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.
| Identifer | oai:union.ndltd.org:ADTP/216195 |
| Date | January 2007 |
| Creators | Kwok, Philip Chi Lip |
| Publisher | Faculty of Pharmacy |
| Source Sets | Australiasian Digital Theses Program |
| Detected Language | English |
| Rights | The author retains copyright of this thesis., http://www.library.usyd.edu.au/copyright.html |
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