Effect of water vapour stabilization of raw materials on the quality of the inhalation product

Generation of raw materials for dry powder inhalers by different size reduction methods can be expected to influence physical and chemical properties of the powders. This can cause differences in particle size, size distribution, shape, crystalline properties, surface texture and energy. These physical properties of powders influence the behaviour of particles before and after inhalation. Materials with an amorphous surface have different surface energy compared to materials with crystalline surface. This can affect the adhesion and cohesion of particles. Changes in the surface nature of the drug particles results in a change in product performance. By stabilization of the raw materials the amorphous surfaces are converted into crystalline surfaces. The primary aim of the study was to investigate the influence of the surface properties of the inhalation particles on the quality of the product. The quality of the inhalation product is evaluated by measuring the fine particle dose (FPD). FDP is the total dose of particles with aerodynamic diameters smaller than 5,0 μm. The secondary aim of this study was to achieve the target level of the FPD and the stability of the FPD. This study was also used to evaluate the importance of the stabilization of the inhalation powders. The study included manufacturing and analysing drug substance 200 μg/dose inhalation powder batches using non-stabilized or stabilized raw materials. The inhaler formulation consisted of micronized drug substance, lactose <100μm and micronized lactose <10μm. The inhaler device was Easyhaler®. Stabilization of the raw materials was done in different relative humidity, temperature and time. Surface properties of the raw materials were studied by dynamic vapour sorption, scanning electron microscopy and three-point nitrogen adsorption technique. Particle size was studied by laser diffraction particle size analyzer. Aerodynamic particle size distribution from inhalers was measured by new generation impactor. Stabilization of all three raw materials was successful. A clear difference between nonstabilized and stabilized raw materials was achieved for drug substance and lactose <10μm. However for lactose <100μm the difference wasn’t as clear as wanted. The surface of the non-stabilized drug substance was more irregular and the particles had more roughness on the surface compared to the stabilized drug substances particles surface. The surface of the stabilized drug particles was more regular and smoother than non-stabilized. Even though a good difference between stabilized and non-stabilized raw materials was achieved, a clear evidence of the effect of the surface properties of the inhalation particles on the quality of the product was not observed. Stabilization of the raw materials didn’t lead to a higher FPD. Possible explanations for the unexpected result might be too rough conditions in the stabilization of the drug substance or smaller than wanted difference in the degree of stabilization of the main component of the product <100μm. Despite positive effects on the quality of the product were not seen there appears to be some evidence that stabilized drug substance results in smaller particle size of dry powder inhalers.

Effect of strain rate on the high-temperature low-cycle fatigue properties of a nimonic PE-16 superalloy

Strain-rate effects on the low-cycle fatigue (LCF) behavior of a NIMONIC PE-16 superalloy have been evaluated in the temperature range of 523 to 923 K. Total-strain-controlled fatigue tests were per-formed at a strain amplitude of +/-0.6 pct on samples possessing two different prior microstructures: microstructure A, in the solution-annealed condition (free of gamma' and carbides); and microstructure B, in a double-aged condition with gamma' of 18-nm diameter and M23C6 carbides. The cyclic stress response behavior of the alloy was found to depend on the prior microstructure, testing temperature, and strain rate. A softening regime was found to be associated with shearing of ordered gamma' that were either formed during testing or present in the prior microstructure. Various manifestations of dynamic strain aging (DSA) included negative strain rate-stress response, serrations on the stress-strain hysteresis loops, and increased work-hardening rate. The calculated activation energy matched well with that for self-diffusion of Al and Ti in the matrix. Fatigue life increased with an increase in strain rate from 3 x 10(-5) to 3 x 10(-3) s-1, but decreased with further increases in strain rate. At 723 and 823 K and low strain rates, DSA influenced the deformation and fracture behavior of the alloy. Dynamic strain aging increased the strain localization in planar slip bands, and impingement of these bands caused internal grain-boundary cracks and reduced fatigue life. However, at 923 K and low strain rates, fatigue crack initiation and propagation were accelerated by high-temperature oxidation, and the reduced fatigue life was attributed to oxidation-fatigue interaction. Fatigue life was maximum at the intermediate strain rates, where strain localization was lower. Strain localization as a function of strain rate and temperature was quantified by optical and scanning electron microscopy and correlated with fatigue life.

