Mechanics of Inhaled Pharmaceutical Aerosols (eBook)

Cover 1
Contents 6
Preface 10
Acknowledgments 12
Chapter 1. Introduction 16
Chapter 2. Particle Size Distributions 18
2.1 Frequency and count distributions 18
2.2 Mass and volume distributions 20
2.3 Cumulative mass and volume distributions 22
2.4 Other distribution functions 24
2.5 Summary of mean and median aerosol particle sizes 25
Chapter 3. Motion of a Single Aerosol Particle in a Fluid 32
3.1 Drag force 33
3.2 Settling velocity 34
3.3 Drag force on very small particles 37
3.4 Brownian diffusion 38
3.5 Motion of particles relative to the fluid due to particle inertia 40
3.6 Similarity of particle motion: the concept of aerodynamic diameter 47
3.7 Effect of induced electrical charge 50
3.8 Space charge 55
3.9 Effect of high humidity on electrostatic charge 58
Chapter 4. Particle Size Changes due to Evaporation or Condensation 62
4.1 Introduction 62
4.2 Water vapor concentration at an air–water interface 62
4.3 Effect of dissolved molecules on water vapor concentration at an air–water interface 64
4.4 Assumptions needed to develop simplified hygroscopic theory 67
4.5 Simplified theory of hygroscopic size changes for a single droplet: mass transfer rate 72
4.6 Simplified theory of hygroscopic size changes for a single droplet: heat transfer rate 75
4.7 Simplified theory of droplet growth or evaporation of a single droplet whose temperature is constant 77
4.8 Use of the constant temperature equation for variable temperature conditions and a single droplet 78
4.9 Modifications to simplified theory for multiple droplets: two-way coupled effects 82
4.10 When are hygrosopic size changes negligible? 83
4.11 Effect of aerodynamic pressure and temperature changes on hygroscopic effects 86
4.12 Corrections to simplified theory for small droplets 87
4.13 Corrections to account for Stefan flow 94
4.14 Exact solution for Stefan flow 97
4.15 When can Stefan flow be neglected? 100
Chapter 5. Introduction to the Respiratory Tract 108
5.1 Basic aspects of respiratory tract geometry 108
5.2 Breath volumes and flow rates 113
Chapter 6. Fluid Dynamics in the Respiratory Tract 120
6.1 Incompressibility 120
6.2 Nondimensional analysis of the fluid equations 121
6.3 Secondary flow patterns 126
6.4 Reduction of turbulence by particle motion 129
6.5 Temperature and humidity in the respiratory tract 130
6.6 Interaction of air and mucus fluid motion 131
Chapter 7. Particle Deposition in the Respiratory Tract 134
7.1 Sedimentation of particles in inclined circular tubes 134
7.2 Sedimentation in alveolated ducts 146
7.3 Deposition by impaction in the lung 148
7.4 Deposition in cylindrical tubes due to Brownian diffusion 153
7.5 Simultaneous sedimentation, impaction and diffusion 158
7.6 Deposition in the mouth and throat 163
7.7 Deposition models 164
7.8 Understanding the effect of parameter variations on deposition 169
7.9 Respiratory tract deposition 171
7.10 Targeting deposition at different regions of the respiratory tract 179
7.11 Deposition in diseased lungs 181
7.12 Effect of age on deposition 182
7.13 Conclusion 184
Chapter 8. Jet Nebulizers 190
8.1 Basic nebulizer operation 190
8.2 The governing parameters for primary droplet formation 193
8.3 Linear stability of air flowing across water 196
8.4 Droplet sizes estimated from linear stability analysis 200
8.5 Primary droplet formation 201
8.6 Primary droplet breakup due to abrupt aerodynamic loading 202
8.7 Primary droplet breakup due to gradual aerodynamic loading 206
8.8 Empirical correlations 210
8.9 Droplet production by impaction on baffles 217
8.10 Degradation of drug due to impaction on baffles 224
8.11 Aerodynamic size selection of baffles 224
8.12 Cooling and concentration of nebulizer solutions 227
8.13 Nebulizer efficiency and output rate 231
8.14 Charge on droplets produced by jet nebulization 231
8.15 Summary 233
Chapter 9. Dry Powder Inhalers 236
9.1 8asic aspects of dry powder inhalers 236
9.2 The origin of adhesion: van der Waals forces 237
9.3 van der Waals forces between actual pharmaceutical particles 242
9.4 Surface energy: a macroscopic view of adhesion 245
9.5 Effect of water capillary condensation on adhesion 249
9.6 Electrostatic forces 254
9.7 Powder entrainment by shear fluidization 258
9.8 Turbulent deaggregation of agglomerates 273
9.9 Particle detachment by mechanical acceleration: impaction and vibration 284
9.10 Concluding remarks 288
Chapter 10. Metered Dose Propellant Inhalers 292
10.1 Propellant cavitation 293
10.2 Fluid dynamics in the expansion chamber and nozzle 298
10.3 Post-nozzle droplet breakup due to gradual aerodynamic loading 303
10.4 Post-nozzle droplet evaporation 305
10.5 Add-on devices 306
10.6 Concluding remarks 307
Index 310