Triboelectrification of Active Pharmaceutical Ingredients: Amines and Their Hydrochloride Salts.

The triboelectric properties of active pharmaceutical ingredients (APIs) contribute to problems during the manufacturing of pharmaceuticals. However, the triboelectric properties of APIs have not been comprehensively characterized. In this study, the effect of salt formulation on the triboelectric properties of APIs was investigated. The triboelectric properties of three groups of amines, namely tertiary amines, purine bases, and amino acids, and their hydrochlorides were evaluated using a suction-type Faraday cage meter. Most of the hydrochloride salts exhibited more negative charges than the corresponding free bases, and the degree by which the triboelectric property changed upon hydrochlorination depended on the structural groups of the compounds. In the case of tertiary amines, the change in the zero-charge margin upon hydrochlorination was negatively correlated with the zero-charge margin of the free base. In contrast, hydrochlorination of the amino acids led to a significant change in the zero-charge margin. In most cases, salt formation also affected the triboelectric properties of API powders. Controlling the triboelectric properties of APIs solves various problems caused by the electrification of raw material powders and granules during the production of pharmaceuticals, thereby increasing the quality of produced pharmaceuticals.

Antistatic treatment and salbutamol dosing have variable effect on drug delivery of valved holding chambers.

AIMS: Our aim was to evaluate whether the number of puffs or antistatic treatment have significant effect on drug delivery of six different valved holding chambers (VHCs). METHODS: We used simulated paediatric breathing pattern with 25/min frequency and 200 ml tidal volume. When comparing the effect of antistatic treatment, we used 100 µg of salbutamol (one puff Ventolin Evohaler 100 µg/dos) actuated into each VHC before and after detergent wash. When comparing the effect of one or two puffs (100 vs. 200 µg), all VHCs were washed prior to the measurements. RESULTS: All VHC were significantly affected by antistatic treatment. Washing improved drug delivery of four VHCs (1.3-2.2 fold increase in median filter dose) but had an opposite effect in two devices (54-61% decrease). The effect of dose doubling resulted in a 2.03-2.93 fold increase on filter dose in two VHCs. Four out of the six VHC showed significantly poorer performance with two puffs as opposed to one puff (ratio of two puffs to one puff varied between 1.19 and 1.77). CONCLUSION: VHCs marketed as antistatic are significantly affected by antistatic treatment. To ensure optimal drug delivery, salbutamol should be actuated to VHCs one puff at a time. Each VHC brand has its unique characteristic that affects drug delivery in a way that cannot be generalised to another VHC. There is a need for universal standardisation of VHCs. KEY NOTES: Valved holding chambers (VHCs) that are marketed as antistatic are significantly affected by antistatic treatment. Multiple actuations before inhalation tend to decrease the drug delivery efficacy of VHCs. Each VHC brand has its unique characteristic that affects drug delivery in a way that cannot be generalised to another VHC. There is a need for comprehensive and financially independent testing and standardisation of VHCs.

Electrostatic pollination by butterflies and moths.

Animals, most notably insects, generally seem to accumulate electrostatic charge in nature. These electrostatic charges will exert forces on other charges in these animals' environments and therefore have the potential to attract or repel other objects, for example, pollen from flowers. Here, we show that butterflies and moths (Lepidoptera) accumulate electrostatic charge while in flight. Then, using finite element analysis, we demonstrate that when within millimetres of a flower, the electrostatic charge of a lepidopteran generates an electric field in excess of 5 kV m-1, and that an electric field of this magnitude is sufficient to elicit contactless pollen transfer from flowers across air gaps onto the body of a butterfly or moth. Furthermore, we see that phylogenetic variations exist in the magnitude and polarity of net charge between different species and families and Lepidoptera. These phylogenetic variations in electrostatic charging correlate with morphological, biogeographical and ecological differences between different clades. Such correlations with biogeographical and ecological differences may reflect evolutionary adaptations towards maximizing or minimizing charge accumulation, in relation to pollination, predation and parasitism, and thus we introduce the idea that electrostatic charging may be a trait upon which evolution can act.

π-Hole bonding in a new co-crystal hydrate of gallic acid and pyrazine: static and dynamic charge density analysis.

