A systematic and mechanistic evaluation of aspartic acid as filler for directly compressed tablets containing trimethoprim and trimethoprim aspartate

The generally accepted paradigm of 'inert' and 'mono functional' excipient in dosage form has been recently challenged with the development of individual excipients capable of exhibiting multiple functions (e.g. binder-disintegrants, surfactant which affect P-gp function). The proposed study has been designed within the realm of multifunctionality and is the first and novel investigation towards evaluation of aspartic acid as a filler and disintegration enhancing agent for the delivery of biopharmaceutical class IV model drug trimethoprim. The study investigated powder characteristics using angle of repose, laser diffractometry and scanning electron microscopy (SEM). The prepared tablets were characterised using Heckel analysis, disintegration time and tensile strength measurements. Although Heckel analysis revealed that both TMP and TMP aspartate salt have high elasticity, the salt form produced a stronger compact which was attributed to the formation of agglomerates. Aspartic acid was found to have high plasticity, but its incorporation into the formulations was found to have a negative impact on the compaction properties of TMP and its salt. Surface morphology investigations showed that mechanical interlocking plays a vital role in binding TMP crystals together during compaction, while the small particle size of TMP aspartate agglomerates was found to have significant impact on the tensile strength of the tablets. The study concluded that aspartic acid can be employed as filler and disintegrant and that compactability within tablets was independent of the surface charge of the excipients.

Size-controlled TiO2 nanoparticles on porous hosts for enhanced photocatalytic hydrogen production

Nanocystalline TiO2 particles were successfully synthesized on porous hosts (SBA-15 and ZSM-15) via a sol-gel impregnation method. Resulting nanocomposites were characterized by XRD, TEM, BET surface analysis, Raman and UV-vis diffuse reflectance spectroscopy, and their photocatalytic activity for H2 production evaluated. XRD evidences the formation of anatase nanoparticles over both ZSM-5 and SBA-15 porous supports, with TEM highlighting a strong particle size dependence on titania precursor concentration. Photocatalytic activities of TiO2/ZSM-5 and TiO2/SBA-15 composites were significantly enhanced compared to pure TiO2, owing to the smaller TiO2 particle size and higher surface area of the former. TiO2 loadings over the porous supports and concomitant photocatalytic hydrogen production were optimized with respect to light absorption, available surface reaction sites and particle size. 10%TiO2/ZSM-5 and 20%TiO2/SBA-15 proved the most active photocatalysts, exhibiting extraordinary hydrogen evolution rates of 10,000 and 8800μmolgTiO2 -1 h-1 under full arc, associated with high external quantum efficiencies of 12.6% and 5.4% respectively under 365nm irradiation.

Unfolding grain size effects in barium titanate ferroelectric ceramics

Grain size effects on the physical properties of polycrystalline ferroelectrics have been extensively studied for decades; however there are still major controversies regarding the dependence of the piezoelectric and ferroelectric properties on the grain size. Dense BaTiO3 ceramics with different grain sizes were fabricated by either conventional sintering or spark plasma sintering using micro- and nano-sized powders. The results show that the grain size effect on the dielectric permittivity is nearly independent of the sintering method and starting powder used. A peak in the permittivity is observed in all the ceramics with a grain size near 1μm and can be attributed to a maximum domain wall density and mobility. The piezoelectric coefficient d33 and remnant polarization Pr show diverse grain size effects depending on the particle size of the starting powder and sintering temperature. This suggests that besides domain wall density, other factors such as back fields and point defects, which influence the domain wall mobility, could be responsible for the different grain size dependence observed in the dielectric and piezoelectric/ferroelectric properties. In cases where point defects are not the dominant contributor, the piezoelectric constant d33 and the remnant polarization Pr increase with increasing grain size.

Validation of a multi-component digital dissolution model for irregular particles

A new mesoscale simulation model for solids dissolution based on an computationally efficient and versatile digital modelling approach (DigiDiss) is considered and validated against analytical solutions and published experimental data for simple geometries. As the digital model is specifically designed to handle irregular shapes and complex multi-component structures, use of the model is explored for single crystals (sugars) and clusters. Single crystals and the cluster were first scanned using X-ray microtomography to obtain a digital version of their structures. The digitised particles and clusters were used as a structural input to digital simulation. The same particles were then dissolved in water and the dissolution process was recorded by a video camera and analysed yielding: the overall dissolution times and images of particle size and shape during the dissolution. The results demonstrate the coherence of simulation method to reproduce experimental behaviour, based on known chemical and diffusion properties of constituent phase. The paper discusses how further sophistications to the modelling approach will need to include other important effects such as complex disintegration effects (particle ejection, uncertainties in chemical properties). The nature of the digital modelling approach is well suited to for future implementation with high speed computation using hybrid conventional (CPU) and graphical processor (GPU) systems.

