Numerical investigation of screw design influence on screw feeding in a roller compactor

Roller compaction refers to a dry granulation process where fine particulate feed is fed to the counter rotating rolls of a roller compactor to form ribbons which are further milled to produce free flowing agglomerates. For the continuous production of ribbons, there needs to be an adequate supply of powder by the screw to the rolls without any interruptions. In general, screws used in roller compactors are designed to convey powders of all types (cohesive, bulky, compressible, etc.), whereby usage of different screw designs for different powder types may be avoided. However, using such single screw type roller compactors for poor flowing powders may be challenging. On the other hand, the selection of the right screw for a given powder can only be done based on a combination of prior experience and trial-and-error experimentation. Empirical correlations exist to predict the draw down rate of screw feeders depending on their design, however, these correlations assume that there is continuous supply of powder by the screw, which limits its application to free-flowing powders only. To address this, in this study numerical simulations are performed based on discrete element method (DEM) to investigate the impact of screw design on the powder supply to rolls for cohesive and poorly flowing powders. The geometry considered includes a hopper, horizontal feeding screw below the hopper, and two counter-rotating rolls at the end of the screw. Two different screw designs are investigated where the main difference between them is the pitch length. The influence of scraper speed is investigated. Additionally, the influence of material attribute such as cohesion is studied. For both designs, the simulation results calculated include the rate of powder supply by the screw, velocity of particles in the screw etc. The simulation results of powder supply rate are also compared with results obtained based on empirical correlation. Overall, this simulation approach helps in selecting appropriate screw design for the given cohesive powder

Enhanced tenacity of mycobacterial aerosols from necrotic neutrophils

The tuberculosis agent Mycobacterium tuberculosis is primarily transmitted through air, but little is known about the tenacity of mycobacterium-containing aerosols derived from either suspensions or infected neutrophils. Analysis of mycobacterial aerosol particles generated from bacterial suspensions revealed an average aerodynamic diameter and mass density that may allow distant airborne transmission. The volume and mass of mycobacterial aerosol particles increased with elevated relative humidity. To more closely mimic aerosol formation that occurs in active TB patients, aerosols from mycobacterium-infected neutrophils were analysed. Mycobacterium-infected intact neutrophils showed a smaller particle size distribution and lower viability than free mycobacteria. In contrast, mycobacterium-infected necrotic neutrophils, predominant in M. tuberculosis infection, revealed particle sizes and viability rates similar to those found for free mycobacteria, but in addition, larger aggregates of viable mycobacteria were observed. Therefore, mycobacteria are shielded from environmental stresses in multibacillary aggregates generated from necrotic neutrophils, which allows improved tenacity but emphasizes short distance transmission between close contacts

Author Correction: Enhanced tenacity of mycobacterial aerosols from necrotic neutrophils

The original version of this Article contained errors within the affiliations section. Affiliation 4 was incorrectly given as ‘Leibniz Research Alliance INFECTIONS’21, Leipzig, Germany’. The correct affiliation is listed below: Leibniz Research Alliance INFECTIONS’21, Borstel, 23845, Germany Also, Affiliation 5 was incorrectly given as ‘German Center for Infection Research, TTU-TB, Borstel, 23845, Germany’. The correct affiliation is listed below: German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel, Germany. Finally, the original HTML version of this Article omitted an affiliation for G. Gabriel. The correct affiliations for G. Gabriel are listed below: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, 20251, Germany. Leibniz Research Alliance INFECTIONS’21, Borstel, 23845, Germany. German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel, Germany. These errors have now been corrected in the PDF and HTML versions of the Article

Characterisation of nasal devices for delivery of insulin to the brain and evaluation in humans using functional magnetic resonance imaging

