Influence of Metronidazole Particle Properties on Granules Prepared in a High-Shear Mixer-Granulator

ABSTRACT

Metronidazole is a good example of high-dose drug substance with poor granulating and tableting properties. Tablets are generally produced by liquid granulation; however, the technological process failure is quite frequent. In order to verify how the metronidazole particle characteristics can influence granule properties, three metronidazole batches differing for crystal habit, mean particle size, BET surface area and wettability were selected, primarily designed according to their different elongation ratio: needle-shaped, stick-shaped, and isodimensional. In the presence of lactose monohydrate and pregelatinized maize starch, respectively as diluent and binder, they were included in a formula for wet granulation in a high-shear mixer-granulator. In order to render the process comparable as far as possible, all parameters and experimental conditions were maintained constant. Four granule batches were obtained: granules from placebo (G-placebo), granules from needle-shaped crystals (G-needle-shaped), granules from stick-shaped crystals (G-stick-shaped), and granules from isodimensional crystals (G-isodimensional). Different granule properties were considered, in particular concerning porosity, friability, loss on drying (LOD), and flowability. In order to study their tabletability and compressibility, the different granules obtained were then compressed in a rotary press. The best tabletability was obtained with the isodimensional batch, while the poorest was exhibited by the stick-shaped one. Differences in tabletability are in good accordance with compressibility results: to a better tabletability corresponds an important granule ability to undergo a volume reduction as a result of an applied pressure. In particular, it was proposed that the greatest compressibility of the G-isodimensional must be related to the greatest granule porosity percentage.     

Bootstrap Unit‐Root Tests: Comparison and Extensions

Abstract. In this article, we study and compare the properties of several bootstrap unit‐root tests recently proposed in the literature. The tests are Dickey–Fuller (DF) or Augmented DF, based either on residuals from an autoregression and the use of the block bootstrap or on first‐differenced data and the use of the stationary bootstrap or sieve bootstrap. We extend the analysis by interchanging the data transformations (differences vs. residuals), the types of bootstrap and the presence or absence of a correction for autocorrelation in the tests. We show that two sieve bootstrap tests based on residuals remain asymptotically valid. In contrast to the literature which focuses on a comparison of the bootstrap tests with an asymptotic test, we compare the bootstrap tests among themselves using response surfaces for their size and power in a simulation study. This study leads to the following conclusions: (i) augmented DF tests are always preferred to standard DF tests; (ii) the sieve bootstrap performs better than the block bootstrap; (iii) difference‐based tests appear to have slightly better size properties, but residual‐based tests appear more powerful.     

Micropillar Testing of Amorphous Silica

Amorphous silica exhibits a complex mechanical response. The elastic regime is highly nonlinear while plastic flow does not conserve volume, resulting in densification. As a result the quantification of a reliable constitutive equation is a difficult task. We have assessed the potential of micropillar compression testing for the investigation of the micromechanical properties of amorphous silica. We have calculated the response of amorphous silica micropillars as predicted by finite element analysis. The results were compared to preliminary microcompression tests. In the calculations, an advanced constitutive law including plastic response, densification, and strain hardening was used. Special attention was paid to the evaluation of the impact of substrate compliance, pillar misalignment, and friction conditions. We find that amorphous silica is much more amenable than some metals to microcompression experiments due to a comparatively high ratio between yield stress and elastic modulus. The simulations are found to be very consistent with the experimental results. However, full agreement cannot be obtained without allowance for the nonlinear response of amorphous silica in the elastic regime.     

Effect of shear stress and growth conditions on detachment and physical properties of biofilms

Detachment is one of the major processes determining the physical structure and microbial functionalities of biofilms. To predict detachment, it is necessary to take the mechanical properties of the biofilm and the effect of both hydrodynamic and growth conditions into account. In this work, experiments were conducted with biofilms developed under various shear stresses and with various substrate natures. In addition, two cases were considered in order to differentiate between the effect of hydrodynamic factors and growth factors: the biofilms were directly grown under the targeted shear stress (τ) condition or they were precultivated under very low shear stress (0.01 Pa) and then exposed to high shear stress in the range of 0.1-13 Pa. An exponential and asymptotic decrease of the biofilm thickness and mass with increasing τ was observed in both cases. On contrary density, expressed as the biofilm dry mass on a known substratum divided by the average thickness increased with τ. Denitrifying biofilms always showed greater thickness and density than oxic biofilms. These results showed the presence of a compact basal layer that resisted shear stresses as high as 13 Pa whatever the culture conditions. Above this basal layer, the cohesion was lower and depended on the shear stress applied during biofilm development. The application of shear stress to the biofilms resulted in both detachment and compression, but detachment prevailed for the upper part of the biofilms and compression prevailed for the basal layers. A model of biofilm structure underlying the stratified character of this aggregate is given in terms of density and cohesion.     

Characteristic time of strain induced crystallization of crosslinked natural rubber

Real time Wide-Angle X-ray Scattering (WAXS) measurements during cyclic tensile tests at high strain rates (from 8 s^?1–280 s^?1) and at room temperature on crosslinked Natural Rubber (NR) are performed thanks to a specific homemade device. From the observed influence of the frequency on the crystallization index at the maximum sample elongation, a characteristic crystallization time is deduced. This is done taking into account the material self-heating during such unusually high strain rates. Two regimes for the dynamic process of strain induced crystallization are evidenced. For the NR tested, the obtained characteristic time is around 20 ms when the material average elongation during the cyclic test is above a critical elongation value λ_c. λ_c is the minimum elongation needed to induce crystallization during low strain rate tensile tests. Moreover, a rapid increase of this characteristic time is found when the average elongation decreases below this critical value.     