A holistic multi evidence approach to study the fragmentation behaviour of crystalline mannitol

Mannitol is an essential excipient employed in orally disintegrating tablets due to its high palatability. However its fundamental disadvantage is its fragmentation during direct compression, producing mechanically weak tablets. The primary aim of this study was to assess the fracture behaviour of crystalline mannitol in relation to the energy input during direct compression, utilising ball milling as the method of energy input, whilst assessing tablet characteristics of post-milled powders. Results indicated that crystalline mannitol fractured at the hydrophilic (011) plane, as observed through SEM, alongside a reduction in dispersive surface energy. Disintegration times of post-milled tablets were reduced due to the exposure of the hydrophilic plane, whilst more robust tablets were produced. This was shown through higher tablet hardness and increased plastic deformation profiles of the post-milled powders, as observed with a lower yield pressure through an out-of-die Heckel analysis. Evaluation of crystal state using x-ray diffraction/differential scanning calorimetry showed that mannitol predominantly retained the β-polymorph; however x-ray diffraction provided a novel method to calculate energy input into the powders during ball milling. It can be concluded that particle size reduction is a pragmatic strategy to overcome the current limitation of mannitol fragmentation and provide improvements in tablet properties.

Quantitative determination of carbonaceous particle mixing state in Paris using single-particle mass spectrometer and aerosol mass spectrometer measurements

Single-particle mixing state information can be a powerful tool for assessing the relative impact of local and regional sources of ambient particulate matter in urban environments. However, quantitative mixing state data are challenging to obtain using single-particle mass spectrometers. In this study, the quantitative chemical composition of carbonaceous single particles has been determined using an aerosol time-of-flight mass spectrometer (ATOFMS) as part of the MEGAPOLI 2010 winter campaign in Paris, France. Relative peak areas of marker ions for elemental carbon (EC), organic aerosol (OA), ammonium, nitrate, sulfate and potassium were compared with concurrent measurements from an Aerodyne high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS), a thermal-optical OCEC analyser and a particle into liquid sampler coupled with ion chromatography (PILS-IC). ATOFMS-derived estimated mass concentrations reproduced the variability of these species well (R-2 = 0.67-0.78), and 10 discrete mixing states for carbonaceous particles were identified and quantified. The chemical mixing state of HR-ToF-AMS organic aerosol factors, resolved using positive matrix factorisation, was also investigated through comparison with the ATOFMS dataset. The results indicate that hydrocarbon-like OA (HOA) detected in Paris is associated with two EC-rich mixing states which differ in their relative sulfate content, while fresh biomass burning OA (BBOA) is associated with two mixing states which differ significantly in their OA/EC ratios. Aged biomass burning OA (OOA(2)-BBOA) was found to be significantly internally mixed with nitrate, while secondary, oxidised OA (OOA) was associated with five particle mixing states, each exhibiting different relative secondary inorganic ion content. Externally mixed secondary organic aerosol was not observed. These findings demonstrate the range of primary and secondary organic aerosol mixing states in Paris. Examination of the temporal behaviour and chemical composition of the ATOFMS classes also enabled estimation of the relative contribution of transported emissions of each chemical species and total particle mass in the size range investigated. Only 22% of the total ATOFMS-derived particle mass was apportioned to fresh, local emissions, with 78% apportioned to regional/continental-scale emissions. Single-particle mixing state information can be a powerful tool for assessing the relative impact of local and regional sources of ambient particulate matter in urban environments. However, quantitative mixing state data are challenging to obtain using single-particle mass spectrometers. In this study, the quantitative chemical composition of carbonaceous single particles has been determined using an aerosol time-of-flight mass spectrometer (ATOFMS) as part of the MEGAPOLI 2010 winter campaign in Paris, France. Relative peak areas of marker ions for elemental carbon (EC), organic aerosol (OA), ammonium, nitrate, sulfate and potassium were compared with concurrent measurements from an Aerodyne high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS), a thermal-optical OCEC analyser and a particle into liquid sampler coupled with ion chromatography (PILS-IC). ATOFMS-derived estimated mass concentrations reproduced the variability of these species well (R-2 = 0.67-0.78), and 10 discrete mixing states for carbonaceous particles were identified and quantified. The chemical mixing state of HR-ToF-AMS organic aerosol factors, resolved using positive matrix factorisation, was also investigated through comparison with the ATOFMS dataset. The results indicate that hydrocarbon-like OA (HOA) detected in Paris is associated with two EC-rich mixing states which differ in their relative sulfate content, while fresh biomass burning OA (BBOA) is associated with two mixing states which differ significantly in their OA/EC ratios. Aged biomass burning OA (OOA(2)-BBOA) was found to be significantly internally mixed with nitrate, while secondary, oxidised OA (OOA) was associated with five particle mixing states, each exhibiting different relative secondary inorganic ion content. Externally mixed secondary organic aerosol was not observed. These findings demonstrate the range of primary and secondary organic aerosol mixing states in Paris. Examination of the temporal behaviour and chemical composition of the ATOFMS classes also enabled estimation of the relative contribution of transported emissions of each chemical species and total particle mass in the size range investigated. Only 22% of the total ATOFMS-derived particle mass was apportioned to fresh, local emissions, with 78% apportioned to regional/continental-scale emissions.

