Chan, Ka Man Carmen. / "October 2009." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 160-165). / Abstracts in English and Chinese. / Table of Contents --- p.I / Acknowledgements --- p.IV / Abstract --- p.V / Abstract (Chinese version) --- p.VIII / List of Figures --- p.X / List of Tables --- p.XVIII / Chapter Chapter One. --- Introduction / Chapter 1.1 --- Pulmonary drug delivery --- p.1 / Chapter 1.2 --- Inhalation drug delivery systems --- p.4 / Chapter 1.3 --- Dry powder inhalation aerosols --- p.5 / Chapter 1.3.1 --- Principle of operation of DPIs --- p.5 / Chapter 1.3.2 --- Aerodynamic diameter --- p.6 / Chapter 1.3.2.1 --- Fine particle fraction --- p.8 / Chapter 1.3.3 --- Dispersibility --- p.8 / Chapter 1.3.4 --- Factors that affect dispersibility --- p.9 / Chapter 1.3.4.1 --- Particle Size --- p.9 / Chapter 1.3.4.2 --- Particle Density and Morphology --- p.10 / Chapter 1.3.4.3 --- Interparticulate interactions一Cohesion and adhesion --- p.11 / Chapter 1.3.4.3.1 --- Surface energetics --- p.11 / Chapter 1.3.4.3.2 --- Effect of hygroscopicity and electrostatic charges --- p.12 / Chapter 1.4 --- Particle formation techniques for DPI formulation --- p.14 / Chapter 1.4.1 --- Spray-drying --- p.14 / Chapter 1.4.2 --- Surface modification --- p.16 / Chapter 1.5 --- Physical characterization --- p.17 / Chapter 1.5.1 --- Laser diffraction --- p.17 / Chapter 1.5.2 --- X-ray powder diffraction --- p.18 / Chapter 1.5.3 --- Thermal analysis --- p.19 / Chapter 1.5.4 --- Particle morphology and surface area --- p.20 / Chapter 1.5.5 --- In vitro aerosol performance --- p.21 / Chapter 1.6 --- Surface characterization --- p.21 / Chapter 1.6.1 --- X-ray photoelectric spectroscopy (XPS) --- p.21 / Chapter 1.6.2 --- Inverse gas chromatography --- p.22 / Chapter 1.7 --- Atomic force microscopy in pharmaceutical science --- p.23 / Chapter 1.7.1 --- Principle of operation --- p.24 / Chapter 1.7.1.1 --- Tapping mode --- p.27 / Chapter 1.7.1.2 --- Contact mode --- p.27 / Chapter 1.8 --- Scope of thesis --- p.29 / Chapter Chapter Two. --- Materials and Methods / Chapter 2.1 --- Materials --- p.32 / Chapter 2.2 --- Methods --- p.32 / Chapter 2.2.1 --- Optimization of spray-drying parameters --- p.32 / Chapter 2.2.2 --- Preparation of spray-dried salbutamol sulphate powders containing different concentrations of amino acid additive --- p.33 / Chapter 2.2.3 --- Physical characterization of spray-dried powders --- p.34 / Chapter 2.2.3.1 --- Particle size and size distribution --- p.34 / Chapter 2.2.3.2 --- Specific surface area --- p.35 / Chapter 2.2.3.3 --- X-ray powder diffraction --- p.35 / Chapter 2.2.3.4. --- Scanning electron microscopy --- p.36 / Chapter 2.2.3.5. --- Thermal analysis --- p.36 / Chapter 2.2.3.5.1 --- Thermogravimetric analysis (TGA) --- p.36 / Chapter 2.2.3.5.2 --- Differential scanning calorimetry (DSC) --- p.36 / Chapter 2.2.3.6 --- Water vapour sorption isotherm --- p.37 / Chapter 2.2.3.7 --- Density measurements --- p.37 / Chapter 2.2.3.8 --- In vitro particle deposition (MSLI) --- p.38 / Chapter 2.2.4 --- Surface characterization of the spray-dried powders --- p.39 / Chapter 2.2.4.1 --- X-ray photoelectric spectroscopy (XPS) --- p.39 / Chapter 2.2.4.2 --- Surface energy measurement by inverse gas chromatography (IGC) --- p.40 / Chapter 2.2.4.2.1 --- Calculation of standard free energy of adsorption --- p.41 / Chapter 2.2.4.2.2 --- Dispersive component of surface free energy and related thermodynamic parameters --- p.42 / Chapter 2.2.4.2.3 --- Specific interactions and associated acid-base properties --- p.43 / Chapter 2.2.5. --- Atomic Force Microscopy (AFM) --- p.43 / Chapter 2.2.5.1. --- Imaging --- p.43 / Chapter 2.2.5.2. --- Force measurements --- p.44 / Chapter 2.2.5.2.1 --- Adhesion force measurements --- p.44 / Chapter 2.2.5.2.2 --- Force curve data conversions --- p.44 / Chapter Chapter Three. --- "Optimal Spray-drying Conditions, Physical Characterization and Aerosol Performance of Additive-modified Spray-dried Salbutamol Sulphate particles" / Chapter 3.1 --- Optimization of spray-drying conditions --- p.46 / Chapter 3.2 --- Effect of phenylalanine on the spray-dried SS particles --- p.52 / Chapter 3.2.1. --- Phenylalanine as the additive --- p.52 / Chapter 3.2.1.1 --- In vitro aerosol performance --- p.53 / Chapter 3.2.1.2 --- Particle morphology --- p.55 / Chapter 3.2.1.3 --- Crystallinity --- p.62 / Chapter 3.2.1.4 --- Particle size distribution and specific surface area --- p.63 / Chapter 3.2.1.5 --- Density --- p.65 / Chapter 3.2.1.6 --- Thermal analysis --- p.66 / Chapter 3.2.1.7 --- Water vapour isotherm --- p.70 / Chapter 3.3 --- Effect of leucine on the spray-dried SS particles --- p.77 / Chapter 3.3.1. --- L-Leucine as the additive --- p.77 / Chapter 3.3.1.1 --- In vitro aerosol performance --- p.78 / Chapter 3.3.1.2 --- Particle morphology --- p.80 / Chapter 3.3.1.3 --- Crystallinity --- p.86 / Chapter 3.3.1.4 --- Particle size distribution and specific surface area --- p.87 / Chapter 3.3.1.5 --- Density --- p.90 / Chapter 3.3.1.6 --- Thermal analysis --- p.92 / Chapter 3.3.1.7 --- Water vapour isotherm --- p.95 / Chapter Chapter Four. --- Surface Characterization of Additive-modified Spray-dried Salbutamol Sulphate Particles / Chapter 4.1 --- X-ray photoelectric spectroscopy --- p.103 / Chapter 4.1.1 --- Phenylalanine --- p.103 / Chapter 4.1.2 --- Leucine --- p.104 / Chapter 4.2 --- Inverse gas chromatography --- p.105 / Chapter 4.2.1 --- Phenylalanine --- p.105 / Chapter 4.2.2 --- Leucine --- p.107 / Chapter 4.3 --- Atomic force microscopy --- p.109 / Chapter 4.3.1 --- Surface topography --- p.109 / Chapter 4.3.2 --- Adhesive force measurements --- p.118 / Chapter Chapter Five. --- Conclusions and Suggestions for Future Works / Chapter 5.1 --- Conclusions --- p.139 / Chapter 5.1.1 --- Physical properties --- p.139 / Chapter 5.1.2 --- Surface characteristics and aerosol performance --- p.140 / Chapter 5.2 --- Future studies --- p.142 / Appendix --- p.143 / References --- p.160

