Pulmonary Drug Delivery

Advances and Challenges
Herausgegeben von Nokhodchi, Ali; Martin, Gary P.

• Gebundenes Buch

Produktbeschreibung

Drug therapy via inhalation route is at the cutting edge of modern drug delivery research. There has been significant progress on the understanding of drug therapy via inhalation products. However, there are still problems associated with their formulation design, including the interaction between the active pharmaceutical ingredient(s) (APIs), excipients and devices. This book seeks to cover some of the most pertinent issues and challenges of such formulation design associated with industrial production and desirable clinical outcome.

The chapter topics have been selected with a view to integrating the factors that require consideration in the selection and design of device and formulation components which impact upon patient usability and clinical effectiveness. The challenges involved with the delivery of macromolecules by inhalation to both adult and pediatric patients are also covered.

Written by leading international experts from both academia and industry, the book will help readers (formulation design scientists, researchers and post-graduate and specialized undergraduate students) develop a deep understanding of key aspects of inhalation formulations as well as detail ongoing challenges and advances associated with their development.

Produktdetails

• Advances in Pharmaceutical Technology .1
• Verlag: Wiley & Sons
• 1. Auflage
• Seitenzahl: 384
• Erscheinungstermin: 3. August 2015
• Englisch
• Abmessung: 246mm x 173mm x 20mm
• Gewicht: 590g
• ISBN-13: 9781118799543
• ISBN-10: 1118799542
• Artikelnr.: 42297361

Autorenporträt

ALI NOKHODCHI School of Life Sciences, University of Sussex, UK GARY P. MARTIN Institute of Pharmaceutical Science, King's College London, UK