Time Evolution of the Microstructure of VO2(B) Films Deposited on Glass by MOCVD

Thin films of VO2(B), a metastable polymorph of vanadium dioxide, have been grown on glass by low-pressure metalorganic chemical vapor deposition (MOCVD). The films grown for 90 minutes have atypical microstructure, comprising micrometer-sized, island-like entities made up of numerous small, single-crystalline platelets (≅1 μm) emerging orthogonally from larger ones at the center. Microstructure evolution as a function of deposition time has been examined by X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The metastable VO2(B) transforms to the stable rutile (R) phase at 550°C in inert ambient, which on cooling convert reversibly to M phase. Electron microscopy shows that annealing leads to the disintegration of the VO2(B) platelets into small crystallites of the rutile phase VO2(R), although the platelet morphology is retained. The magnitude of the jump in resistance at the semiconductor-to-metal, VO2(M)→VO2(R) phase transition depends on the arrangement of polycrystalline platelets in the films.

Time dependent deformations in concrete: A multi-scale approach

Estimation of creep and shrinkage are critical in order to compute loss of prestress with time in order to compute leak tightness and assess safety margins available in containment structures of nuclear power plants. Short-term creep and shrinkage experiments have been conducted using in-house test facilities developed specifically for the present research program on 35 and 45 MPa normal concrete and 25 MPa heavy density concrete. The extensive experimental program for creep, has cylinders subject to sustained levels of load typically for several days duration (till negligible strain increase with time is observed in the creep specimen), to provide the total creep strain versus time curves for the two normal density concrete grades and one heavy density concrete grade at different load levels, different ages at loading, and at different relative humidity’s. Shrinkage studies on prism specimen for concrete of the same mix grades are also being studied. In the first instance, creep and shrinkage prediction models reported in the literature has been used to predict the creep and shrinkage levels in subsequent experimental data with acceptable accuracy. While macro-scale short experiments and analytical model development to estimate time dependent deformation under sustained loads over long term, accounting for the composite rheology through the influence of parameters such as the characteristic strength, age of concrete at loading, relative humidity, temperature, mix proportion (cement: fine aggregate: coarse aggregate: water) and volume to surface ratio and the associated uncertainties in these variables form one part of the study, it is widely believed that strength, early age rheology, creep and shrinkage are affected by the material properties at the nano-scale that are not well established. In order to understand and improve cement and concrete properties, investigation of the nanostructure of the composite and how it relates to the local mechanical properties is being undertaken. While results of creep and shrinkage obtained at macro-scale and their predictions through rheological modeling are satisfactory, the nano and micro indenting experimental and analytical studies are presently underway. Computational mechanics based models for creep and shrinkage in concrete must necessarily account for numerous parameters that impact their short and long term response. A Kelvin type model with several elements representing the influence of various factors that impact the behaviour is under development. The immediate short term deformation (elastic response), effects of relative humidity and temperature, volume to surface ratio, water cement ratio and aggregate cement ratio, load levels and age of concrete at loading are parameters accounted for in this model. Inputs to this model, such as the pore structure and mechanical properties at micro/nano scale have been taken from scanning electron microscopy and micro/nano-indenting of the sample specimen.

The effect of electrochemical lithiation on physicochemical properties of RF-sputtered Sn thin films

Thin films of Sn were deposited on Pt/Si substrates by sputtering technique and subjected to electrochemical lithiation studies. Electrochemical lithiation of Sn resulted in the formation of Sn-Li alloys of different compositions. Charging of Sn-coated Pt/Si electrodes was terminated at different potentials and the electrodes were examined for physicochemical properties. The scanning electron microscopy and atomic force microscopy images suggested that the Sn films expanded on lithiation. Roughness of the film increased with an increase in the quantity of Li present in Sn-Li alloy. Electrochemical impedance data suggested that the kinetics of charging became sluggish with an increase in the quantity of Li in Sn-Li alloy.

Dielectric properties of DC reactive magnetron sputtered Al2O3 thin films

Alumina (Al2O3) thin films were sputter deposited over well-cleaned glass and Si < 100 > substrates by DC reactive magnetron sputtering under various oxygen gas pressures and sputtering powers. The composition of the films was analyzed by X-ray photoelectron spectroscopy and an optimal O/Al atomic ratio of 1.59 was obtained at a reactive gas pressure of 0.03 Pa and sputtering power of 70 W. X-ray diffraction results revealed that the films were amorphous until 550 degrees C. The surface morphology of the films was studied using scanning electron microscopy and the as-deposited films were found to be smooth. The topography of the as-deposited and annealed films was analyzed by atomic force microscopy and a progressive increase in the rms roughness of the films from 3.2 nm to 4.53 nm was also observed with increase in the annealing temperature. Al-Al2O3-Al thin film capacitors were then fabricated on glass substrates to study the effect of temperature and frequency on the dielectric property of the films. Temperature coefficient of capacitance. AC conductivity and activation energy were determined and the results are discussed. (C) 2011 Elsevier B.V. All rights reserved.

