. The protection could be due to an heterogenous layer containing PEG 400 and phosphates.     

Synthesis and characterization of Fe3+-modified PLZT ferroelectrics

Fe³⁺-modified nanocrystalline PLZT, i.e., Pb_0.92[La_1–z Fe _z ]_0.08[Zr_0.60Ti_0.40]_0.98O₃ (PLFZT) (z=0.0, 0.3, 0.6, 0.9, 1) materials were synthesized by a high-temperature solid-state reaction technique. X-ray studies of the compounds confirmed the formation of single-phase, ultrafine (nano-sized) and homogeneous materials. Microstructural scanning electron microscopy (SEM) study shows the uniform distribution of smaller grains on the surface of the samples. Detailed dielectric studies of the compounds as a function of temperature (30–450 °C) show that the broadening of the permittivity peak and transition temperature depends on Fe³⁺-ion concentration. Analysis of diffuseness () of the broadened dielectric peaks of the materials gave its value between 1 and 2, indicating the different degrees of substitutional disorder in the system. The increase in Fe³⁺-substitution at the La-site of PLZT shows many interesting and unusual dielectric relaxor behaviors of the compounds. The transition temperature T _c of PLZT (8/60/40) ferroelectric shifts towards a higher temperature region on increasing Fe³⁺ concentration. The variation of d.c. and a.c. electrical conductivity of the material with temperature shows its semiconducting behavior; and hence the materials can be used for some electronic devices.     

Synthesis of Uniquely Structured Yolk–Shell Metal Oxide Microspheres Filled with Nitrogen‐Doped Graphitic Carbon with Excellent Li–Ion Storage Performance

Novel structured composite microspheres of metal oxide and nitrogen‐doped graphitic carbon (NGC) have been developed as efficient anode materials for lithium‐ion batteries. A new strategy is first applied to a one‐pot preparation of composite (FeO_x‐NGC/Y) microspheres via spray pyrolysis. The FeO_x‐NGC/Y composite microspheres have a yolk–shell structure based on the iron oxide material. The void space of the yolk–shell microsphere is filled with NGC. Dicyandiamide additive plays a key role in the formation of the FeO_x‐NGC/Y composite microspheres by inducing Ostwald ripening to form a yolk–shell structure based on the iron oxide material. The FeO_x‐NGC/Y composite microspheres with the mixed crystal structure of rock salt FeO and spinel Fe₃O₄ phases show highly superior lithium‐ion storage performances compared to the dense‐structured FeO_x microspheres with and without carbon material. The discharge capacities of the FeO_x‐NGC/Y microspheres for the 1st and 1000th cycle at 1 A g^?1 are 1423 and 1071 mAh g^?1, respectively. The microspheres have a reversible discharge capacity of 598 mAh g^?1 at an extremely high current density of 10 A g^?1. Furthermore, the strategy described in this study is generally applied to multicomponent metal oxide–carbon composite microspheres with yolk–shell structures based on metal oxide materials.     

Processing of Nimesulide-PEG 400-PG-PVP Solid Dispersions: Preparation,Characterization, and In Vitro Dissolution

