The role of several l-HPCs in preventing tablet capping during direct compression of metronidazole

Several low-hydroxypropyl cellulose (l-HPC) derivatives (LH-11, 21, 22, 31, and 32) differing in granulometric particle size or in hydroxypropyl content were considered in the present study. The l-HPC grades were characterized as pure powders, in order to determine both compression and densification behavior, in presence or in absence of magnesium stearate as lubricant, and then, were physically mixed in different proportions with metronidazole, which was also previously characterized as pure powder. The tabletability and compressibility of these binary mixtures were then evaluated, in presence or in absence magnesium stearate as lubricant at two different compression speeds (20 and 70 mm/sec). It was observed that both binary mixture compression behavior and capping tendency were influenced by compression speed and by the presence of lubricant. Differences in anti-capping efficiency between the l-HPCs may be related to their hydroxypropyl content. This parameter influences the interaction between the metronidazole and the polymer particles, and consequently the ability of the binary system to undergo densification under compression.     

Influence of metronidazole particle properties on granules prepared in a high-shear mixer-granulator

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.     

The Role of Several l-HPCs in Preventing Tablet Capping During Direct Compression of Metronidazole

Several low-hydroxypropyl cellulose (l-HPC) derivatives (LH-11, 21, 22, 31, and 32) differing in granulometric particle size or in hydroxypropyl content were considered in the present study. The l-HPC grades were characterized as pure powders, in order to determine both compression and densification behavior, in presence or in absence of magnesium stearate as lubricant, and then, were physically mixed in different proportions with metronidazole, which was also previously characterized as pure powder. The tabletability and compressibility of these binary mixtures were then evaluated, in presence or in absence magnesium stearate as lubricant at two different compression speeds (20 and 70 mm/sec). It was observed that both binary mixture compression behavior and capping tendency were influenced by compression speed and by the presence of lubricant.

Differences in anti-capping efficiency between the l-HPCs may be related to their hydroxypropyl content. This parameter influences the interaction between the metronidazole and the polymer particles, and consequently the ability of the binary system to undergo densification under compression.     

Condensation inside and outside smooth and enhanced tubes — a review of recent research

Condensation heat transfer, both inside and outside horizontal tubes, plays a key role in refrigeration, air conditioning and heat pump applications. In the recent years the science of condensation heat transfer has been severely challenged by the adoption of substitute working fluids and new enhanced surfaces for heat exchangers. Well-known and widely established semiempirical correlations to predict heat transfer during condensation may show to be quite inaccurate in some new applications, and consequently a renewed effort is now being dedicated to the characterisation of flow conditions and associated predictive procedures for heat transfer and pressure drop of condensing vapours, even in the form of zeotropic mixtures. This paper critically reviews the most recent results appeared in the open literature and pertinent to thermal design of condensers for the air conditioning and refrigeration industry; both in-tube and bundle condensation are considered, related to the use of plain and enhanced surfaces.     

Source and nature of inhaled atmospheric dust from trace element analyses of human bronchial fluids

Rapid volcanic eruptions quickly ejecting large amounts of dust provoke the accumulation of heavy metals in people living in surrounding areas. Analyses of bronchoalveolar lavage samples (BAL) collected from people exposed to the paroxysmal 2001 Etna eruption revealed a strong enrichment of many toxic heavy metals. Comparing the BAL to the dust composition of southeastern Sicily, we found that only V, Cr, Mn, Fe, Co, and U enrichment could be related to the volcanic event, whereas Ni, Cu, Cd, and Pb contents come from the dissolution of particles of anthropogenic origin. Furthermore, the nature of these inhaled anthropogenic particles was revealed by anomalous La and partially Ce concentrations in BAL that were consistent with a mixture of road dust and petroleum refinery emissions. Our results indicate that trace element distribution in BAL is a suitable tracer of human exposure to different sources of inhaled atmospheric particulates, allowing investigations into the origin of source materials inhaled by people subjected to atmospheric fallout.     

Yttrium and lanthanides in human lung fluids, probing the exposure to atmospheric fallout

Inhalation of airborne particles can produce crystallization of phosphatic microcrysts in intraaveolar areas of lungs, sometimes degenerating into pulmonary fibrosis. Results of this study indicate that these pathologies are induced by interactions between lung fluids and inhaled atmospheric dust in people exposed to volcanic dust ejected from Mount Etna in 2001. Here, the lung solid-liquid interaction is evaluated by the distribution of yttrium and lanthanides (YLn) in fluid bronchoalveolar lavages on selected individuals according the classical geochemical approaches. We found that shale-normalised patterns of yttrium and lanthanides have a 'V shaped' feature corresponding to the depletion of elements from Nd to Tb when compared to the variable enrichments of heavy lanthanides, Y, La and Ce. These features and concurrent thermodynamic simulations suggest that phosphate precipitation can occur in lungs due to interactions between volcanic particles and fluids. We propose that patterns of yttrium and lanthanides can represent a viable explanation of some pathology observed in patients after prolonged exposure to atmospheric fallout and are suitable to become a diagnostic parameter of chemical environmental stresses.     

A multiscale graph theoretical approach to gene regulation networks: a case study in atrial fibrillation

The changes in between gene expression correlation structure induced in heart tissue by atrial fibrillation are studied by means of a graph theoretical approach. As expected by general statistical mechanics principles, the disease increases the general connectivity of the gene regulation network; the multiscale character of the analysis allows us to get both a general appreciation of regulation network connectivity and the sketching of a biological interpretation of the studied disease. The presence of a still largely unknown, scale invariant, global correlation field encompassing the entire genome is demonstrated as well.     

Descriptors of wavefront propagation

This article presents two signal processing techniques for the analysis of intracardial electrograins in patients with atrial fibrillation (AF). The first, number of occurrences (NO), is aimed at quantifying the level of organization of the signal. The second, index of synchronization (IS), quantifies the degree of synchrony of electrograms from adjacent atrial sites. The proposed indexes are applied to multielectrode basket catheter recordings in patients with chronic or electrically induced AF     

P-wave morphology assessment by a gaussian functions-based model in atrial fibrillation patients

Aim of this study was to present a P-wave model, based on a linear combination of Gaussian functions, to quantify morphological aspects of P-wave in patients prone to atrial fibrillation (AF). Five-minute ECG recordings were performed in 25 patients with permanent dual chamber pacemakers. Patients were divided into high-risk and low-risk groups, including patients with and without AF episodes in the last 6 mo preceding the study, respectively. ECG signals were acquired using a 32-lead mapping system for high-resolution biopotential measurement (ActiveTwo, Biosemi, The Netherlands, sample frequency 2 kHz, 24-bit resolution). Up to 8 Gaussian models have been computed for each averaged P-wave extracted from every lead. The P-wave morphology was evaluated by extracting seven parameters. Classical time-domain parameters, based on P-wave duration estimation, have been also estimated. We found that the P-wave morphology can be effectively modeled by a linear combination of Gaussian functions. In addition, the combination of time-domain and morphological parameters extracted from the Gaussian function-based model of the P-wave improves the identification of patients having different risks of developing AF.