Two new species of Nitzschia (Bacillariophyta) from shallow wetlands of Peninsular India

The majority of species belonging to the genus Nitzschia are distinguished by minute taxonomic features that are difficult to observe and document. Currently, geographical distributions for many species are recognized as cosmopolitan; in contrast endemic species are poorly documented and studied. Our study describes two new species of Nitzschia from shallow wetlands across the Bangalore urban district of peninsular India, Nitzschia taylorii, sp. nov. and Nitzschia williamsi, sp. nov. Morphological analyses of these new species were performed with light and scanning electron microscopy, and the ecology of inhabited wetlands are discussed briefly. New species records from urban polluted wetlands provide evidence for broadening taxonomic and ecological investigations of cosmopolitan genera like Nitzschia in the Southern Hemisphere.

Simple coating technique for 2-dimensional zinc oxide nanostructure

We report a novel and simple solution-based technique for depositing 2-D zinc oxide platelets at low temperature. Nanoplatelets that were mostly a-oriented associated with the Lotgering orientation factor of 0.65 were obtained by locating a glass substrate at a distance of about 5cm over the aqueous vapour of the boiling precursor. Experiments were carried out to optimize the coating parameters by placing the substrate at different positions, durations and the pH of the precursor. The X-ray diffraction studies confirmed the structure associated with the crystallites to be wurzite. The different morphology of the zinc oxide films and blue light emission were observed using scanning electron microscopy and fluorescence spectroscopy respectively.

Morphology dependent electrochemical performance of sputter deposited Sn thin films

This study deals with tailoring of the surface morphology, microstructure, and electrochemical properties of Sn thin films deposited by magnetron sputtering with different deposition rates. Scanning electron microscopy and atomic force microscopy are used to characterize the film surface morphology. Electrochemical properties of Sn thin film are measured and compared by cyclic voltammetry and charge-discharge cycle data at a constant current density. Sn thin film fabricated with a higher deposition rate exhibited an initial discharge capacity of 798 mAh g(-1) but reduced to 94 mAh g(-1) at 30th cycle. Film deposited with lower deposition rate delivered 770 mAh g(-1) during 1st cycle with improved capacity retention of 521 mAh g(-1) on 30th cycle. Comparison of electrochemical performances of these films has revealed important distinctions, which are associated with the surface morphology and hence on rate of deposition. (C) 2012 Elsevier Ltd. All rights reserved.

Detailed investigation of a gamma-cyclodextrin inclusion complex with L-thyroxine for improved pharmaceutical formulations

Thyroxine is a naturally occurring human hormone produced by the thyroid gland. Clinical applications of thyroxine to treat several chronic disorders are limited by poor water solubility and instability under physiological conditions. An inclusion complex of levo-thyroxine (l-thyroxine), the active form of the hormone with gamma cyclodextrin (gamma-CD) has been obtained and studied with the aim of improving oral delivery rather than the injection formulation of the sodium salt. In addition to greater patient acceptability, inclusion complexes often improve aqueous solubility and bioavailability, stability, and reduce toxicity of drugs, thus providing enhanced pharmaceutical formulations. Physicochemical characterization of the inclusion complex was carried out using Fourier transform infrared spectroscopy, X-ray diffractometry, differential scanning calorimetry, scanning electron microscopy and proton nuclear magnetic resonance spectroscopy. Intermolecular dipolar interactions for the inclusion complex were also studied using 2 dimensional ROESY experiments. Formation of the inclusion complex between the protons H3 and H5 of cyclodextrin with aromatic protons of thyroxine was confirmed by their dipolar interaction. Molecular modelling was used to understand the basis for the complex formation and predict the formation of other complexes. Interestingly, we found that l-thyroxine forms an inclusion complex only with the larger gamma-CD and not with other available alpha and beta forms.

Modeling of agglomeration inside a droplet with nanosuspensions in an acoustic field

This short communication reports results of particle agglomeration details of an acoustically levitated nanosilica droplet. The droplet undergoes thermo-physical and morphological changes under external heating load (convective or radiative) forming different solid structures due to particle agglomeration. We report an agglomeration model based on population balance approach coupled with species and energy conservation equations in the liquid phase and compare it with the experimentally observed structure formations using high speed photography. The analysis is able to predict similar spherical bowl shaped morphologies as observed experimentally using scanning electron microscopy and laser induced fluorescence. (C) 2012 Elsevier Ltd. All rights reserved.