Inhaltsangabe

List of Contributors xiii Series Preface xvii Preface xix 1. Lung Anatomy
and Physiology and Their Implications for Pulmonary Drug Delivery 1 Rahul
K. Verma, Mariam Ibrahim, and Lucila Garcia-Contreras 1.1 Introduction 2
1.2 Anatomy and Physiology of Lungs 2 1.2.1 Macro- and Microstructure of
the Airways and Alveoli as It Pertains to Drug Delivery 2 1.2.2 Lung
Surfactant 4 1.2.3 Pulmonary Blood Circulation 5 1.3 Mechanisms of Aerosol
Deposition 5 1.3.1 Impaction 6 1.3.2 Sedimentation 6 1.3.3 Interception 6
1.3.4 Diffusion 7 1.4 Drug Absorption 7 1.4.1 Mechanisms of Drug Absorption
from the Lungs 7 1.5 Physiological Factors Affecting the Therapeutic
Effectiveness of Drugs Delivered by the Pulmonary Route 8 1.5.1 Airway
Geometry 8 1.5.2 Inhalation Mode 8 1.5.3 Airflow Rate 9 1.5.4 Mechanism of
Particle Clearance 9 1.5.5 Lung Receptors 10 1.5.6 Disease States 11 1.5.7
Effect of Age and Gender Difference 11 1.6 Computer Simulations to Describe
Aerosol Deposition in Health and Disease 11 1.6.1 Semiempirical Models 12
1.6.2 Deterministic Models 12 1.6.3 Trumpet Models (One-Dimensional) 12
1.6.4 Stochastic, Asymmetric Generation Models 13 1.6.5 Computation Fluid
Dynamics (CFD)-Based Model 13 1.7 Conclusions 13 References 14 2. The Role
of Functional Lung Imaging in the Improvement of Pulmonary Drug Delivery 19
Andreas Fouras and Stephen Dubsky 2.1 Introduction 19 2.1.1 Particle
Deposition 20 2.1.2 Regional Action of Delivered Drug 22 2.1.3 The Role of
Functional Lung Imaging in Pulmonary Drug Delivery 22 2.2 Established
Functional Lung Imaging Technologies 23 2.2.1 Computed Tomography 23 2.2.2
Ventilation Measurement using 4DCT Registration-based Methods 24 2.2.3
Hyperpolarized Magnetic Resonance Imaging 24 2.2.4 Electrical Impedance
Tomography 25 2.2.5 Nuclear Medical Imaging (PET/SPECT) 25 2.3 Emerging
Technologies 26 2.3.1 Phase-contrast Imaging 26 2.3.2 Grating
Interferometry 27 2.3.3 Propagation-based Phase-contrast Imaging 28 2.3.4
Functional Lung Imaging using Phase Contrast 28 2.3.5 Laboratory
Propagation-based Phase-contrast Imaging 29 2.4 Conclusion 30 References 31
3. Dry Powder Inhalation for Pulmonary Delivery: Recent Advances and
Continuing Challenges 35 Simone R. Carvalho, Alan B. Watts, Jay I. Peters,
and Robert O. Williams III 3.1 Introduction 36 3.2 Dry Powder Inhaler
Devices 37 3.2.1 Overview 37 3.2.2 Recent Innovations in Dry Powder Inhaler
Technology 39 3.3 New Developments in DPI Formulations and Delivery 43
3.3.1 Particle Surface Modification 43 3.3.2 Particle Engineering
Technology for Pulmonary Delivery 44 3.4 Characterization Methods of Dry
Powder Inhaler Formulations 50 3.5 Conclusion 52 References 53 4. Pulmonary
Drug Delivery to the Pediatric Population - A State-of-the-Art Review 63
Marie-Pierre Flament 4.1 Introduction 63 4.2 Patient Consideration 64 4.2.1
Anatomy and Physiology of Children's Lungs 64 4.2.2 Nasal Versus Oral
Inhalation 65 4.2.3 Patient-related Factors Influencing Aerosol Deposition
66 4.2.4 Age and Dosage Forms of Choice 67 4.3 Delivery Systems for the
Pediatric Population 69 4.3.1 Nebulizers 69 4.3.2 Pressurized Metered Dose
Inhalers 72 4.3.3 Dry Powder Inhalers 73 4.3.4 Interfaces 74 4.4
Recommendations 80 4.5 Conclusion 82 References 82 5. Formulation
Strategies for Pulmonary Delivery of Poorly Soluble Drugs 87 Nathalie
Wauthoz and Karim Amighi 5.1 Introduction 88 5.1.1 In vivo Fate of Inhaled
Poorly Water-soluble Drugs 89 5.1.2 The Pharmacokinetics of Inhaled Poorly
Water-soluble Drugs Administered for Local and Systemic Action 92 5.1.3
Formulation Strategies for Pulmonary Delivery of Poorly Water-soluble Drugs
93 5.2 Co-solvents 93 5.3 Cyclodextrins 97 5.4 PEGylation 99 5.5 Reduction
of Size to Micro-/Nanoparticles 100 5.5.1 Nanocrystal Suspension 101 5.5.2
Nanocrystals in a Hydrophilic Matrix System 102 5.5.3 Nanoclusters 103 5.6
Solid Dispersion/Amorphization 103 5.7 Micelles 106 5.8 Liposomes 108 5.9
Solid Lipid Nanoparticles and Nanostructured Lipid Carriers 110 5.10
Conclusion 111 References 114 6. Lipidic Micro- and Nano-Carriers for
Pulmonary Drug Delivery - A State-of-the-Art Review 123 Yahya Rahimpour,
Hamed Hamishehkar, and Ali Nokhodchi 6.1 Introduction 124 6.2 Pulmonary
