Modelling the Effect of Process Parameters on the Wet Extrusion and Spheronisation of High-Loaded Nicotinamide Pellets Using a Quality by Design Approach

Open access articleThe aim of the present study was to develop an alternative process to spray granulation in order to prepare high loaded spherical nicotinamide (NAM) pellets by wet extrusion and spheronisation. Therefore, a quality by design approach was implemented to model the effect of the process parameters of the extrusion-spheronisation process on the roundness, roughness and useable yield of the obtained pellets. The obtained results were compared to spray granulated NAM particles regarding their characteristics and their release profile in vitro after the application of an ileocolon targeted shellac coating. The wet extrusion-spheronisation process was able to form highly loaded NAM pellets (80%) with a spherical shape and a high useable yield of about 90%. However, the water content range was rather narrow between 24.7% and 21.3%. The design of experiments (DoE), showed that the spheronisation conditions speed, time and load had a greater impact on the quality attributes of the pellets than the extrusion conditions screw design, screw speed and solid feed rate (hopper speed). The best results were obtained using a low load (15 g) combined with a high rotation speed (900 m/min) and a low time (3–3.5 min). In comparison to spray granulated NAM pellets, the extruded NAM pellets resulted in a higher roughness and a higher useable yield (63% vs. 92%). Finally, the coating and dissolution test showed that the extruded and spheronised pellets are also suitable for a protective coating with an ileocolonic release profile. Due to its lower specific surface area, the required shellac concentration could be reduced while maintaining the release profil

Development and Validation of an In‐Line API Quantification Method Using AQbD Principles Based on UV‐Vis Spectroscopy to Monitor and Optimise Continuous Hot Melt Extrusion Process

open access journalA key principle of developing a new medicine is that quality should be built in, with a thorough understanding of the product and the manufacturing process supported by appropriate process controls. Quality by design principles that have been established for the development of drug products/substances can equally be applied to the development of analytical procedures. This paper presents the development and validation of a quantitative method to predict the concentration of piroxicam in Kollidon® VA 64 during hot melt extrusion using analytical quality by design principles. An analytical target profile was established for the piroxicam content and a novel in‐line analytical procedure was developed using predictive models based on UV‐Vis absorbance spectra collected during hot melt extrusion. Risks that impact the ability of the analytical procedure to measure piroxicam consistently were assessed using failure mode and effect analysis. The critical analytical attributes measured were colour (L* lightness, b* yellow to blue colour parameters—in‐process critical quality attributes) that are linked to the ability to measure the API content and transmittance. The method validation was based on the accuracy profile strategy and ICH Q2(R1) validation criteria. The accuracy profile obtained with two validation sets showed that the 95% β‐expectation tolerance limits for all piroxicam concentration levels analysed were within the combined trueness and precision acceptance limits set at ±5%. The method robustness was tested by evaluating the effects of screw speed (150–250 rpm) and feed rate (5–9 g/min) on piroxicam content around 15% w/w. In‐line UV‐Vis spectroscopy was shown to be a robust and practical PAT tool for monitoring the piroxicam content, a critical quality attribute in a pharmaceutical HME process

Biomedical Applications of Batteries

An overview is presented of the many ways in which batteries and battery materials are used in medicine and in biomedical studies. These include the use of batteries as power sources for motorised wheelchairs, surgical tools, cardiac pacemakers and defibrillators, dynamic prostheses, sensors and monitors for physiological parameters, neurostimulators, devices for pain relief, and iontophoretic, electroporative and related devices for drug administration. The various types of battery and fuel cell used for this wide range of applications will be considered, together with the potential harmful side effects, including accidental ingestion of batteries and the explosive nature of some of the early cardiac pacemaker battery systems

Pattern of cryospheric seismic events observed at Ekström ice shelf, Antarctica

Mobility of glaciers such as rapid retreat or disintegration of large ice volumes produces a large variety of different seismic signals. Thus, evaluating cryospheric seismic events (e.g. changes of their occurrence in space and time)allows to monitor glacier dynamics. We analyze a one year data span recorded at the Neumayer seismic network in Antarctica. Events are automatically recognized using hidden Markov models. In this study we focused on a specifc event type occurring close to the grounding line of the Ekström ice shelf. Observed waveform characteristics are consistent with an initial fracturing followed by the resonance of a water filled cavity resulting in a so-called hybrid event. The number of events detected strongly correlates with dominant tide periods. We assume the cracking to be driven by existing glacier stresses through bending. Voids are then filled by sea water, exciting the observed resonance. In agreement with this model, events occur almost exclusively during rising tides where cavities are opened at the bottom of the glacier, i.e. at the sea/ice interface

