An in vivo study with 19 rabbits was completed. Half of the exposed rabbits had a magnetic field placed externally over their right lung. Magnetic resonance images of the lungs were acquired to determine the iron concentrations in the right and left lung of each animal. The right/left ratio increased in the middle and basal regions of the lung. With further optimization, this technique could be an effective method for targeted drug delivery. Additionally, the feasibility of increasing the length of high aspect ratio particles for improved targeted drug delivery was explored. An ultrasonic nozzle was pulsed into a large evaporation chamber. Individual particles were found to be double the original length. However, due to locally increased humidity the droplets were not dried, except with the use of an orifice to rapidly accelerate and break apart the larger droplets. The complications associated with this method make it an undesirable and unfeasible method of creating longer particles.

No description available.

The dynamics of particle laden flows are integral to the analysis of toxic particle deposition and medical respiratory aerosol delivery. Computational fluid-particle dynamics (CFPD) can play a critical role in developing a better understanding of particle laden flows, especially in a number of under-explored areas. The applications considered in this study include both the numerical aspects and the physical phenomena of respiratory aerosol transport. Objective I: Considering the effects of mesh type and grid convergence, four commonly implemented mesh styles were applied to a double bifurcation respiratory geometry and tested for flow patterns and aerosol deposition. Results indicated that the mesh style employed had a significant effect on the transport and deposition of aerosols with hexahedral meshes being most accurate. Objective II: In order to evaluate the effects of bronchoconstriction under exhalation conditions, normal and constricted pediatric airway models were considered. Results include (i) a significant increase in deposition for constricted airways, and (ii) a novel correlation for deposition during exhalation based on the Dean and Stokes numbers. Objective IIIa: Considering evaluation of an aerosol size sampler, an eight-stage Andersen cascade impactor (ACI) was numerically analyzed. The numerical simulations indicated high non-uniformity and recirculation in the flow field. Numerical predictions of retention fraction matched well with existing experiments (0.5 – 11% error). Objective IIIb: As an extension to this study, numerical predictions of electrostatic charge effects on aerosol transport and deposition in the ACI were presented. Charges consistent with standard pharmaceutical pressurized metered dose inhalers and dry powder inhalers were considered. The numerical predictions indicated that charged aerosols deposit as if they were 5 – 85% larger due to electrostatic effects. Applications of the studies considered include (i) quantitative guidance in selecting numerical mesh styles and development of standard grid convergence criteria, (ii) the development of more accurate whole-lung deposition models that better evaluate exhalation conditions,(iii) improvements in the design of pharmaceutical assessment and delivery devices, and (vi) correction values to account for electrostatic charge on pharmaceutical aerosols.

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.