Requirements for the Production of Microtablets: Suitability of Direct-Compression Excipients Estimated from Powder Characteristics and Flow Rates

Eleven direct-compression excipients, namely 3 microcrystalline celluloses, 4 lactoses, 4 co-processed excipients, and 4 mixtures of lactoses with Avicel PHI02 SCG were evaluated for possible use in micro tableting. Powder-technological parameters, namely particle size distributions, true and apparent densities, densification behaviour, and mass flow rates from a funnel through very narrow orifices, were determined.

Flow rates required on modern high-speed rotary tableting machines were calculated.

Flow rates may be estimated even for very narrow orifices, and such studies aid in selection of suitable excipients.

Mainly spray-dried lactose preparations with certain, definite upper limits in size distribution, seem to comply with the prerequisites for the production of micro tablets.     

Schizophrenia is associated with altered orienting activity: Depression with electrodermal (cholinergic?) deficit and normal orienting response.

The import of a recent consensus that a distinctive subgroup of schizophrenics is marked by nonreactivity of the orienting response (OR) to innocuous stimuli has been made ambiguous by reports of similar nonreactivity among depressives. To test this, we studied 50 schizophrenics (14 drug free), 50 depressives (20 drug free), and 50 normal controls. Stimuli were 1000 Hz (60 dB) or 2000 Hz (58 dB) 1-s tones delivered either to the left or right ear. A subsample of each group was told they need do nothing during tone presentations (habituation series); other subsamples had to press a pedal for each designated target signal (left ear, right ear, 1000 Hz, 2000 Hz), ignoring all nontarget tones. Skin conductance response (SCR) and finger pulse volume (FPV) analyses are reported. As in previous work, schizophrenics showed high nonresponding in the habituation series, consistent in both SCR and FPV, and they showed normalizing in both to target signals. Depressives were equally nonresponsive during the habituation series in SCR, but did not normalize to target signals and showed normal FPV response during both the habituation and target series. Whereas schizophrenic dysfunction reflected OR change, that of depressives seemed to reflect cholinergic deficit but intact OR. This was associated with high retardation and low agitation ratings, but not with degree of depression on Hamilton or Zung scales. In addition, 10 largely remitted depressives showed the same pattern as did patients currently in a major depressive episode. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of Preoxidation on High-Temperature Corrosion of a FeCrAl Alloy Under Conditions Relevant to Biomass Firing

Preoxidation of a commercial FeCrAl alloy (Kanthal APM) was evaluated as a surface modification approach to reduce alkali chloride-induced corrosion during biomass firing in power plants. Samples of the alloy preoxidized at 900 °C in O₂ or O₂ + 10 vol% H₂O, and at 1100 °C in O₂, were coated with KCl and exposed at 560 °C to a gas mixture comprising of 12 vol% CO₂, 6 vol% O₂, 3 vol% H₂O, 400 ppmv HCl and 60 ppmv SO₂. The oxide formed at 1100 °C showed no reactivity with the corrosive species. By contrast, all samples preoxidized at 900 °C suffered severe attack, resulting in formation of Fe-, Cr- and Al-containing corrosion products in a heterogeneous morphology, similar to non-preoxidized samples. The observed differences with respect to the degree of corrosion attack on the preoxidized samples are discussed in terms of the composition and thickness of the different types of Al₂O₃ layers obtained by the preoxidation treatment.     

Engineered morphologies of layered double hydroxide nanoarchitectured shell microspheres and their calcined products

CoFe^IIFe^III-layered double hydroxide (LDH) hollow spheres with two distinctly different hierarchical morphologies—flower-like and raspberry-like, involving edge-on and face-on oriented LDH platelets as building blocks, respectively—can be fabricated by tuning the rate of addition of NaOH solution in a coprecipitation process with sulfonated polystyrene spheres as a template. Ex situ pH-dependent microscopic observations of the formation of the flower-like LDH shells shows the details of non-classic nucleation and growth underlying the edge-on orientation. After calcination, the resulting CoFe₂O₄ materials retain the hierarchical morphology of the corresponding LDH precursor. The hollow CoFe₂O₄ spheres with raspberry-like morphology exhibit magnetic properties comparable to a reference material obtained by calcination of a conventional LDH powder precursor. Similar materials with tunable magnetic properties can be prepared by virtue of the flexibility in LDH layer composition. The CoFe^IIFe^III-LDH spheres with a raspberry-like morphology may be also be prepared by using a scalable procedure involving separate ultra-rapid nucleation and aging steps in a modified colloid mill reactor. The results reported here may open up the possibility of producing shell structures with controllable morphologies and properties on a large scale.     

In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung—A dialog between aerosol science and biology

