PhD / Electrostatics of aerosols for inhalation is a relatively new research area. Charge properties of these particles are largely unknown but electrostatic forces have been proposed to potentially influence lung deposition. Investigation on the relationship between formulation and aerosol charging is required to understand the fundamental mechanisms. A modified electrical low pressure impactor was employed to measure the particles generated from metered dose inhalers and dry powder inhalers. This equipment provides detailed size and charge information of the aerosols. The particles were sized by impaction onto thirteen stages. The net charges in twelve of the size fractions were detected and recorded by sensitive electrometers. The drug deposits were quantified by chemical assay. The aerosol charge profiles of commercial metered dose inhalers were product-dependent, which was due to differences in the drug, formulation, and valve stem material. The calculated number of elementary charges per drug particle of size ≤ 6.06 μm ranged from zero to several ten thousands. The high charge levels on particles may have a potential effect on the deposition of the aerosol particles in the lung when inhaled. New plastic spacers marketed for use with metered dose inhalers were found to possess high surface charges on the internal walls, which was successfully removed by detergent-coating. Detergent-coated spacer had higher drug output than the new ones due to the reduced electrostatic particle deposition inside the spacer. Particles delivered from spacers carried lower inherent charges than those directly from metered dose inhalers. Those with higher charges might be susceptible to electrostatic forces inside the spacers and were thus retained. The electrostatic low pressure impactor was further modified to disperse two commercial Tubuhaler® products at 60 L/min. The DPIs showed drug-specific responses to particle charging at different RHs. The difference in hygroscopicity of the drugs may play a major role. A dual mechanistic charging model was proposed to explain the charging behaviours. The charge levels on drug particles delivered from these inhalers were sufficiently high to potentially affect deposition in the airways when inhaled. Drug-free metered dose inhalers containing HFA-134a and 227 produced highly variable charge profiles but on average the puffs were negatively charged, which was thought to be due to the electronegative fluorine atoms in the HFA molecules. The charges of both HFAs shifted towards neutrality or positive polarity with increasing water content. The spiked water might have increased the electrical conductivity and/or decreased the electronegativity of the bulk propellant solution. The number of elementary charges per droplet decreased with decreasing droplet size. This trend was probably due to the redistribution of charges amongst small droplets following electrostatic fission of a bigger droplet when the Raleigh limit was reached.

PhD / Electrostatics of aerosols for inhalation is a relatively new research area. Charge properties of these particles are largely unknown but electrostatic forces have been proposed to potentially influence lung deposition. Investigation on the relationship between formulation and aerosol charging is required to understand the fundamental mechanisms. A modified electrical low pressure impactor was employed to measure the particles generated from metered dose inhalers and dry powder inhalers. This equipment provides detailed size and charge information of the aerosols. The particles were sized by impaction onto thirteen stages. The net charges in twelve of the size fractions were detected and recorded by sensitive electrometers. The drug deposits were quantified by chemical assay. The aerosol charge profiles of commercial metered dose inhalers were product-dependent, which was due to differences in the drug, formulation, and valve stem material. The calculated number of elementary charges per drug particle of size ≤ 6.06 μm ranged from zero to several ten thousands. The high charge levels on particles may have a potential effect on the deposition of the aerosol particles in the lung when inhaled. New plastic spacers marketed for use with metered dose inhalers were found to possess high surface charges on the internal walls, which was successfully removed by detergent-coating. Detergent-coated spacer had higher drug output than the new ones due to the reduced electrostatic particle deposition inside the spacer. Particles delivered from spacers carried lower inherent charges than those directly from metered dose inhalers. Those with higher charges might be susceptible to electrostatic forces inside the spacers and were thus retained. The electrostatic low pressure impactor was further modified to disperse two commercial Tubuhaler® products at 60 L/min. The DPIs showed drug-specific responses to particle charging at different RHs. The difference in hygroscopicity of the drugs may play a major role. A dual mechanistic charging model was proposed to explain the charging behaviours. The charge levels on drug particles delivered from these inhalers were sufficiently high to potentially affect deposition in the airways when inhaled. Drug-free metered dose inhalers containing HFA-134a and 227 produced highly variable charge profiles but on average the puffs were negatively charged, which was thought to be due to the electronegative fluorine atoms in the HFA molecules. The charges of both HFAs shifted towards neutrality or positive polarity with increasing water content. The spiked water might have increased the electrical conductivity and/or decreased the electronegativity of the bulk propellant solution. The number of elementary charges per droplet decreased with decreasing droplet size. This trend was probably due to the redistribution of charges amongst small droplets following electrostatic fission of a bigger droplet when the Raleigh limit was reached.