Effects of Pulsed Electric Fields on Cabernet Sauvignon Grape Berries and on the Characteristics of Wines

The treatment of Cabernet Sauvignon red grapes by pulsed electric fields (PEFs) is performed prior to vinification in order to enhance the extraction of polyphenols. PEF treatments of the longest duration and of the highest energy (E?= 0.7 kV/cm, t _PEF?=?200 ms, W?=?31 Wh/kg) changed the structure of grape skins and produced a wine that was richer in tannins (34 %), while treatment of the highest strength (E?=?4 kV/cm, t _PEF?=?1 ms, W =?4 Wh/kg) altered the visual appearance of phenolic compounds in the skins and led to greater extraction of the anthocyanins (19 %). The PEF treatments caused the depolymerization of skin tannins, improving the diffusion of these decondensed tannins which are smaller. The PEF treatment of longest duration and of the highest energy had more impact on the parietal tannins and the cell walls of the skins while treatment of the highest strength modified more the vacuolar tannins. Changes in the operating parameters of the PEF treatment (E?=?0.7 to 4 kV/cm, t _PEF?=?1 to 200 ms, W?=?4 to 31 Wh/kg) did not affect alcohol content, total acidity nor volatile acidity in finished wines compared to the values of the control wine, but seemed to cause a slight increase in pH (1–2 %).     

Fungal pretreatment of wheat straw: Effects on the biodegradability of cell walls,structural polysaccharides,lignin and phenolic acids by rumen microorganisms

Disappearance of cell wall components of untreated straw and straw treated with the ligninolytic white-rot fungi Phanerochaete chrysosporium, Dichomitus squalens and Cyathus stercoreus were determined during the course of rumen digestion of samples in nylon bags. The first fungus degraded hemicelluloses and cellulose non-selectively, adversely affecting the digestion rate of crude cell walls. Dichomitus squalens and C. stercoreus preferentially degraded hemicelluloses and lignin, affording cell wall degradation rates 1.5 times higher than in native straw. Furthermore, the extent of cell wall digestion was also significantly enhanced. Both strains improved the extent of cellulose digestion, whereas the potentially degradable xylan fraction remained unchanged. Polysaccharide digestion rates were influenced in different ways depending on the strain tested: straw degraded by C. stercoreus showed an increase in cellulose digestion rate by 50%, whereas residual arabinose units were slowly degraded. Xylan was degraded 1.8 times faster in straw decayed' by D. squalens, while cellulose digestion remained unchanged. Phanerochaete chrysosporium depressed both xylan and cellulose digestion rates. Fungal-treated lignins were solubilised in the rumen faster than in untreated straw, whereas only treatment by C. stercoreus resulted in higher lignin losses. Esterified phenolic acids were extensively degraded by all three fungi. Residual ferulic and p-coumaric acids accumulated during rumen digestion, although only the former decreased in the original straw.     

Crystallization of fluorescent quantum dots within a three-dimensional bio-organic template of actin filaments and lipid membranes

Biological molecules and molecular self-assemblies are promising templates to organize well-defined inorganic nanostructures. We demonstrate the ability of a self-assembled three-dimensional crystal template of helical actin protein filaments and lipids bilayers to generate a hierarchical self-assembly of quantum dots. Functionnalized tricystein peptidic quantum dots (QDs) are incorporated during the dynamical self-assembly of this actin/lipid template resulting in the formation of crystalline fibers. The crystal parameters, 26.5×18.9×35.5 nm3, are imposed by the membrane thickness, the diameter, and the pitch of the actin self-assembly. This process ensures the high quality of the crystal and results in unexpected fluorescence properties. This method of preparation offers opportunities to generate crystals with new symmetries and a large range of distance parameters.     

Control of visual conditions for open-plan offices

This paper reports insights about energy savings in buildings dedicated to tertiary activity. The goal is to employ as much as possible natural light flows to minimize the artificial light source consumption. Although the solar energy is power-efficient to light and heat a room, this natural source remains complex to manage and can generate inconveniences related to occupants visual comfort. The authors propose a global solution to deal with visual comfort by controlling the daylight contribution to the indoor light atmosphere. This control structure is based on the use of an innovative sensor of light conditions and it was implemented within an experimental room equipped with classic Venetian blinds. This paper focuses on the control laws to apply in order to meet visual needs for current tasks performed in offices.     

SBA-15 mesoporous silica modified with rhodium by MDD method and its catalytic role for N<Subscript>2</Subscript>O decomposition reaction

SBA-15 mesoporous silicas modified with rhodium were studied as catalysts for the N₂O decomposition reaction. Rhodium was deposited on SBA-15 by the Molecular Designed Dispersion (MDD) method using Rh(acac)₃ as a precursor of active phase. The same method was used for the deposition of Cu, Fe, Al and Ti. The SBA-15 support modified with metals were characterized with respect to metal loading (EPMA), structure (XRD), texture (BET), morphology (SEM), Rh dispersion (oxygen chemisorption), surface acidity (pyridine adsorption) and chemical nature of introduced copper and iron species (UV–vis-DRS). The rhodium-containing SBA-15 samples were found to be active catalysts for the N₂O decomposition reaction. Deposition of Al on the Rh-loaded catalyst increased its activity. An opposite effect was observed for the samples modified with Cu and Fe.