Abstract

The objective of this investigation was to study the influence of dissolution enhancers such as polyethylene glycol 400, propylene glycol, polyvinylpyrrolidone K30, sodium lauryl sulfate, and Tween 80 on in vitro dissolution of a model active pharmaceutical material—nimesulide. Preliminary studies were conducted using a physical blend of nimesulide, and the adjuvants and solid dispersions were prepared using solvent evaporation and cogrinding methods. Aqueous solution of adjuvants was first triturated with nimesulide, followed by mixing with lactose and microcrystalline cellulose, and finally water was evaporated under vacuum in a cogrinding method. A 3³ factorial design was adopted in a cogrinding method using the concentration of polyethylene glycol 400, propylene glycol, and polyvinylpyrrolidone K30 as independent variables. Tween 80 and sodium lauryl sulfate were added in all the batches. Full and reduced models were evolved for different dependent variables. The reduced models were validated using two checkpoints. Angle of repose <35°, percentage of drug released in 30 min (Q₃₀)>40%, 45 min (Q₄₅)>50%, and 120 min (Q₁₂₀)>60% were used as constraints for the selection of an optimized batch. Contour plots are presented for the selected dependent variables. Polyvinylpyrrolidone was found to be more effective in increasing the drug dissolution, compared with polyethylene glycol 400 and propylene glycol. The granule flow was adversely affected when high levels of liquid adjuvants were used in formulations. Wettability study was conducted to measure wetting time for pure drug and the optimized batch. Improved drug dissolution was attributed to improved wetting and the solubilizing effect of adjuvants from the pseudosolid dispersions of nimesulide. Significant improvement in drug dissolution was observed (Q₁₂₀ = 70%), compared with pure drug powder (Q₁₂₀ = 15%). In conclusion, dissolution of nimesulide can be modulated using an appropriate blend of pharmaceutical adjuvants.     

Assessment of B4C reaction with liquid iron alloys

The degree of reaction achieved when B₄C powders are brought into contact with liquid iron alloys has been assessed by a levitation dispersion test. Reaction occurs rapidly, leading to boron carbide dissolution and iron boride formation. In carbon-free iron alloys borocarbide, Fe₂₃(C, B)₆, also forms and in low-carbon iron alloys free graphite was also formed. Highcarbon alloys reacted to form both Fe₃(C, B) and free graphite. Attempts to provide protection for the B₄C by forming a TiC coating on its surface byin situ reactions with liquid Fe-Ti and Fe-Ti-C alloys proved unsuccessful, with TiC forming as a dispersed phase throughout the iron matrix     

Superplasticity of Fe3Al(Cr)

Abstract

The superplasticity of an Fe₃Al based intermetallic alloy with 3 at.-% chromium has been investigated in the strain rate range 10^-5-10^-2 s^-1 at test temperatures between 700 and 900°C. The composition of the iron aluminide was Fe–28Al–3Cr (at.-%) with additions of titanium and carbon. After thermomechanical processing the material possessed a coarse grained microstructure with an average grain size of 55 ± 10 μm. Strain rate exponents of 0·33≤m≤0.42 were recorded at strain rates of approximately 10^-5-10^-3 s^-1 in the temperature range 750-900°C. Superplastic elongations of 350% and more were achieved. From thermal activation analysis of superplastic flow, an activation energy of 185 ± 10 kJ mol^-1 was derived. This value is comparable to activation energies of superplastic flow in Fe₃Al(Ti) alloys. However, in unalloyed Fe₃Al the activation energy is higher, ~ 263 kJ mol^-1. Optical microscopy showed grain refinement to ~ 30 ± 5 μm in size in superplastically strained tensile specimens. Transmission electron microscopy gave evidence of the formation of subgrains of 0·3–0·5 μm in size. Superplasticity in this iron aluminide is mainly attributed to viscous dislocation glide, controlled by solute drag in the transformed B2 lattice at the deformation temperatures. During superplastic deformation, subgrain formation and grain refinement in the gauge length were revealed. From this it is concluded that dynamic recrystallisation makes an important contribution to the deformation mechanism of superplastic flow in this material.     

Reducing dissolution of MnO2 nanofibers by doping with ferric ion

MnO₂ nanofiber was found to possess high adsorption capacities for heavy metal ions such as, arsenic and lead, in water due to its high specific surface area (SSA) and high surface activity. However, a significant amount of manganese was found to leach from MnO₂ nanofibers. Reducing MnO₂ dissolution is very important for improving its applications in drinking water treatment. In this study, MnO₂ nanofiber was doped with Fe³⁺ to reduce its dissolution in water. Dissolution tests were conducted on un-doped and Fe-doped MnO₂ nanofibers. The results revealed that doping with Fe³⁺ significantly reduced MnO₂ dissolution. SSA and defects of MnO₂ materials were analyzed by BET and XRD methods. The effects of Fe³⁺ on MnO₂ dissolution were discussed and the optimal dopant amount was identified.