The introduction of engineered nanostructured materials into a rapidly increasing number of industrial and consumer products will result in enhanced exposure to engineered nanoparticles. Workplace exposure has been identified as the most likely source of uncontrolled inhalation of engineered aerosolized nanoparticles, but release of engineered nanoparticles may occur at any stage of the lifecycle of (consumer) products. The dynamic development of nanomaterials with possibly unknown toxicological effects poses a challenge for the assessment of nanoparticle induced toxicity and safety.In this consensus document from a workshop on in-vitro cell systems for nanoparticle toxicity testing¹ an overview is given of the main issues concerning exposure to airborne nanoparticles, lung physiology, biological mechanisms of (adverse) action, in-vitro cell exposure systems, realistic tissue doses, risk assessment and social aspects of nanotechnology. The workshop participants recognized the large potential of in-vitro cell exposure systems for reliable, high-throughput screening of nanoparticle toxicity. For the investigation of lung toxicity, a strong preference was expressed for air–liquid interface (ALI) cell exposure systems (rather than submerged cell exposure systems) as they more closely resemble in-vivo conditions in the lungs and they allow for unaltered and dosimetrically accurate delivery of aerosolized nanoparticles to the cells. An important aspect, which is frequently overlooked, is the comparison of typically used in-vitro dose levels with realistic in-vivo nanoparticle doses in the lung. If we consider average ambient urban exposure and occupational exposure at 5 mg/m³ (maximum level allowed by Occupational Safety and Health Administration (OSHA)) as the boundaries of human exposure, the corresponding upper-limit range of nanoparticle flux delivered to the lung tissue is 3×10^?5–5×10^-3 μg/h/cm² of lung tissue and 2–300 particles/h/(epithelial) cell. This range can be easily matched and even exceeded by almost all currently available cell exposure systems.The consensus statement includes a set of recommendations for conducting in-vitro cell exposure studies with pulmonary cell systems and identifies urgent needs for future development. As these issues are crucial for the introduction of safe nanomaterials into the marketplace and the living environment, they deserve more attention and more interaction between biologists and aerosol scientists. The members of the workshop believe that further advances in in-vitro cell exposure studies would be greatly facilitated by a more active role of the aerosol scientists. The technical know-how for developing and running ALI in-vitro exposure systems is available in the aerosol community and at the same time biologists/toxicologists are required for proper assessment of the biological impact of nanoparticles.     

Expert elicitation on ultrafine particles: likelihood of health effects and causal pathways

Background

Exposure to fine ambient particulate matter (PM) has consistently been associated with increased morbidity and mortality. The relationship between exposure to ultrafine particles (UFP) and health effects is less firmly established. If UFP cause health effects independently from coarser fractions, this could affect health impact assessment of air pollution, which would possibly lead to alternative policy options to be considered to reduce the disease burden of PM. Therefore, we organized an expert elicitation workshop to assess the evidence for a causal relationship between exposure to UFP and health endpoints.

Methods

An expert elicitation on the health effects of ambient ultrafine particle exposure was carried out, focusing on: 1) the likelihood of causal relationships with key health endpoints, and 2) the likelihood of potential causal pathways for cardiac events. Based on a systematic peer-nomination procedure, fourteen European experts (epidemiologists, toxicologists and clinicians) were selected, of whom twelve attended. They were provided with a briefing book containing key literature. After a group discussion, individual expert judgments in the form of ratings of the likelihood of causal relationships and pathways were obtained using a confidence scheme adapted from the one used by the Intergovernmental Panel on Climate Change.

Results

The likelihood of an independent causal relationship between increased short-term UFP exposure and increased all-cause mortality, hospital admissions for cardiovascular and respiratory diseases, aggravation of asthma symptoms and lung function decrements was rated medium to high by most experts. The likelihood for long-term UFP exposure to be causally related to all cause mortality, cardiovascular and respiratory morbidity and lung cancer was rated slightly lower, mostly medium. The experts rated the likelihood of each of the six identified possible causal pathways separately. Out of these six, the highest likelihood was rated for the pathway involving respiratory inflammation and subsequent thrombotic effects.

Conclusion

The overall medium to high likelihood rating of causality of health effects of UFP exposure and the high likelihood rating of at least one of the proposed causal mechanisms explaining associations between UFP and cardiac events, stresses the importance of considering UFP in future health impact assessments of (transport-related) air pollution, and the need for further research on UFP exposure and health effects.     

Electrospun polystyrene fibers containing high temperature stable volatile fragrance/flavor facilitated by cyclodextrin inclusion complexes

In this study, we report on electrospinning of functional polystyrene (PS) fibers containing cyclodextrin-menthol inclusion complexes (CD-menthol-ICs). Our goal is to develop functional electrospun fibers containing fragrances/flavors with enhanced durability and stability assisted by cyclodextrin inclusion complexation. We have used menthol as a model fragrance/flavor material and CD-menthol-ICs were incorporated in electrospun PS fiber by using three types of CDs; α-CD, β-CD and γ-CD. Due to complexation of menthol with CDs, we observed that the stabilization of menthol was achieved up to 350 °C for all the PS/CD-menthol-IC webs whereas the PS fibers without the CD complex could not preserve volatile menthol molecules. In addition, γ-CD was more effective for the stabilization and release of menthol at a broad temperature range (100–350 °C) when compared to α-CD and β-CD. This study suggested that the electrospun fibers functionalized with CD-ICs are very effective for enhancing the temperature stability of volatile fragrances/flavors and therefore show potentials for the development of functional fibrous materials.     

Discovery of Ligands for the Human Intestinal Di‐/Tripeptide Transporter (hPEPT1) Using a QSAR‐Assisted Virtual Screening Strategy

The discovery of novel ligands for the hPEPT1 transporter is reported. By exploiting a fast and rigorously validated QSAR model in combination with the distance in activity‐centered chemical space (DACCS) approach, a database of commercially available compounds (Sigma–Aldrich) was screened for virtual hits. Twelve compounds were then purchased and characterized in an apical [¹⁴C]Gly‐Sar uptake competition assay. Four compounds displayed affinity in the medium‐to‐high range. A simple benzophenone derivative displayed high affinity with a sub‐millimolar binding constant (K_i=0.24 mM ). The results of this study will serve as starting points for future projects, including the design and synthesis of compound libraries that seek to systematically explore the fundamental requirements for binding and transport by hPEPT1.