A new cocrystal hydrate of gallic acid with pyrazine (4GA, Py, 4H2O; GA4PyW4) was obtained and characterized by single crystal X-ray diffraction. In addition to structure determination, experimental charge density analysis was carried out in terms of Multipole Modelling (MP), X-ray wavefunction refinement (XWR) and maximum entropy method (MEM). As a part of XWR, the structural refinement via Hirshfeld atom refinement was carried out and resulted in O-H bond lengths close to values from neutron diffraction. A systematic comparison of molecular conformations and aromatic interactions in this new cocrystal hydrate was performed with other existing polymorphs of gallic acid. In GA4PyW4, the two symmetry-independent gallic acid molecules have a syn COOH orientation and form the common (COOH)2 dimeric synthon. The carboxyl C atom displays the characteristics of π-holes with electropositive regions above and below the molecular plane and engages in acceptor-donor interactions with oxygen atoms of acidic O-H groups and phenol groups of neighbouring gallic acid molecules. The signature of the π-hole was identified from experimental charge density analysis, both in static density maps in MP and XWR as well as dynamic density in MEM, but it cannot be pinned down to a specific atom-atom interaction. This study presents the first comparison between an XWR and a MEM experimental electron-density determination.

The ecology of electricity and electroreception.

Electricity, the interaction between electrically charged objects, is widely known to be fundamental to the functioning of living systems. However, this appreciation has largely been restricted to the scale of atoms, molecules, and cells. By contrast, the role of electricity at the ecological scale has historically been largely neglected, characterised by punctuated islands of research infrequently connected to one another. Recently, however, an understanding of the ubiquity of electrical forces within the natural environment has begun to grow, along with a realisation of the multitude of ecological interactions that these forces may influence. Herein, we provide the first comprehensive collation and synthesis of research in this emerging field of electric ecology. This includes assessments of the role electricity plays in the natural ecology of predator-prey interactions, pollination, and animal dispersal, among many others, as well as the impact of anthropogenic activity on these systems. A detailed introduction to the ecology and physiology of electroreception - the biological detection of ecologically relevant electric fields - is also provided. Further to this, we suggest avenues for future research that show particular promise, most notably those investigating the recently discovered sense of aerial electroreception.

Maximized Hole Trapping in a Polystyrene Transistor Dielectric from a Highly Branched Iminobis(aminoarene) Side Chain.

We synthesized highly branched and electron-donating side chain subunits and attached them to polystyrene (PS) used as a dielectric layer in a pentacene field-effect transistor. The influence of these groups on dielectric function, charge retention, and threshold voltage shifts (ΔVth) depending on their positions in dielectric multilayers was determined. We compared the observations made on an N-perphenylated iminobisaniline side chain with those from the same side chains modified with ZnO nanoparticles and with an adduct formed from tetracyanoethylene (TCNE). We also synthesized an analogue in which six methoxy groups are present instead of two amine nitrogens. At 6 mol % side chain, hopping transport was sufficient to cause shorting of the gate, while at 2 mol %, charge trapping was observable as transistor threshold voltage shifts (ΔVth). We created three types of devices: with the substituted PS layer as single-layer dielectric, on top of a cross-linked PS layer but in contact with the pentacene (bilayers), and sandwiched between two PS layers in trilayers. Especially large bias stress effects and ΔVth, larger than those in the case of the hexamethoxy and previously studied dimethoxy analogues, were observed in the second case, and the effects increased with the increasing electron-donating properties of the modified side chains. The highest ΔVth was consistent with a majority of the side chains stabilizing the trapped charge. Trilayer devices showed decreased charge storage capability compared to previous work in which we used less donating side chains but in higher concentrations. The ZnO and TCNE modifications resulted in slightly more and less negative ΔVth, respectively, when the side chain polystyrene was not in contact with the pentacene and isolated from the gate electrode. The results indicate a likely maximum combination of molecular charge stabilizing activity and side chain concentration that still allows gate dielectric function.

Nonconductive Noncharging Composites: Tunable and Stretchable Materials for Adaptive Prevention of Charging by Contact Electrification.

Static charge generated by contact electrification can cause a wide range of undesirable consequences in our lives and in industry (e.g., adhesion of particles on surfaces, damage to electronics, and explosions). It has, however, been challenging to develop methods to prevent charging due to the vast types of materials that charge easily by contact electrification and the frequent changes in process and environmental conditions. The most common method is to use conductive materials for dissipating charge away; however, it is ineffective for many circumstances. Here, we propose a general and effective materials framework that involves a two-level consideration for preparing noncharging materials: (1) the variation of the proportion of a two-material composite and (2) the extent of stretching the composite material. This materials strategy is achieved by infusing particles within a stretchable bulk material. Importantly, the preparation of the noncharging surface for (1) is based on a novel fundamental mechanism that involves combining an appropriate amount of a material (e.g., the particles) that tends to charge positively with another material (e.g., the bulk material) that tends to charge negatively. This mechanism does not rely on conductivity; both the contacting materials naturally prevent the generation of static charge even when only nonconductive materials are involved. When the composite material is stretchable, the change in proportion of the surface coverage of the particles allows the charging response to be changed. Therefore, the variation in composition and stretching provide a wide two-dimensional parameter space for achieving noncharging response for the vast range of contacting materials that are used in industry and our lives. In addition, stretchability allows the composite material to flexibly adapt to changes in process and environmental conditions. This stretchable composite material was also demonstrated to be capable of preventing the adhesion of particles and separating particles of different materials.

