Discrete Element Method Evaluation of Triboelectric Charging Due to Powder Handling in the Capsule of a DPI.

The generation and accumulation of an electrostatic charge from handling pharmaceutical powders is a well-known phenomenon, given the insulating nature of most APIs (Active Pharmaceutical Ingredients) and excipients. In capsule-based DPIs (Dry Powder Inhalers), the formulation is stored in a gelatine capsule placed in the inhaler just before inhalation. The action of capsule filling, as well as tumbling or vibration effects during the capsule life cycle, implies a consistent amount of particle-particle and particle-wall contacts. A significant contact-induced electrostatic charging can then take place, potentially affecting the inhaler's efficiency. DEM (Discrete Element Method) simulations were performed on a carrier-based DPI formulation (salbutamol-lactose) to evaluate such effects. After performing a comparison with the experimental data on a carrier-only system under similar conditions, a detailed analysis was conducted on two carrier-API configurations with different API loadings per carrier particle. The charge acquired by the two solid phases was tracked in both the initial particle settling and the capsule shaking process. Alternating positive-negative charging was observed. Particle charging was then investigated in relation to the collision statistics, tracking the particle-particle and particle-wall events for the carrier and API. Finally, an analysis of the relative importance of electrostatic, cohesive/adhesive, and inertial forces allowed the importance of each term in determining the trajectory of the powder particles to be estimated.

Heat stress assessment in artistic glass units.

Heat stress in glass industry is mainly studied in large and highly mechanized manufacturing Units. To the contrary, few studies were carried out in small factories specialized in hand-made products. To stress the need of combined objective and medical surveys in these environments, this paper deals with a simultaneous climatic and physiological investigation of working conditions in artistic crystal glass factories in Tuscany (Italy). The microclimatic monitoring, through a continuous survey has been carried out in early spring. The main physiological parameters (metabolic rate, heart rate, tympanic temperature and water loss) were measured over the whole shifts. The results show that, despite the arduousness of the working conditions, the heat stress levels are physiologically tolerable. The predictions made using the PHS model at the Analysis level described in ISO 15265 agree closely to the observed values, validating the use of PHS model in these conditions. This model was then used to analyse what is likely to be the situation during the summer. It is concluded that the heat constraint will be very high and that some steps must be taken from the spring to monitor closely the exposed workers in the summer and take measures to prevent any heat accident.

Evaluation of the metabolic rate based on the recording of the heart rate.

The assessment of harsh working conditions requires a correct evaluation of the metabolic rate. This paper revises the basis described in the ISO 8996 standard for the evaluation of the metabolic rate at a work station from the recording of the heart rate of a worker during a representative period of time. From a review of the literature, formulas different from those given in the standard are proposed to estimate the maximum working capacity, the maximum heart rate, the heart rate and the metabolic rate at rest and the relation (HR vs. M) at the basis of the estimation of the equivalent metabolic rate, as a function of the age, height and weight of the person. A Monte Carlo simulation is used to determine, from the approximations of these parameters and formulas, the imprecision of the estimated equivalent metabolic rate. The results show that the standard deviation of this estimate varies from 10 to 15%.

On the Effect of Thermophysical Properties of Clothing on the Heat Strain Predicted by PHS Model.

Procedures and equations reported in ISO 9920 for the correction of basic thermophysical clothing properties taking into account pumping effect and air movement are very different from those used by the Predicted Heat Strain (PHS) model in ISO 7933. To study the effect of these differences on the assessment of hot environments using the PHS model, an analysis focusing on the modelling of the dynamic thermal insulation and the vapour resistance of the clothing reported in ISO 9920 and ISO 7933 standards will be discussed in this paper. The results are useful evidence to start a discussion on the best practice for dealing with clothing thermophysical properties and underline the need to harmonize the entire set of standards in the field of the Ergonomics of the Thermal Environment. ISO 7933 is presently under revision.

WBGT index revisited after 60 years of use.

The Wet Bulb Globe Temperature (WBGT) seems to be still used world widely for the evaluation of heat stress conditions and it is recommended by ISO and American Conference of Governmental Industrial Hygienists as a screening method. Unfortunately, many occupational health practitioners and users appear to be unaware of its limitations. As the ISO 7243 Standard, based on WBGT, is presently under revision, it is an appropriate time to review the validity and applicability of this empirical approach to evaluate heat stress. This article underlines the main issues about the WBGT index from a rational perspective.