Thermoelectric properties of Zn doped Cu2SnSe3

Zn doped ternary compounds Cu2ZnxSn1-xSe3 (x = 0, 0.025, 0.05, 0.075) were prepared by solid state synthesis. The undoped compound showed a monoclinic crystal structure as a major phase, while the doped compounds showed a cubic crystal structure confirmed by powder XRD (X-Ray Diffraction). The surface morphology and elemental composition analysis for all the samples were studied by SEM (Scanning Electron Microscopy) and EPMA (Electron Probe Micro Analyzer), respectively. SEM micrographs of the hot pressed samples showed the presence of continuous and homogeneous grains confirming sufficient densification. Elemental composition of all the samples revealed an off-stoichiometry, which was determined by EPMA. Transport properties were measured between 324 K and 773 K. The electrical resistivity decreased up to the samples with Zn content x = 0.05 in Cu2ZnxSn1-xSe3, and slightly increased in the sample Cu2Zn0.075Sn0.925Se3. This behavior is consistent with the changes in the carrier concentration confirmed by room temperature Hall coefficient data. Temperature dependent electrical resistivity of all samples showed heavily doped semiconductor behavior. All the samples exhibit positive Seebeck coefficient (S) and Hall coefficient indicating that the majority of the carriers are holes. A linear increase in Seebeck coefficient with increase in temperature indicates the degenerate semiconductor behavior. The total thermal conductivity of the doped samples increased with a higher amount of doping, due to the increase in the carrier contribution. The total and lattice thermal conductivity of all samples showed 1/1 dependence, which points toward the dominance of phonon scattering at high temperatures. The maximum 1/TZF = 0.48 at 773 K was obtained for the sample Cu2SnSe3 due to a low thermal conductivity compared to the doped samples. (C) 2014 Elsevier B.V. All rights reserved.

Double Gaussian distribution of barrier height observed in densely packed GaN nanorods over Si (111) heterostructures

GaN nanorods were grown by plasma assisted molecular beam epitaxy on intrinsic Si (111) substrates which were characterized by powder X-ray diffraction, field emission scanning electron microscopy, and photoluminescence. The current-voltage characteristics of the GaN nanorods on Si (111) heterojunction were obtained from 138 to 493K which showed the inverted rectification behavior. The I-V characteristics were analyzed in terms of thermionic emission model. The temperature variation of the apparent barrier height and ideality factor along with the non-linearity of the activation energy plot indicated the presence of lateral inhomogeneities in the barrier height. The observed two temperature regimes in Richardson's plot could be well explained by assuming two separate Gaussian distribution of the barrier heights. (C) 2014 AIP Publishing LLC.

Porous membranes designed from bi-phasic polymeric blends containing silver decorated reduced graphene oxide synthesized via a facile one-pot approach

In this work, porous membranes were designed by selectively etching the PEO phase, by water, from a melt-mixed PE/PEO blend. The pure water flux and the resistance across the membrane were systematically evaluated by employing an indigenously developed cross flow membrane setup. Both the phase morphology and the cross sectional morphology of the membranes was assessed by scanning electron microscopy and an attempt was made to correlate the observed morphology with the membrane performance. In order to design antibacterial membranes for water purification, partially reduced graphene oxide (rGO), silver nanoparticles (Ag) and silver nanoparticles decorated with rGO (rGO-Ag) were synthesized and incorporated directly into the blends during melt mixing. The loss of viability of bacterial cells was determined by the colony counting method using E. coli as a model bacterium. SEM images display that the direct contact with the rGO-Ag nanoparticles disrupts the cell membrane. In addition, the rGO-Ag nanoparticles exhibited a synergistic effect with respect to bacterial cell viability in comparison to both rGO and Ag nanoparticles. The possible mechanism associated with the antibacterial activity in the membranes was discussed. This study opens new avenues in designing antibacterial membranes for water purification.

In Situ Observations On The Fracture Process Of Metallic Glassy Ribbons

Crack propagation and strain field evolution in two metallic glassy ribbons are studied using in situ scanning electron microscopy and the white digital speckle correlation method. Strain state at the crack tip, which depends heavily on the fracture toughness, plays a key role in fracture. A high degree of shear strain concentration in tough glassy ribbon can satisfy the critical shear strain, resulting in shear fracture, whereas a high degree of linear strain concentration in brittle glassy ribbon can initiate normal tensile fracture. (C) 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.