Sources and mixing state of size-resolved elemental carbon particles in a European megacity: Paris

An Aerosol Time-Of-Flight Mass Spectrometer (ATOFMS) was deployed to investigate the size-resolved chemical composition of single particles at an urban background site in Paris, France, as part of the MEGAPOLI winter campaign in January/February 2010. ATOFMS particle counts were scaled to match coincident Twin Differential Mobility Particle Sizer (TDMPS) data in order to generate hourly size-resolved mass concentrations for the single particle classes observed. The total scaled ATOFMS particle mass concentration in the size range 150–1067 nm was found to agree very well with the sum of concurrent High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) and Multi-Angle Absorption Photometer (MAAP) mass concentration measurements of organic carbon (OC), inorganic ions and black carbon (BC) (R2 = 0.91). Clustering analysis of the ATOFMS single particle mass spectra allowed the separation of elemental carbon (EC) particles into four classes: (i) EC attributed to biomass burning (ECbiomass), (ii) EC attributed to traffic (ECtraffic), (iii) EC internally mixed with OC and ammonium sulfate (ECOCSOx), and (iv) EC internally mixed with OC and ammonium nitrate (ECOCNOx). Average hourly mass concentrations for EC-containing particles detected by the ATOFMS were found to agree reasonably well with semi-continuous quantitative thermal/optical EC and optical BC measurements (r2 = 0.61 and 0.65–0.68 respectively, n = 552). The EC particle mass assigned to fossil fuel and biomass burning sources also agreed reasonably well with BC mass fractions assigned to the same sources using seven-wavelength aethalometer data (r2 = 0.60 and 0.48, respectively, n = 568). Agreement between the ATOFMS and other instrumentation improved noticeably when a period influenced by significantly aged, internally mixed EC particles was removed from the intercomparison. 88% and 12% of EC particle mass was apportioned to fossil fuel and biomass burning respectively using the ATOFMS data compared with 85% and 15% respectively for BC estimated from the aethalometer model. On average, the mass size distribution for EC particles is bimodal; the smaller mode is attributed to locally emitted, mostly externally mixed EC particles, while the larger mode is dominated by aged, internally mixed ECOCNOx particles associated with continental transport events. Periods of continental influence were identified using the Lagrangian Particle Dispersion Model (LPDM) "FLEXPART". A consistent minimum between the two EC mass size modes was observed at approximately 400 nm for the measurement period. EC particles below this size are attributed to local emissions using chemical mixing state information and contribute 79% of the scaled ATOFMS EC particle mass, while particles above this size are attributed to continental transport events and contribute 21% of the EC particle mass. These results clearly demonstrate the potential benefit of monitoring size-resolved mass concentrations for the separation of local and continental EC emissions. Knowledge of the relative input of these emissions is essential for assessing the effectiveness of local abatement strategies.