On the transition thermal discomfort to heat stress as a function of the PMV value.

ISO 15265 Standard - Ergonomics of the thermal environment - Risk assessment strategy for the prevention of stress or discomfort in thermal working conditions - can be considered as a key document for helping responsible for the health protection and prevention of working situations. According to the SOBANE strategy, this standard provides a three-step protocol aimed to the prevention, elimination or reduction of risks affecting the workplaces. Although both methods and procedures suggested by ISO 15265 appear very clear, this standard could bring in confusion both beginners and not specialists in occupational health concerning Predicted Mean Vote (PMV) threshold values consistent with comfort - hot discomfort and the discomfort - hot stress transitions. In this work such matter has been extensively discussed showing a certain difficulty in the definition of an unambiguous PMV threshold value for each working situation in any microclimate.

Notes on the implementation of the IREQ model for the assessment of extreme cold environments.

This paper has been devoted to the difficulties that practitioners, skilled ergonomists or occupational health experts could find in the assessment of cold environments by means of (insulation required) IREQ model at the base of the (International Standardization Organization) ISO 11079 Standard. The in-depth analysis discussed here has underlined several difficulties about: (a) the graphical calculation of the predicted limit exposures; (b) some differences in both IREQ and (duration limit exposure) DLE values reported in ISO 11079; and (c) some errors and incongruities in the program available online for the assessment of DLEs. These occurrences lead to the systematic overestimation of the DLE that exceed up to 4 h, those obtained by means of the figures reported in the Standard with the consequent unreliable assessment. Such matters justify the need to promote, in the whole scientific community involved in the ergonomics of the thermal environment, an in-depth discussion on the best practice to be followed for the assessment of extreme cold environments by means of IREQ model. PRACTITIONER SUMMARY: Incongruities in IREQ model and errors in the code suggested by ISO 11079 Standard prevent a reliable assessment of cold environments with DLE systematically overestimated. Therefore IREQ model has been theoretically investigated trying to help both neophytes and skilled ergonomists on the best practice to be followed.

On the problems related to natural wet bulb temperature indirect evaluation for the assessment of hot thermal environments by means of WBGT.

This paper deals with the indirect evaluation of the natural wet bulb temperature, t (nw), one of the two quantities forming the basis of the well-known wet bulb globe temperature (WBGT) index, considered worldwide to be a suitable and user-friendly tool for the preliminary assessment of hot thermal environments. This quantity can be measured by a wet bulb thermometer (a temperature sensor covered with a wetted wick naturally ventilated) or, if this is not available, calculated from other microclimatic parameters (i.e. the air temperature, the globe temperature, the air velocity, and the humidity) using a quite trivial energy balance equation. Because of the strong non-linear structure of such an equation, the risk of a multiplicity of steady state solutions could result in the failure to obtain a reliable index evaluation. To dispel all doubts, this work carries out an in-depth analysis of the heat balance equation to be solved for the indirect evaluation of the natural wet bulb temperature. A preliminary investigation of each heat flow term involved in the heat balance on the sensor has been carried out; in a second phase a special continuation method has been implemented, highlighting the effect of microclimatic parameters on the multiplicity of solutions. Results show that under free convection the evaluation produces a single solution only under uniform conditions, whereas in the presence of even slight differences between the air temperature and the mean radiant temperature, there can be as many as three solutions. This phenomenon, if confirmed by a further experimental investigation, could become a difficult matter since a sensor, in principle, has to read a unique value of the quantity measured. In any case, from a numerical point of view, the presence of many values of tnw greatly reduces the possibility of an indirect WBGT calculation from the other involved physical quantities; as a consequence, the indirect evaluation of WBGT should be clearly avoided based on ISO 7243 Standard.

Thermal environment assessment reliability using temperature--humidity indices.

