The Mechanics of Inhaled Pharmaceutical Aerosols: An Introduction
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Table of contents
- Contentsv
- Prefaceix
- Acknowledgmentsxi
- Chapter 1. Introduction1
- Chapter 2. Particle Size Distributions3
- 2.1 Frequency and count distributions3
- 2.2 Mass and volume distributions5
- 2.3 Cumulative mass and volume distributions7
- 2.4 Other distribution functions9
- 2.5 Summary of mean and median aerosol particle sizes10
- Chapter 3. Motion of a Single Aerosol Particle in a Fluid17
- 3.1 Drag force18
- 3.2 Settling velocity19
- 3.3 Drag force on very small particles22
- 3.4 Brownian diffusion23
- 3.5 Motion of particles relative to the fluid due to particle inertia25
- 3.6 Similarity of particle motion: the concept of aerodynamic diameter32
- 3.7 Effect of induced electrical charge35
- 3.8 Space charge40
- 3.9 Effect of high humidity on electrostatic charge43
- Chapter 4. Particle Size Changes due to Evaporation or Condensation47
- 4.1 Introduction47
- 4.2 Water vapor concentration at an air–water interface47
- 4.3 Effect of dissolved molecules on water vapor concentration at an air–water interface49
- 4.4 Assumptions needed to develop simplified hygroscopic theory52
- 4.5 Simplified theory of hygroscopic size changes for a single droplet: mass transfer rate57
- 4.6 Simplified theory of hygroscopic size changes for a single droplet: heat transfer rate60
- 4.7 Simplified theory of droplet growth or evaporation of a single droplet whose temperature is cons62
- 4.8 Use of the constant temperature equation for variable temperature conditions and a single drople63
- 4.9 Modifications to simplified theory for multiple droplets: two-way coupled effects67
- 4.10 When are hygrosopic size changes negligible?68
- 4.11 Effect of aerodynamic pressure and temperature changes on hygroscopic effects71
- 4.12 Corrections to simplified theory for small droplets72
- 4.13 Corrections to account for Stefan flow79
- 4.14 Exact solution for Stefan flow82
- 4.15 When can Stefan flow be neglected?85
- Chapter 5. Introduction to the Respiratory Tract93
- 5.1 Basic aspects of respiratory tract geometry93
- 5.2 Breath volumes and flow rates98
- Chapter 6. Fluid Dynamics in the Respiratory Tract105
- 6.1 Incompressibility105
- 6.2 Nondimensional analysis of the fluid equations106
- 6.3 Secondary flow patterns111
- 6.4 Reduction of turbulence by particle motion114
- 6.5 Temperature and humidity in the respiratory tract115
- 6.6 Interaction of air and mucus fluid motion116
- Chapter 7. Particle Deposition in the Respiratory Tract119
- 7.1 Sedimentation of particles in inclined circular tubes119
- 7.2 Sedimentation in alveolated ducts131
- 7.3 Deposition by impaction in the lung133
- 7.4 Deposition in cylindrical tubes due to Brownian diffusion138
- 7.5 Simultaneous sedimentation, impaction and diffusion143
- 7.6 Deposition in the mouth and throat148
- 7.7 Deposition models149
- 7.8 Understanding the effect of parameter variations on deposition154
- 7.9 Respiratory tract deposition156
- 7.10 Targeting deposition at different regions of the respiratory tract164
- 7.11 Deposition in diseased lungs166
- 7.12 Effect of age on deposition167
- 7.13 Conclusion169
- Chapter 8. Jet Nebulizers175
- 8.1 Basic nebulizer operation175
- 8.2 The governing parameters for primary droplet formation178
- 8.3 Linear stability of air flowing across water181
- 8.4 Droplet sizes estimated from linear stability analysis185
- 8.5 Primary droplet formation186
- 8.6 Primary droplet breakup due to abrupt aerodynamic loading187
- 8.7 Primary droplet breakup due to gradual aerodynamic loading191
- 8.8 Empirical correlations195
- 8.9 Droplet production by impaction on baffles202
- 8.10 Degradation of drug due to impaction on baffles209
- 8.11 Aerodynamic size selection of baffles209
- 8.12 Cooling and concentration of nebulizer solutions212
- 8.13 Nebulizer efficiency and output rate216
- 8.14 Charge on droplets produced by jet nebulization216
- 8.15 Summary218
- Chapter 9. Dry Powder Inhalers221
