Pressurized metered-dose inhalers (pMDIs) are the most widely-prescribed inhaler devices for therapeutic aerosol delivery in the treatment of lung diseases. In spite of its undoubted therapeutic and commercial success, the propellant flow mechanics and aerosol formation by the pMDIs is poorly understood. The process involves a complex transient cavitating turbulent fluid that flashes into rapidly evaporating droplets, but details remain elusive, partly due to the difficulty of performing experiments at the small length scales and short time scales. The objective of the current work is the development of a numerical model to predict the internal flow conditions (pressure, temperature, velocity, void fraction, quality, etc.) and provide deeper insight into the atomization process and fluid mechanics involved in the twin-orifice of pMDIs. The main focus is propellant metastability, which has been identified by several past authors as a key element that is missing in accounts of pMDI performance. First the flashing propellant flow through single orifice systems (both long and short capillary tubes) was investigated using three different models : homogeneous equilibrium model (HEM), delayed equilibrium model (DEM) and improved delayed equilibrium model (IDEM). Both, the pure propellants and the propellant mixtures were used as working fluid. The numerical results were compared with the experimental data. For long capillary tubes the three models gave reasonable predictions, but the present results showed that DEM predicts the mass flow rate well for pure propellants and IDEM predicts the mass flow rate well for propellant mixtures. For short capillary tubes, the present results showed that DEM predicts the mass flow rate and pressure distribution along the short tube better compared to HEM and IDEM. The geometry of the twin-orifice system of a pMDI is complex and involves several singularities (sudden enlargements and sudden contractions). Various assumptions were made to evaluate their effect on the vaporisation process and to evaluate the flow variables after the shock at the exit of the spray orifice when the flow is choked. Also, three different propellant flow regimes were explored at the inlet of the valve orifice. A specific combination of assumptions, which offers good agreement with the experimental data was selected for further computations. Numerical investigations were carried out using delayed equilibrium model (DEM) with these new assumptions to validate the two-phase metastable flow through twin-orifice systems with continuous flows of various propellants studied previously by Fletcher (1975) and Clark (1991). A new correlation was developed for the coefficient in the relaxation equation. Along with this correlation a constant coefficient was used in the relaxation equation to model the metastability. Both the coefficients showed good agreement against the Fletcher's experimental data. The comparison with the Clark s experimental data showed that the new correlation coefficient predicted the mass flow rate well in compare to that of the constant coefficient, but over predicted the expansion chamber pressure. The DEM with both the coefficients for continuous discharge flows were applied to investigate the quasi-steady flashing flow inside the metered discharge flows at various time instants. The DEM results were compared with the Clark s metered discharge experimental data and the well established homogeneous equilibrium model (HEM). The comparison between the HEM and DEM with Clark s (1991) experimental data showed that the DEM predicted the mass flow well in compare to that of HEM. Moreover, both the models underpredicted the expansion chamber pressure and temperature. The findings of the present thesis have given a better understanding of the role played by the propellant metastability inside the twin-orifice system of pMDIs. Also, these have provided detailed knowledge of thermodynamic state, void fraction and critical velocity of the propellant at the spray orifice exit, which are essential step towards the development of improved atomisation models. Improved understanding of the fluid mechanics of pMDIs will contribute to the development of next-generation pMDI devices with higher treatment efficacy, capable of delivering a wider range of therapeutic agents including novel therapies based around.

[pt] O problema de transferência de calor, que ocorre durante o escoamento laminar de um fluido de Herschel-Bulkley na região de entrada de tubos é estudado. O número de Nusselt é obtido como uma função da coordenada axial, tensão limite de escoamento e índice de comportamento. São examinadas duas condições de contorno térmicas : fluxo de calor uniforme na parede e temperatura uniforme na parede. Esta análise é feita considerando, primeiramente, as propriedades do líquido independentes da temperatura. Em uma fase posterior, investiga-se o efeito da variação da tensão de escoamento e do índice de consistência com a temperatura. É investigada a influência de alguns parâmetros sobre a transferência de calor. Para o caso das propriedades independentes da temperatura, constatou-se a influência do índice de comportamento e do raio de plug flow sobre o perfil de velocidade. Quando o índice de comportamento é menor que 1, ou o raio de plug flow é maior que 0, o perfil de velocidade fica mais achatado. Em função disto, o número de Nusselt aumenta nestes casos. Os números de Reynolds e Peclet não afetam a troca de calor no escoamento totalmente desenvolvido, porém têm um papel significativo na região de entrada do tubo. Os resultados mostram que a hipótese de fluidos com propriedades independentes da temperatura não muda, o comportamento qualitativo do fluido frente à transferência de calor, embora quantitativamente ocorram mudanças significativas. / [en] The heat transfer problem that occurs during the laminar flow of a Herschel-Bulkley fluid through the entrance portion of tubes is studied. The Nusselt number is obtained as a function of the axial coordinate, yield stress and behavior index. Two different thermal boundary conditions are investigated: uniform wall heat flux and uniform wall temperature. The analysis is firstly carried out assuming that the .reological prop- erties do not depend on temperature. Then the effect of temperature on the yield stress and consistency index is considered for a few representative cases. The behavior index less than one or the plug flow radius greather than zero makes the velocity profile flater. As a result higher Nusselt numbers are obtained. The Reynolds and Peclet numbers do not affec t the flow in the fully developed region, however they play a significative hole in the entrance region. The results show that assumption of temperature –independent properties does not change the qualitative heat transfer behavior, although quantitatively there are significant changes.