Drug Delivery 125 6.3 Liposomal Pulmonary Delivery 126 6.4 Nebulization of
Liposomes 126 6.5 Liposomal Dry-powder Inhalers 128 6.6 Solid Lipid
Microparticles in Pulmonary Drug Delivery 129 6.7 Solid Lipid Nanoparticles
in Pulmonary Drug Delivery 131 6.8 Nanostructured Lipid Carrier (NLC) in
Pulmonary Drug Delivery 133 6.9 Nanoemulsions in Pulmonary Drug Delivery
134 6.10 Conclusion and Perspectives 135 References 136 7. Chemical and
Compositional Characterisation of Lactose as a Carrier in Dry Powder
Inhalers 143 Rim Jawad, Gary P. Martin and Paul G. Royall 7.1 Introduction
144 7.2 Production of Lactose 145 7.3 Lactose: Chemical Forms, Solid-State
Composition, Physicochemical Properties 147 7.4 Epimerisation of Lactose
150 7.5 Analysis of Lactose 151 7.5.1 Powder X-ray Diffraction 152 7.5.2
Nuclear Magnetic Resonance 153 7.5.3 Infrared Spectroscopy 156 7.5.4
Differential Scanning Calorimetry 157 7.5.5 Polarimetry 158 7.6 The
Influence of the Chemical and Solid-State Composition of Lactose Carriers
on the Aerosolisation of DPI Formulations 159 7.7 Conclusions 163
References 163 8. Particle Engineering for Improved Pulmonary Drug Delivery
Through Dry Powder Inhalers 171 Waseem Kaialy and Ali Nokhodchi 8.1
Introduction 172 8.2 Dry Powder Inhalers 172 8.3 Particle Engineering to
Improve the Performance of DPIs 172 8.3.1 Crystallization 173 8.3.2
Spray-drying 174 8.3.3 Spray-freeze-drying 177 8.3.4 Supercritical Fluid
Technology 177 8.3.5 Pressure Swing Granulation (PSG) Technique 178 8.4
Engineered Carrier Particles for Improved Pulmonary Drug Delivery from Dry
Powder Inhalers 178 8.5 Relationships between Physical Properties of
Engineered Particles and Dry Powder Inhaler Performance 182 8.5.1 Particle
Size 182 8.5.2 Flow Properties 184 8.5.3 Particle Shape 185 8.5.4 Particle
Surface Texture 187 8.5.5 Fine Particle Additives 188 8.5.6 Surface Area
188 8.6 Conclusions 189 References 189 9. Particle Surface Roughness - Its
Characterisation and Impact on Dry Powder Inhaler Performance 199 Bernice
Mei Jin Tan, Celine Valeria Liew, Lai Wah Chan, and Paul Wan Sia Heng 9.1
Introduction 200 9.2 What is Surface Roughness? 200 9.3 Measurement of
Particle Surface Roughness 202 9.3.1 General Factors to Consider During a
Measurement 202 9.3.2 Direct Methods to Profile or Visualise Surface
Roughness 204 9.3.3 Indirect Measurement of Surface Roughness 206 9.4
Impact of Surface Roughness on Carrier Performance - Theoretical
Considerations 206 9.4.1 Mixing and Blend Stability 206 9.4.2 Drug-carrying
Capacity 207 9.4.3 Drug Adhesion 207 9.4.4 Drug Detachment 208 9.4.5
Particle Arrangement in Ordered Mixtures After the Addition of Fine
Excipient 209 9.5 Particle Surface Modification 210 9.5.1 Spray Drying 210
9.5.2 Solution Phase Processing 211 9.5.3 Crystallisation 213 9.5.4 Sieving
213 9.5.5 Fluid-bed Coating 213 9.5.6 Dry Powder Coating 213 9.6 Conclusion
215 References 215 10. Dissolution: A Critical Performance Characteristic
of Inhaled Products? 223 Ben Forbes, Nathalie Hauet Richer, and Francesca
Buttini 10.1 Introduction 223 10.2 Dissolution of Inhaled Products 224
10.2.1 Dissolution Rate 224 10.2.2 Dissolution in the Lungs 224 10.2.3 Case
for Dissolution Testing 225 10.2.4 Design of Dissolution Test Systems 226
10.3 Particle Testing and Dissolution Media 226 10.3.1 Particle Collection
226 10.3.2 Dissolution Media 229 10.4 Dissolution Test Apparatus 230 10.4.1
USP Apparatus 1 (Basket) 231 10.4.2 USP Apparatus 2 (Paddle) and USP
Apparatus 5 (Paddle Over Disc) 232 10.4.3 USP Apparatus 4 (Flow-Through
Cell) 232 10.4.4 Diffusion-Controlled Cell Systems (Franz Cell, Transwell,
Dialysis) 233 10.4.5 Methodological Considerations 234 10.5 Data Analysis
and Interpretation 235 10.5.1 Modelling 236 10.5.2 Comparing Dissolution
Profiles (Model-independent Method for Comparison) 237 10.6 Conclusions 237
References 238 11. Drug Delivery Strategies for Pulmonary Administration of
Antibiotics 241 Anna Giulia Balducci, Ruggero Bettini, Paolo Colombo, and
Francesca Buttini 11.1 Introduction 242 11.2 Antibiotics Used for the
Treatment of Pneumoniae 243 11.3 Antibiotic Products for Inhalation