- 9.1 8asic aspects of dry powder inhalers221
- 9.2 The origin of adhesion: van der Waals forces222
- 9.3 van der Waals forces between actual pharmaceutical particles227
- 9.4 Surface energy: a macroscopic view of adhesion230
- 9.5 Effect of water capillary condensation on adhesion234
- 9.6 Electrostatic forces239
- 9.7 Powder entrainment by shear fluidization243
- 9.8 Turbulent deaggregation of agglomerates258
- 9.9 Particle detachment by mechanical acceleration: impaction and vibration269
- 9.10 Concluding remarks273
- Chapter 10. Metered Dose Propellant Inhalers277
- 10.1 Propellant cavitation278
- 10.2 Fluid dynamics in the expansion chamber and nozzle283
- 10.3 Post-nozzle droplet breakup due to gradual aerodynamic loading288
- 10.4 Post-nozzle droplet evaporation290
- 10.5 Add-on devices291
- 10.6 Concluding remarks292
- Index295
The Mechanics of Inhaled Pharmaceutical Aerosols, An Introduction provides a unique and comprehensive treatment of the mechanics of inhaled pharmaceutical aerosols. The book covers a wide range of topics and many new perspectives are given by drawing on research from a variety of fields. Novel, in-depth expositions of the most common delivery devices are given, including nebulizers, dry powder inhalers and propellant metered dose inhalers. The behaviour of aerosols in the respiratory tract is explained in detail, with complete coverage of the fundamentals of current deposition models.
The book begins by providing a comprehensive introduction to aspects of aerosol mechanics that are relevant to inhaled pharmaceutical aerosols. It then gives an exhaustive pedagogical description of the behaviour of evaporating and condensing droplets (both aqueous and propellant-based), an introductory chapter on lung geometry and inhalation patterns, and coverage of relevant aspects of fluid mechanics in the lung. Finally, the book provides invaluable, detailed coverage on the mechanics of common pharmaceutical aerosol delivery systems and deposition in the respiratory tract. Throughout the book are many detailed numerical examples that apply the salient concepts to typical inhaled pharmaceutical aerosols.
This book will be of interest to scientists and engineers involved in the research and development of inhaled pharmaceutical aerosol products. Experienced practitioners will find many new perspectives that will greatly enhance their understanding of this complex and rapidly growing field. For those delivering therapeutic agents to the lung, this book is a must-have. Students and academics will find this book an invaluable tool and for newcomers it is a worthy guide to the diverse fields that must be understood to work in the area of inhaled pharmaceutical aerosols.
The book begins by providing a comprehensive introduction to aspects of aerosol mechanics that are relevant to inhaled pharmaceutical aerosols. It then gives an exhaustive pedagogical description of the behaviour of evaporating and condensing droplets (both aqueous and propellant-based), an introductory chapter on lung geometry and inhalation patterns, and coverage of relevant aspects of fluid mechanics in the lung. Finally, the book provides invaluable, detailed coverage on the mechanics of common pharmaceutical aerosol delivery systems and deposition in the respiratory tract. Throughout the book are many detailed numerical examples that apply the salient concepts to typical inhaled pharmaceutical aerosols.
This book will be of interest to scientists and engineers involved in the research and development of inhaled pharmaceutical aerosol products. Experienced practitioners will find many new perspectives that will greatly enhance their understanding of this complex and rapidly growing field. For those delivering therapeutic agents to the lung, this book is a must-have. Students and academics will find this book an invaluable tool and for newcomers it is a worthy guide to the diverse fields that must be understood to work in the area of inhaled pharmaceutical aerosols.