The assessment of drug formulations delivered by the pressurised metered dose inhaler and used in the treatment of Asthma are assessed commercially using cascade impactors which are the preferred instruments for the assessment of particle size and respirable mass or fraction delivered by inhalation devices. The fundamental principle underpinning the design of cascade impactors is particle motion defined by Stokes theory. The analysis of impactor data raises a number of functional issues as calibration curves have long tails, which are not easily explained by a simplistic application of Stokes law. The atomisation process, propellant flashing, evaporation and aerodynamic properties of the residual drug particle detennine the distribution of the drug particles within the lung and resultant therapeutic effect. The research uses mathematical modelling and computational fluid dynamics (CFD) to evaluate the flow and inertial deposition in the USP throat and the plates of the ACI which is the most widely used cascade impactor. The CFD analysis shows the flow in the outlet section of the USP throat to be unstable for the basic design, when coupled to an outlet extension and when coupled to the ACI via the standard coupler and first jet stage. The modelling also provides insight as to why the calibration curves of the ACI have long tails and reveals a number of issues with the design of the ACI coupler and the fundamental design of impactor jet arrays as well as the position and functional response of upper impactor plates. Additional particle sizing methodologies were used to assess the lognonnal characteristics of the atomised droplets and residual drug particles. The experimental data was compared to current atomisation model and modification recommended and a proposed alternative model with improved fit to the data.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:540809 |
| Date | January 2008 |
| Creators | Davis, A. J. |
| Publisher | Loughborough University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://dspace.lboro.ac.uk/2134/12222 |
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