Aerosol electrostatics is an important property of pharmaceutical aerosols. The electrostatic properties of pMDI aerosols have been shown to be a function of both formulation and packaging components. The modified ELPI enables measurement of aerosol charge as a function of particle size, and the simultaneous determination of the mass distribution using chemical analysis. However, in order to fully assess the cause and effects of aerosol electrostatics in terms of its biological and regulatory implications, it is necessary to understand the basic charging mechanisms inside the pMDI formulation. Electrical resistivity and zeta potential measurements confirmed the presence of charged species within HFA based solutions and suspensions although the nature of these species remains unknown. These measurements were influenced by the cosolvent concentration and to a lesser extent by the presence of soluble drug and surfactant. The mean electrical resistivity of a 7% ethanol / 93% HFA 134a blend (0.83 ± 0.02 MΩ.cm) was significantly lower than that reported for HFA 134a (180 MΩ.cm). Albuterol sulfate demonstrated a positive zeta potential (75.9 ± 26.2 mV) in HFA 134a. Pilot molecular modeling studies, in conjunction with the analysis of particle interactions using HINT, provided an improved understanding of the possible interactions within albuterol sulfate HFA suspension pMDIs. The predominantly negative (-7597 ± 2063) HINT score signified unfavorable interactions between albuterol sulfate and HFA 134a molecules. Systematic investigations of the electrical properties of HFA solution and suspension pMDIs using the modified ELPI demonstrated that the electrical properties were a function of the formulation type (solution/suspension), formulation components and particle size. Experimental BDP solution pMDIs produced predominantly electropositive aerosols (net charge: 160 ± 30 pC) while albuterol sulfate pMDIs produced bipolar charged aerosol clouds (net charge: -162 ± 277 pC). Finally, the modified ELPI was recalibrated using commercially available polydisperse pMDIs as calibration aerosols with a reference Andersen cascade impactor. The mean cut-off diameters for stages 4-12 obtained following recalibration of the modified ELPI were 0.44, 0.56, 0.70, 1.01, 1.40, 2.12, 3.03, 4.75, 6.37 μm, respectively in comparison to those reported by the manufacturer (0.16, 0.27, 0.39, 0.62, 0.96, 1.62, 2.42, 4.05, 6.67 μm, respectively).

Pour évaluer l'impact d’un rejet accidentel ou chronique de polluants dans les écosystèmes, il est important d’étudier le dépôt sec des aérosols en milieu rural. Le manque de données expérimentales en milieu rural sur la vitesse de dépôt sec des particules ayant une taille inférieure à 1 μm conduit à des incertitudes au vu des modèles et de leurs différences, qui vont jusqu’à dépasser un ordre de grandeur. Le but de cette étude est de développer une mesure directe de la vitesse de dépôt sec des aérosols (Vd), notamment en utilisant un impacteur à basse pression (Electrical Low Pressure Impactor, ELPI, DEKATI), à travers des mesures expérimentales in situ. L’originalité de la méthode est le calcul des flux de dépôt par corrélation turbulente. Les vitesses de dépôt sec ont été obtenues pour des aérosols atmosphériques de tailles comprises entre 7 nm et 2 μm, sur un terrain plat dans le sud-ouest de la France, sous différentes conditions atmosphériques, ainsi que sur différents couverts (maïs, herbe, sol nu). Vd est analysée en fonction du diamètre des particules et l’impact des conditions micro météorologiques est étudié. / To evaluate the impact of accidental or chronic pollutant releases on ecosystems, we must study the dry deposition of aerosols in rural areas. The lack of experimental data on the dry deposition velocity of particle sizes below 1 μm over rural environments leads to uncertainties regarding models and differences between them, which exceed one order of magnitude. The aim of thisstudy is to develop a method, especially using an Electrical Low Pressure Impactor (Outdoor ELPI, DEKATI) to determine aerosol dry deposition velocities (Vd) over rural areas through experimental measurements. This method is based on eddy covariance flux calculation and spectral analysis correction. Dry deposition velocities were obtained for atmospheric aerosols sizing from 7 nm to2 μm, in the South-West of France on a flat terrain under varied meteorological conditions andvaried substrates (maize, grass and earth). Vd was analysed as a function of the particle diameters, and the impact of micrometeorological parameters was studied.