Source apportionment of PM2.5 in Cork Harbour, Ireland using a combination of single particle mass spectrometry and quantitative semi-continuous measurements

An aerosol time-of-flight mass spectrometer (ATOFMS) was deployed for the measurement of the size resolved chemical composition of single particles at a site in Cork Harbour, Ireland for three weeks in August 2008. The ATOFMS was co-located with a suite of semi-continuous instrumentation for the measurement of particle number, elemental carbon (EC), organic carbon (OC), sulfate and particulate matter smaller than 2.5 μm in diameter (PM2.5). The temporality of the ambient ATOFMS particle classes was subsequently used in conjunction with the semi-continuous measurements to apportion PM2.5 mass using positive matrix factorisation. The synergy of the single particle classification procedure and positive matrix factorisation allowed for the identification of six factors, corresponding to vehicular traffic, marine, long-range transport, various combustion, domestic solid fuel combustion and shipping traffic with estimated contributions to the measured PM2.5 mass of 23%, 14%, 13%, 11%, 5% and 1.5% respectively. Shipping traffic was found to contribute 18% of the measured particle number (20–600 nm mobility diameter), and thus may have important implications for human health considering the size and composition of ship exhaust particles. The positive matrix factorisation procedure enabled a more refined interpretation of the single particle results by providing source contributions to PM2.5 mass, while the single particle data enabled the identification of additional factors not possible with typical semi-continuous measurements, including local shipping traffic.

Chemistry and grain-size distribution of terrigenous sediments deposited at Site GeoB9501

The Sahara Desert is the largest source of mineral dust in the world. Emissions of African dust increased sharply in the early 1970s, a change that has been attributed mainly to drought in the Sahara/Sahel region caused by changes in the global distribution of sea surface temperature. The human contribution to land degradation and dust mobilization in this region remains poorly understood, owing to the paucity of data that would allow the identification of long-term trends in desertification. Direct measurements of airborne African dust concentrations only became available in the mid-1960s from a station on Barbados and subsequently from satellite imagery since the late 1970s: they do not cover the onset of commercial agriculture in the Sahel region ~170 years ago. Here we construct a 3,200-year record of dust deposition off northwest Africa by investigating the chemistry and grain-size distribution of terrigenous sediments deposited at a marine site located directly under the West African dust plume. With the help of our dust record and a proxy record for West African precipitation we find that, on the century scale, dust deposition is related to precipitation in tropical West Africa until the seventeenth century. At the beginning of the nineteenth century, a sharp increase in dust deposition parallels the advent of commercial agriculture in the Sahel region. Our findings suggest that human-induced dust emissions from the Sahel region have contributed to the atmospheric dust load for about 200 years.

He isotope, U/Th isotope, Calcium carbonate, biogenic opal, rare earth element concentrations, and grain size distribution measured on core-top sediments during SONNE cruise SO202 (INOPEX)

Eolian dust is a significant source of iron and other nutrients that are essential for the health of marine ecosystems and potentially a controlling factor of the high nutrient-low chlorophyll status of the Subarctic North Pacific. We map the spatial distribution of dust input using three different geochemical tracers of eolian dust, 4He, 232Th and rare earth elements, in combination with grain size distribution data, from a set of core-top sediments covering the entire Subarctic North Pacific. Using the suite of geochemical proxies to fingerprint different lithogenic components, we deconvolve eolian dust input from other lithogenic inputs such as volcanic ash, ice-rafted debris, riverine and hemipelagic input. While the open ocean sites far away from the volcanic arcs are dominantly composed of pure eolian dust, lithogenic components other than eolian dust play a more crucial role along the arcs. In sites dominated by dust, eolian dust input appears to be characterized by a nearly uniform grain size mode at ~4 µm. Applying the 230Th-normalization technique, our proxies yield a consistent pattern of uniform dust fluxes of 1-2 g/m**2/yr across the Subarctic North Pacific. Elevated eolian dust fluxes of 2-4 g/m**2/yr characterize the westernmost region off Japan and the southern Kurile Islands south of 45° N and west of 165° E along the main pathway of the westerly winds. The core-top based dust flux reconstruction is consistent with recent estimates based on dissolved thorium isotope concentrations in seawater from the Subarctic North Pacific. The dust flux pattern compares well with state-of-the-art dust model predictions in the western and central Subarctic North Pacific, but we find that dust fluxes are higher than modeled fluxes by 0.5-1 g/m**2/yr in the northwest, northeast and eastern Subarctic North Pacific. Our results provide an important benchmark for biogeochemical models and a robust approach for downcore studies testing dust-induced iron fertilization of past changes in biological productivity in the Subarctic North Pacific.