Effusive and explosive volcanism on the ultraslow-spreading Gakkel Ridge, 85°E

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 13 (2012): Q10005, doi:10.1029/2012GC004187.We use high-definition seafloor digital imagery and multibeam bathymetric data acquired during the 2007 Arctic Gakkel Vents Expedition (AGAVE) to evaluate the volcanic characteristics of the 85°E segment of the ultraslow spreading Gakkel Ridge (9 mm yr−1 full rate). Our seafloor imagery reveals that the axial valley is covered by numerous, small-volume (order ~1000 m3) lava flows displaying a range of ages and morphologies as well as unconsolidated volcaniclastic deposits with thicknesses up to 10 cm. The valley floor contains two prominent volcanic lineaments made up of axis-parallel ridges and small, cratered volcanic cones. The lava flows appear to have erupted from a number of distinct source vents within the ~12–15 km-wide axial valley. Only a few of these flows are fresh enough to have potentially erupted during the 1999 seismic swarm at this site, and these are associated with the Oden and Loke volcanic cones. We model the widespread volcaniclastic deposits we observed on the seafloor as having been generated by the explosive discharge of CO2 that accumulated in (possibly deep) crustal melt reservoirs. The energy released during explosive discharge, combined with the buoyant rise of hot fluid, lofted fragmented clasts of rapidly cooling magma into the water column, and they subsequently settled onto the seafloor as fall deposits surrounding the source vent.We gratefully acknowledge the financial support of the National Aeronautics and Space Administration, the National Science Foundation (N.S.F.), the International Polar Year 2007–2008, and Woods Hole Oceanographic Institution; and the graduate support provided by N.S.F., the NDSEG Fellowship, and WHOI Deep Ocean Exploration Institute.2013-04-0

Imaging crustal structure in South-Central Costa Rica with Receiver Functions

An array of broadband seismometers transecting the Talamanca Range in southern Costa Rica was operated from 2005 until 2007. In combination with data from a short‐period network near Quepos in central Costa Rica, this data is analyzed by the receiver function method to image the crustal structure in south‐central Costa Rica. Two strong positive signals are seen in the migrated images, interpreted as the Moho (at around 35 km depth) and an intra‐crustal discontinuity (15 km depth). A relatively flat crustal and Moho interface underneath the north‐east flank of the Talamanca Range can be followed for a lateral distance of about 50 km parallel to the trench, with only slight changes in the overall geometry. Closer to the coast, the topography of the discontinuities shows several features, most notably a deeper Moho underneath the Talamanca Mountain Range and volcanic arc. Under the highest part of the mountain ranges, the Moho reaches a depth of about 50 km, which indicates that the mountain ranges are approximately isostatically compensated. Local deviations from the crustal thickness expected for isostatic equilibrium occur under the active volcanic arc and in south Costa Rica. In the transition region between the active volcanic arc and the Talamanca Range, both the Moho and intracrustal discontinuity appear distorted, possibly related to the southern edge of the active volcanic zone and deformation within the southern part of the Central Costa Rica Deformed Belt. Near the volcanoes Irazu and Turrialba, a shallow converter occurs, correlating with a low‐velocity, low‐density body seen in tomography and gravimetry. Applying a grid search for the crustal interface depth and vp/vs ratio cannot constrain vp/vs values well, but points to generally low values (<1.7) in the upper crust. This is consistent with quartz‐rich rocks forming the mountain range

The steeply subducting edge of the Cocos Ridge : evidence from receiver functions beneath the northern Talamanca Range, south-central Costa Rica

The deep structure of the south-central Costa Rican subduction zone has not been studied in great detail so far because large parts of the area are virtually inaccessible. We present a receiver function study along a transect of broadband seismometers through the northern flank of the Cordillera de Talamanca (south Costa Rica). Below Moho depths, the receiver functions image a dipping positive conversion signal. This is interpreted as the subducting Cocos Plate slab, compatible with the conversions in the individual receiver functions. In finite difference modeling, a dipping signal such as the one imaged can only be reproduced by a steeply (80°) dipping structure present at least until a depth of about 70–100 km; below this depth, the length of the slab cannot be determined because of possible scattering effects. The proposed position of the slab agrees with previous results from local seismicity, local earthquake tomography, and active seismic studies, while extending the slab location to greater depths and steeper dip angle. Along the trench, no marked change is observed in the receiver functions, suggesting that the steeply dipping slab continues until the northern flank of the Cordillera de Talamanca, in the transition region between the incoming seamount segment and Cocos Ridge. Considering the time predicted for the establishment of shallow angle underthrusting after the onset of ridge collision, the southern Costa Rican subduction zone may at present be undergoing a reconfiguration of subduction style, where the transition to shallow underthrusting may be underway but still incomplete