Chan, Pui. / "November, 2009." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 108-114). / Abstracts in English and Chinese. / Table of Contents --- p.i / Acknowledgement --- p.vi / Abstract --- p.vii / Abstract (Chinese) --- p.ix / Chapter Chapter One --- Introduction / Chapter 1.1. --- Pulmonary Route for Drug Delivery --- p.2 / Chapter 1.2. --- Factors Affecting the Performance of Inhaled Formulations --- p.3 / Chapter 1.2.1. --- Particle Aerodynamic Diameter --- p.4 / Chapter 1.2.2. --- Dispersibility of Particles --- p.5 / Chapter 1.2.3. --- Clearance Mechanism in Lung and Dissolution of Particles --- p.6 / Chapter 1.3. --- Production of Dry Powder Inhalation by Spray Drying --- p.7 / Chapter 1.4. --- Approaches to Enhance Aerosol Performance of Spray Dried Particles --- p.8 / Chapter 1.4.1 --- Porous/Hollow Particles --- p.9 / Chapter 1.4.2 --- Non-Porous Corrugated Particles --- p.10 / Chapter 1.4.3 --- Blends and Ternary Systems --- p.10 / Chapter 1.4.4 --- Surface Energy and Crystallinity Modification --- p.11 / Chapter 1.4.5 --- Other Approaches to Enhancing Aerosol Performance --- p.12 / Chapter 1.5 --- Objectives and Rationale of the Present Study --- p.13 / Chapter 1.6 --- Scope of Present Study and Particle Characterization Techniques Employed --- p.14 / Chapter 1.6.1 --- Microscopy and Particle Density Measurements --- p.14 / Chapter 1.6.2 --- Particle Size Analysis and Particle Dispersibility --- p.15 / Chapter 1.6.3 --- Thermal Analysis and Particle Crystallinity --- p.15 / Chapter 1.6.4 --- Particle Surface Characterization --- p.16 / Chapter 1.6.5 --- Inverse Gas Chromatography --- p.18 / Chapter 1.6.6 --- Fractal Analysis --- p.19 / Chapter 1.6.6.1 --- Background and Origin of Fractal Analysis --- p.19 / Chapter 1.6.6.2 --- Use of Fractal Analysis in Pharmaceutical Research --- p.20 / Chapter 1.6.6.3 --- Methods for fractal analysis --- p.21 / Chapter 1.6.7 --- Atomic Force Microscopy --- p.23 / Chapter 1.6.7.1 --- Background of Atomic Force Microscopy --- p.23 / Chapter 1.6.7.2 --- Characterization of Surface Topography by Atomic Force Microscopy --- p.23 / Chapter 1.6.7.3 --- Measurement of Interaction Forces by Colloid Probe 226}0Ø Microscopy --- p.25 / Chapter 1.6.7.4 --- Use of Atomic Force Microscopy in Pharmaceutical Research --- p.27 / Chapter Chapter Two --- Materials and Methods / Chapter 2.1. --- Materials --- p.30 / Chapter 2.2. --- Equipment --- p.31 / Chapter 2.3. --- Methods --- p.33 / Chapter 2.3.1. --- Powder Preparation --- p.33 / Chapter 2.3.1.1 --- Preparation of Salbutamol Sulphate Samples --- p.33 / Chapter 2.3.1.2 --- Preparation of Disodium Cromoglycate Samples --- p.33 / Chapter 2.3.1.3 --- Preparation of ß-Galactosidase (BG) Samples --- p.34 / Chapter 2.3.2. --- Determination of Aerosol Performance --- p.35 / Chapter 2.3.3. --- Determination of Protein Activity for BG Samples --- p.36 / Chapter 2.3.3.1. --- Enzyme Assay Procedure --- p.37 / Chapter 2.3.3.2. --- Calculation of Enzyme Activity --- p.38 / Chapter 2.3.3.3. --- Determination of Enzyme Activity Retained in Spray-dried Samples --- p.38 / Chapter 2.3.4. --- Physicochemical Characterization of Particles --- p.39 / Chapter 2.3.4.1. --- Scanning Electron Microscopy --- p.39 / Chapter 2.3.4.2. --- Particle Density Determination --- p.39 / Chapter 2.3.4.3. --- Particle Size Analysis --- p.40 / Chapter 2.3.4.4. --- Thermal analysis --- p.41 / Chapter 2.3.4.5. --- Powder X-ray Diffraction --- p.42 / Chapter 2.3.4.6. --- Surface Area Determination --- p.42 / Chapter 2.3.4.7. --- Surface Composition Characterization --- p.43 / Chapter 2.3.4.8. --- Surface Tension Measurement --- p.44 / Chapter 2.3.4.9. --- Inverse Gas Chromatography --- p.45 / Chapter 2.3.4.9.1. --- Calculation of Standard Free Energy of Adsorption --- p.46 / Chapter 2.3.4.9.2. --- Calculation of Dispersive Component of Surface Free Energy --- p.47 / Chapter 2.3.4.9.3. --- Determination of Specific Interactions and Associated Acid-Base Properties --- p.48 / Chapter 2.3.4.10. --- Fractal Analysis --- p.49 / Chapter 2.3.4.11. --- Atomic Force Microscopy --- p.49 / Chapter Chapter Three --- Results / Chapter 3.1. --- In vitro Aerosol Performance --- p.52 / Chapter 3.2. --- Enzyme Activity Retained in BG Samples --- p.55 / Chapter 3.3. --- Scanning Electron Microscopy (SEM) --- p.56 / Chapter 3.3.1. --- SEM of Salbutamol Sulphate Formulations --- p.56 / Chapter 3.3.2. --- SEM of DSCG Formulations --- p.59 / Chapter 3.3.3. --- SEM of BG Formulations --- p.61 / Chapter 3.4. --- Density Measurements --- p.65 / Chapter 3.4.1. --- Densities of Salbutamol Sulphate Formulations --- p.65 / Chapter 3.4.2. --- Densities of DSCG Formulations --- p.66 / Chapter 3.4.3. --- Densities of BG Formulations --- p.67 / Chapter 3.5. --- Particle Size Analysis by Laser Diffraction --- p.68 / Chapter 3.5.1. --- Volume Mean Diameter Measurements --- p.68 / Chapter 3.5.2. --- Particle Size Distributions and Dispersion Patterns of Formulations --- p.70 / Chapter 3.6. --- Thermal Analysis --- p.75 / Chapter 3.7. --- Powder X-ray Diffraction --- p.80 / Chapter 3.8. --- Surface Area Measurements --- p.84 / Chapter 3.9. --- Surface Composition Characterization --- p.85 / Chapter 3.9.1. --- Surface Composition of Salbutamol Sulphate Formulations --- p.85 / Chapter 3.9.2. --- Surface Composition of DSCG Formulations --- p.88 / Chapter 3.9.3. --- Surface Composition of BG/BSA Formulations --- p.89 / Chapter 3.10. --- Surface Tension Measurements --- p.91 / Chapter 3.11. --- Inverse Gas Chromatography --- p.92 / Chapter 3.12. --- Fractal Analysis --- p.93 / Chapter 3.13. --- Atomic Force Microscopy --- p.94 / Chapter Chapter Four --- Discussion / Chapter 4.1. --- Influence of BSA on Aerosol Performance and Protein Integrity --- p.98 / Chapter 4.2. --- Influence of BSA on Physicochemical Properties of Particles --- p.98 / Chapter 4.2.1. --- Influence of BSA on surface corrugation --- p.98 / Chapter 4.2.2. --- Influence of BSA on particle size and dispersion behavior --- p.99 / Chapter 4.2.3. --- Influence of BSA on crystallinity and thermal properties of particles --- p.100 / Chapter 4.2.4. --- Influence of BSA on surface energetics of particles --- p.100 / Chapter 4.3. --- Relationship between Surface Corrugation and Aerosol Performance --- p.101 / Chapter 4.4. --- Mechanism of Surface Modification for BSA on Spray-dried Particles --- p.103 / Chapter Chapter Five --- Conclusions and Future Work / Chapter 5.1. --- Conclusions --- p.106 / Chapter 5.1.1. --- General Aerosolization-Enhancing Effect of BSA --- p.106 / Chapter 5.1.2. --- Surface Modifying Effect of BSA --- p.106 / Chapter 5.1.3. --- Relationship between Surface Corrugation and Aerosol Performance --- p.106 / Chapter 5.2. --- Future Work --- p.107 / References --- p.108