San Francisco Coastal System grain size and geochemical data for sand provenance study

Over 150 million cubic meter of sand-sized sediment has disappeared from the central region of the San Francisco Bay Coastal System during the last half century. This enormous loss may reflect numerous anthropogenic influences, such as watershed damming, bay-fill development, aggregate mining, and dredging. The reduction in Bay sediment also appears to be linked to a reduction in sediment supply and recent widespread erosion of adjacent beaches, wetlands, and submarine environments. A unique, multi-faceted provenance study was performed to definitively establish the primary sources, sinks, and transport pathways of beach sized-sand in the region, thereby identifying the activities and processes that directly limit supply to the outer coast. This integrative program is based on comprehensive surficial sediment sampling of the San Francisco Bay Coastal System, including the seabed, Bay floor, area beaches, adjacent rock units, and major drainages. Analyses of sample morphometrics and biological composition (e.g., Foraminifera) were then integrated with a suite of tracers including 87Sr/86Sr and 143Nd/144Nd isotopes, rare earth elements, semi-quantitative X-ray diffraction mineralogy, and heavy minerals, and with process-based numerical modeling, in situ current measurements, and bedform asymmetry to robustly determine the provenance of beach-sized sand in the region.

Size-partitioned phytoplankton carbon concentrations retrieved from ocean color data, links to data in netCDF format

Owing to their important roles in biogeochemical cycles, phytoplankton functional types (PFTs) have been the aim of an increasing number of ocean color algorithms. Yet, none of the existing methods are based on phytoplankton carbon (C) biomass, which is a fundamental biogeochemical and ecological variable and the "unit of accounting" in Earth system models. We present a novel bio-optical algorithm to retrieve size-partitioned phytoplankton carbon from ocean color satellite data. The algorithm is based on existing methods to estimate particle volume from a power-law particle size distribution (PSD). Volume is converted to carbon concentrations using a compilation of allometric relationships. We quantify absolute and fractional biomass in three PFTs based on size - picophytoplankton (0.5-2 µm in diameter), nanophytoplankton (2-20 µm) and microphytoplankton (20-50 µm). The mean spatial distributions of total phytoplankton C biomass and individual PFTs, derived from global SeaWiFS monthly ocean color data, are consistent with current understanding of oceanic ecosystems, i.e., oligotrophic regions are characterized by low biomass and dominance of picoplankton, whereas eutrophic regions have high biomass to which nanoplankton and microplankton contribute relatively larger fractions. Global climatological, spatially integrated phytoplankton carbon biomass standing stock estimates using our PSD-based approach yield - 0.25 Gt of C, consistent with analogous estimates from two other ocean color algorithms and several state-of-the-art Earth system models. Satisfactory in situ closure observed between PSD and POC measurements lends support to the theoretical basis of the PSD-based algorithm. Uncertainty budget analyses indicate that absolute carbon concentration uncertainties are driven by the PSD parameter No which determines particle number concentration to first order, while uncertainties in PFTs' fractional contributions to total C biomass are mostly due to the allometric coefficients. The C algorithm presented here, which is not empirically constrained a priori, partitions biomass in size classes and introduces improvement over the assumptions of the other approaches. However, the range of phytoplankton C biomass spatial variability globally is larger than estimated by any other models considered here, which suggests an empirical correction to the No parameter is needed, based on PSD validation statistics. These corrected absolute carbon biomass concentrations validate well against in situ POC observations.

Grain size distribution and bulk chemistry of eolian dust

Atmospheric dust samples collected along a transect off the West African coast have been investigated for their physical (grain-size distribution), mineralogical, and chemical (major elements) composition. On the basis of these data the samples were grouped into sets of samples that most likely originated from the same source area. In addition, shipboard-collected atmospheric meteorological data, modeled 4-day back trajectories for each sampling day and location, and Total Ozone Mapping Spectrometer aerosol index data for the time period of dust collection (February-March 1998) were combined and used to reconstruct the sources of the groups of dust samples. On the basis of these data we were able to determine the provenance of the various dust samples. It appears that the bulk of the wind-blown sediments that are deposited in the proximal equatorial Atlantic Ocean are transported in the lower level (>~900 hPa) NE trade wind layer, which is a very dominant feature north of the Intertropical Convergence Zone (ITCZ). However, south of the surface expression of the ITCZ, down to 5°S, where surface winds are southwesterly, we still collected sediments that originated from the north and east, carried there by the NE trade wind layer, as well as by easterly winds from higher altitudes. The fact that the size of the wind-blown dust depends not only on the wind strength of the transporting agent but also on the distance to the source hampers a direct comparison of the dust's size distributions and measured wind strengths. However, a comparison between eolian dust and terrigenous sediments collected in three submarine sediment traps off the west coast of NW Africa shows that knowledge of the composition of eolian dust is a prerequisite for the interpretation of paleorecords obtained from sediment cores in the equatorial Atlantic.