Approved on the Market 244 11.4 Nebulisation 246 11.5 Antibiotic Dry
Powders for Inhalation 250 11.5.1 Tobramycin 251 11.5.2 Capreomycin 252
11.5.3 Gentamicin 253 11.5.4 Ciprofloxacin 254 11.5.5 Levofloxacin 255
11.5.6 Colistimethate Sodium 256 11.6 Device and Payload of Dose 256 11.7
Conclusions 258 References 258 12. Molecular Targeted Therapy of Lung
Cancer: Challenges and Promises 263 Jaleh Barar, Yadollah Omidi, and Mark
Gumbleton 12.1 Introduction 265 12.2 An Overview on Lung Cancer 266 12.3
Molecular Features of Lung Cancer 268 12.3.1 Tumor Microenvironment (TME)
269 12.3.2 Tumor Angiogenesis 269 12.3.3 Tumor Stromal Components 270
12.3.4 Pharmacogenetic Markers: Cytochrome P450 270 12.4 Targeted Therapy
of Solid Tumors: How and What to Target? 271 12.4.1 EPR Effect: A Rational
Approach for Passive Targeting 272 12.4.2 Toward Long Circulating
Anticancer Nanomedicines 273 12.4.3 Active/Direct Targeting 273 12.4.4
Overcoming Multidrug Resistance (MDR) 273 12.4.5 Antibody-Mediated
Targeting 274 12.4.6 Aptamer-Mediated Targeted Therapy 276 12.4.7 Folate
Receptor-Mediated Targeted Therapy 276 12.4.8 Transferrin-Mediated Targeted
Therapy 276 12.4.9 Targeted Photodynamic Therapy 277 12.4.10 Multimodal
Theranostics and Nanomedicines 278 12.5 Final Remarks 278 References 279
13. Defining and Controlling Blend Evolution in Inhalation Powder
Formulations using a Novel Colourimetric Method 285 David Barling, David
Morton, and Karen Hapgood 13.1 Introduction 286 13.1.1 Introduction to
Blend Pigmentation 287 13.1.2 Previous Work in the Use of Coloured Tracers
to Assess Powder Blending 288 13.1.3 Colour Tracer Properties and Approach
to Blend Analysis 288 13.2 Uses and Validation 290 13.2.1 Assessment of
Mixer Characteristics and Mixer Behaviour 290 13.2.2 Quantification of
Content Uniformity and Energy Input 293 13.2.3 Detection and Quantification
of Unintentional Milling during Mixing 295 13.2.4 Robustness of Method with
Tracer Concentration 295 13.3 Comments on the Applied Suitability and
Robustness in of the Tracer Method 296 13.4 Conclusions 297
Acknowledgements 297 References 297 14. Polymer-based Delivery Systems for
the Pulmonary Delivery of Biopharmaceuticals 301 Nitesh K. Kunda, Iman M.
Alfagih, Imran Y. Saleem, and Gillian A. Hutcheon 14.1 Introduction 302
14.2 Pulmonary Delivery of Macromolecules 302 14.3 Polymeric Delivery
Systems 303 14.3.1 Micelles 304 14.3.2 Dendrimers 305 14.3.3 Particles 305
14.4 Preparation of Polymeric Nano/microparticles 305 14.4.1 Emulsification
Solvent Evaporation 306 14.4.2 Emulsification Solvent Diffusion 307 14.4.3
Salting Out 307 14.5 Formulation of Nanoparticles as Dry Powders 308 14.5.1
Freeze-drying 308 14.5.2 Spray-drying 309 14.5.3 Spray-freeze-drying 309
14.5.4 Supercritical Fluid Drying 310 14.6 Carrier Properties 310 14.6.1
Size 310 14.6.2 Morphology 311 14.6.3 Surface Properties 311 14.7 Toxicity
of Polymeric Delivery Systems 311 14.8 Pulmonary Delivery of Polymeric
Particles 312 14.9 Conclusions 313 References 313 15. Quality by Design:
Concept for Product Development of Dry-powder Inhalers 321 Al Sayyed
Sallam, Sami Nazzal, Hatim S. AlKhatib, and Nabil Darwazeh 15.1
Introduction 322 15.2 Quality Target Product Profile (QTPP) 324 15.3
Critical Quality Attributes (CQA) 324 15.4 Quality Risk Management 325 15.5
Design of Experiments 326 15.6 Design Space 328 15.7 Control Strategies 328
15.8 Continual Improvement 329 15.9 Process Analytical
Technology/Application in DPI 329 15.10 Particle Size 329 15.11
Crystallinity and Polymorphism 330 15.12 Scale-up and Blend Homogeneity 331
15.13 Applying of QbD Principles to Analytical Methods 331 15.14 Conclusion
332 References 332 16. Future Patient Requirements on Inhalation Devices:
The Balance between Patient, Commercial, Regulatory and Technical
Requirements 339 Orest Lastow 16.1 Introduction 340 16.1.1 Inhaled Drug
Delivery 340 16.1.2 Patients 340 16.2 Requirements 341 16.2.1 Patient
Requirements 341 16.2.2 Technical Requirements 343 16.2.3 Performance
Requirements 345 16.3 Requirement Specifications 346 16.3.1 Requirement
Hierarchy 346 16.3.2 Developing the Requirements 347 16.4 Product
Development 350 16.5 Conclusions 351 References 352 Index 353