A Measurement and Modeling Study of Hair Partition of Neutral, Cationic, and Anionic Chemicals.

Various neutral, cationic, and anionic chemicals contained in hair care products can be absorbed into hair fiber to modulate physicochemical properties such as color, strength, style, and volume. For environmental safety, there is also an interest in understanding hair absorption to wide chemical pollutants. There have been very limited studies on the absorption properties of chemicals into hair. Here, an experimental and modeling study has been carried out for the hair-water partition of a range of neutral, cationic, and anionic chemicals at different pH. The data showed that hair-water partition not only depends on the hydrophobicity of the chemical but also the pH. The partition of cationic chemicals to hair increased with pH, and this is due to their electrostatic interaction with hair increased from repulsion to attraction. For anionic chemicals, their hair-water partition coefficients decreased with increasing pH due to their electrostatic interaction with hair decreased from attraction to repulsion. Increase in pH did not change the partition of neutral chemicals significantly. Based on the new physicochemical insight of the pH effect on hair-water partition, a new quantitative structure property relationship model has been proposed, taking into account of both the hydrophobic interaction and electrostatic interaction of chemical with hair fiber.

Role of Phosphatidylserine-Derived Negative Surface Charges in the Recognition and Uptake of Intravenously Injected B16BL6-Derived Exosomes by Macrophages.

Exosomes are cell-derived extracellular vesicles that function as intercellular delivery carriers. Our previous study demonstrated that macrophages in the liver contributed to the rapid clearance of intravenously administered B16BL6-derived exosomes from the systemic circulation in mice. Phosphatidylserine (PS) may be responsible for this clearance because it is exposed on the surface of exosomes and is recognized by macrophages. In this study, the role of PS exposed on the membranes of exosomes in the uptake of B16BL6-derived exosomes by macrophages was investigated. Negatively charged PS- or phosphatidylglycerol-loaded liposomes suppressed the cellular uptake of PKH67-labeled exosomes by macrophages, whereas phosphatidylcholine-containing liposome did not affect uptake. Subsequently, for the in vivo analysis, exosomes were labeled with Gaussia luciferase, a reporter protein, or (3-125I-iodobenzoyl)norbiotinamide using exosome-tropic fusion proteins comprising the exosome-tropic protein lactadherin. The blood clearance of Gaussia luciferase-labeled exosomes after intravenous injection into mice was significantly delayed by the preinjection of PS- or phosphatidylglycerol-containing liposomes. Moreover, the accumulation of (3-125I-iodobenzoyl)norbiotinamide-labeled exosomes in the liver was decreased by the preinjection of PS-containing liposomes. These results indicate that the negative charge of PS in exosomal membranes is involved in the recognition and clearance of intravenously injected exosomes by macrophages.

Effect of Spacers on the Bipolar Electrostatic Charge Properties of Metered Dose Inhaler Aerosols-A Case Study With Tilade®.

Aerosols emitted from metered dose inhalers (MDIs) are generally electrically charged and bipolar in nature. Although a spacer can effectively dampen the charge magnitude of aerosols, the electrostatic interactions between the positively and negatively charged particles and the spacer have not yet been characterized separately. The Bipolar Charge Analyzer (BOLAR) was employed to investigate interactions between the spacer and the charged aerosols. Three individual actuations of Tilade® MDI were introduced without a spacer and through an antistatic AeroChamber Plus® Z Stat®, an uncoated and a detergent-coated AeroChamber Plus® spacer into the BOLAR at 60 L/min. Charge and mass profiles were determined. The surface potential of spacers followed the order of uncoated > detergent-coated > antistatic spacer. The spacers had minimal impact on the positively charged particles but the charge magnitude of the negatively charged particles was in the opposite order as the spacer surface potential. The charge-to-mass ratio of particles had little alteration for all measurements. Negatively charged particles had a higher tendency to deposit on the spacer walls, possibly due to their higher abundance in the confined spacer volume. The bipolar data may prove useful for designing better MDIs and spacers and modelling lung deposition of charged aerosol particles.