A reliable assessment of the thermal environment should take into account the whole of the six parameters affecting the thermal sensation (air temperature, air velocity, humidity, mean radiant temperature, metabolic rate and thermo-physical properties of clothing). Anyway, the need of a quick evaluation based on few measurements and calculations has leaded to like best temperature-humidity indices instead of rational methods based on the heat balance on the human body. Among these, Canadian Humidex, preliminarily used only for weather forecasts, is becoming more and more widespread for a generalized assessment of both outdoor and indoor thermal environments. This custom arouses great controversies since using an index validated in outdoor conditions does not assure its indoor reliability. Moreover is it really possible to carry out the thermal environment assessment ignoring some of variables involved in the physiological response of the human body? Aiming to give a clear answer to these questions, this paper deals with a comparison between the assessment carried out according to the rational methods suggested by International Standards in force and the Humidex index. This combined analysis under hot stress situations (indoor and outdoor) has been preliminarily carried out; in a second phase the study deals with the indoor comfort prediction. Obtained results show that Humidex index very often leads to the underestimation of the workplace dangerousness and a poor reliability of comfort prediction when it is used in indoor situations.

Intra- and intermolecular NMR studies on the activation of arylcyclometallated hafnium pyridyl-amido olefin polymerization precatalysts.

Pyridyl-amido catalysts have emerged recently with great promise for olefin polymerization. Insights into the activation chemistry are presented in an initial attempt to understand the polymerization mechanisms of these important catalysts. The activation of C1-symmetric arylcyclometallated hafnium pyridyl-amido precatalysts, denoted Me2Hf{N(-),N,C(-)} (1, aryl = naphthyl; 2, aryl = phenyl), with both Lewis (B(C6F5)3 and [CPh3][B(C6F5)4]) and Brønsted ([HNR3][B(C6F5)4]) acids is investigated. Reactions of 1 with B(C6F5)3 lead to abstraction of a methyl group and formation of a single inner-sphere diastereoisomeric ion pair [MeHf{N(-),N,C(-)}][MeB(C6F5)3] (3). A 1:1 mixture of the two possible outer-sphere diastereoisomeric ion pairs [MeHf{N(-),N,C(-)}][B(C6F5)4] (4) is obtained when [CPh3][B(C6F5)4] is used. [HNR3][B(C6F5)4] selectively protonates the aryl arm of the tridentate ligand in both precatalysts 1 and 2. A remarkably stable [Me2Hf{N(-),N,C2}][B(C6F5)4] (5) outer-sphere ion pair is formed when the naphthyl substituent is present. The stability is attributed to a hafnium/eta(2)-naphthyl interaction and the release of an eclipsing H-H interaction between naphthyl and pyridine moieties, as evidenced through extensive NMR studies, X-ray single crystal investigation and DFT calculations. When the aryl substituent is phenyl, [Me2Hf{N(-),N,C2}][B(C6F5)4] (10) is originally obtained from protonation of 2, but this species rapidly undergoes remetalation, methane evolution, and amine coordination, giving a diastereomeric mixture of [MeHf{N(-),N,C(-)}NR3][B(C6F5)4] (11). This species transforms over time into the trianionic-ligated [Hf{N(-),C(-),N,C(-)}NR3][B(C6F5)4] (12) through activation of a C-H bond of an amido-isopropyl group. In contrast, ion pair 5 does not spontaneously undergo remetalation of the naphthyl moiety; it reacts with NMe2Ph leading to [MeHf{N(-),N}NMe2C6H4][B(C6F5)4] (7) through ortho-metalation of the aniline. Ion pair 7 successively undergoes a complex transformation ultimately leading to [Hf{N(-),C(-),N,C(-)}NMe2Ph][B(C6F5)4] (8), strictly analogous to 12. The reaction of 5 with aliphatic amines leads to the formation of a single diastereomeric ion pair [MeHf{N(-),N,C(-)}NR3][B(C6F5)4] (9). These differences in activation chemistry are manifested in the polymerization characteristics of these different precatalyst/cocatalyst combinations. Relatively long induction times are observed for propene polymerizations with the naphthyl precatalyst 1 activated with [HNMe3Ph][B(C6F5)4]. However, no induction time is present when 1 is activated with Lewis acids. Similarly, precatalyst 2 shows no induction period with either Lewis or Brønsted acids. Correlation of the solution behavior of these ion pairs and the polymerization characteristics of these various species provides a basis for an initial picture of the polymerization mechanism of these important catalyst systems.