This study aimed to characterise three nasal drug delivery devices to evaluate their propensity to deliver human insulin solutions to the nasal cavity for redistribution to the central nervous system. Brain delivery was evaluated using functional magnetic resonance imaging to measure regional cerebral blood flow. Intranasal insulin administration has been hypothesised to exploit nose-to-brain pathways and deliver drug directly to the brain tissue whilst limiting systemic exposure. Three nasal pump-actuator configurations were compared for delivery of 400 IU/mL insulin solution by measuring droplet size distribution, plume geometry, spray pattern and in vitro deposition in a nasal cast. The device with optimal spray properties for nose to brain delivery (spray angle between 30° and 45°; droplet size between 20 and 50 μm) also favoured high posterior-superior deposition in the nasal cast and was utilised in a pharmacological magnetic resonance imaging study. Functional magnetic resonance imaging in healthy male volunteers showed statistically significant decreases in regional cerebral blood flow within areas dense in insulin receptors (bilateral amygdala) in response to intranasally administered insulin (160 IU) compared to saline (control). These changes correspond to the expected effects of insulin in the brain and were achieved using a simple nasal spray device and solution formulation. We recommend that a thorough characterisation of nasal delivery devices and qualitative/quantitative assessment of the administered dose is reported in all studies of nose to brain delivery so that responses can be evaluated with respect to posology and comparison between studies is facilitated

Quantitative Analysis of Glassy State Relaxation and Ostwald Ripening during Annealing Using Freeze-Drying Microscopy

Supercooling during the freezing of pharmaceutical solutions often leads to suboptimal freeze-drying results, such as long primary drying times or a collapse in the cake structure. Thermal treatment of the frozen solution, known as annealing, can improve those issues by influencing properties such as the pore size and collapse temperature of the lyophilisate. In this study we aimed to show that annealing causes a rearrangement of water molecules between ice crystals, as well as between the freeze-concentrated amorphous matrix and the crystalline ice phase in a frozen binary aqueous solution. Ice crystal sizes, as well as volume fractions of the crystalline and amorphous phases of 10% (w/w) sucrose and trehalose solutions, were quantified after annealing using freeze-drying microscopy and image labelling. Depending on the annealing time and temperature, the amorphous phase was shown to decrease its volume due to the crystallisation of vitreous water (i.e., glassy state relaxation) while the crystalline phase was undergoing coarsening (i.e., Ostwald ripening). These results allow, for the first time, a quantitative comparison of the two phenomena. It was demonstrated that glassy state relaxation and Ostwald ripening, although occurring simultaneously, are distinct processes that follow different kinetics

Lipobiotin-capture magnetic bead assay for isolation, enrichment and detection of Mycobacterium tuberculosis from saliva.

BackgroundPulmonary Tuberculosis (TB) is diagnosed through sputum samples. As sputum sampling is challenging in children and cachexic patients, the development of diagnostic tests using saliva appears promising but has been discouraged due to low bacterial load and poor sensitivity. Here, we present a novel and rapid method to enrich Mycobacterium tuberculosis (Mtb) from saliva, which may serve as a basis for a diagnostic saliva test.MethodsLipobiotin-functionalized magnetic beads (LMBs) were incubated with Mtb-spiked PBS and saliva from healthy donors as well as with saliva from TB patients. Flow cytometry was used to evaluate the capacity of the beads to bind Mtb, while real-time quantitative polymerase chain reaction (qPCR) was utilized to detect Mtb and determine the amount of mycobacterial DNA in different sample types.ResultsWe found that LMBs bind Mtb efficiently when compared to non-functionalized beads. The development of an qPCR assay based on the use of LMBs (LMB assay) allowed us to enrich mycobacterial DNA in spiked sample types, including PBS and saliva from healthy donors (enrichment of up to ~8.7 fold). In Mtb-spiked saliva samples, we found that the LMB assay improved the detection rate of 102 bacteria in a volume of 5 ml from 0 out of 15 (0%) to 6 out of 15 (40%). Consistent with that, the LMB assay increased the rate of correctly identified saliva samples from TB patients in two independent cohorts.ConclusionsImplementation of the principle of the LMB-based assay may improve the sensitivity of existing diagnostic techniques, e.g. by functionalizing materials that facilitate Mtb sampling from the oral cavity