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. INDICE: List of Contributors .Series Preface .Preface .1. Lung anatomy and physiology and their implications for pulmonary drug delivery Lucila Garcia–Contreras, Mariam Ibrahim and Rahul Verma .1.1 Introduction .1.2 Anatomy and physiology of lungs 1.2.1 Macro and microstructure of the airways and alveoli as it pertains to drug delivery .1.2.2 Lung surfactant .1.2.3 Pulmonary blood circulation .1.3 Mechanisms of aerosol deposition .1.3.1 Impaction .1.3.2 Sedimentation .1.3.3 Interception .1.3.4 Diffusion .1.4 Drug absorption .1.4.1 Mechanisms of drug absorption from the lungs .1.5 Physiological factors affecting the therapeutic effectiveness of drugs delivered by the pulmonary route .1.5.1 Airway geometry .1.5.2 Inhalation mode .1.5.3 Air flow rate .1.5.4 Mechanism of particle clearance .1.5.5 Lung receptors .1.5.6 Disease states .1.5.7 Effect of age and gender difference .1.6 Computer simulations to describe aerosol deposition in health and disease .1.6.1 Semi–empirical models .1.6.2 Deterministic models .1.6.3 Trumpet models .1.6.4 Stochastic models .1.6.5 Computation fluid dynamics (CFD) based model .1.7 Conclusions .References .2. The role of functional lung imaging in improvement of pulmonary drug delivery Stephen Dubsky and Andreas Fouras. .3. Contemporary review of pulmonary delivery: recent advances and continuing challenges Robert O. (Bill) Williams III and Simone Raffa Carvalho. .3.1 Introduction .3.2 Dry Powder Inhaler Devices .3.2.1 Overview .3.2.2 Recent Innovations in Dry Powder Inhaler Technology .3.3 New developments in DPI formulations and delivery .3.3.1 Particle surface modification .3.3.2 Particle Engineering Technology for Pulmonary Delivery .3.3.2.1 Spray drying .3.3.2.2 Spray–freezing methods .3.3.2.3 Thin film Freezing .3.3.2.4 Sono–crystallization .3.3.2.5 Fixed–Dose Drug Combination .3.3.2.6 Nanoparticles and Biodegradable Polymeric Nanocarriers .3.3.2.7 Controlled Release of Drugs for Lung Delivery .3.3.2.8 Macromolecules for Pulmonary Delivery .3.4 Characterization Methods of Dry Powder Inhaler Formulations .3.5 Conclusion .4. Pulmonary drug delivery to the paediatric population – a state of the art review Marie–Pierre Flament .4.1. Introduction .4.2. Patient considerations .4.2.1. Anatomy and physiology of children s lungs .4.2.2. Nasal versus oral inhalation .4.2.3. Patient–related factors influencing aerosol deposition .4.2.4. Age and dosage forms of choice .4.3. Delivery systems for the paediatric population .4.3.1. Nebulizers .4.3.2. Pressurized Metered Dose Inhalers (pMDIs) .4.3.3. Dry Powder Inhalers (DPI) .4.3.4. Interfaces .4.3.4.1. Facemask .4.3.4.2. Spacers/Valve holding chambers .4.3.4.3. Hoods .4.4. Recommendations .4.5. Conclusion .5. Formulation strategies for pulmonary delivery of poorly soluble drugs Christophe Duret, Nathalie Wauthoz and Karim Amighi .5.1. Co–solvents .5.2. Cyclodextrins .5.3. PEGylation .5.4. Reduction of size to micro–/nanoparticles .Nanocrystal suspension .Nanocrystals in a hydrophilic matrix system .Nanoclusters .5.5. Solid dispersion/amorphization .5.6. Micelles .5.7. Liposomes .5.8. Solid lipid nanoparticles and nanostructured lipid carriers .Conclusion .6. Lipidic micro and nanoparticles for pulmonary drug delivery– a state of the art review Hamed Hamishekar, Yahya Rahimpour and Ali Nokhodchi .7. Chemical and compositional characterization of lactose as a carrier in dry powder inhalers Rim Jawad, Gary Martin and Paul Royall .8. Particle engineering for improved pulmonary drug delivery through dry powder inhalers Waseem Kaialy and Ali Nokhodchi .8.1 Introduction .8.2 Dry powder inhalers .8.3 Particle engineering to improve the performance of DPIs .8.3.1 Crystallization .8.3.2 Spray drying .8.3.3 Spray freeze drying .8.3.4 Super critical fluid (SCF) technology .8.3.4.1 Rapid Expansion of Supercritical fluid Solution (RESS) .8.3.4.2 Gas Antisolvent (GAS) recrystallization .8.3.4.3 Solution Enhanced Dispersion by SCF (SEDS) .8.3.4.4 Precipitation from Gas Saturated Solutions (PGSS) .8.3.4.5 Pressure swing granulation (PSG) technique .8.4 Engineered carrier particles for improved pulmonary drug delivery through dry powder inhalers .8.5 Relationships between physical properties of engineered particles and dry powder inhaler performance .8.5.1 Particle size .8.5.2 Flow properties .8.5.3 Particle Shape .8.5.4 Particle surface texture .8.5.5 Fine Particle additives .8.5.6 Surface area .8.6 Conclusions .8.7 References .9. Impact of particle surface roughness on dry powder inhaler performance Bernice M J Tan, Celine V Liew, L W Chan and Paul W S Heng .9.1 Introduction .9.2 What is surface roughness? .9.3 Measurement of particle surface roughness .9.3.1 General factors to consider during a measurement .9.3.1.1 Particle size .9.3.1.2 Measurement conditions .9.3.1.3 Image–processing operations .9.3.1.4 Selection of roughness parameters .9.3.2 Direct methods to profile or visualize surface roughness .9.3.2.1 Surface profiling by atomic force microscopy .9.3.2.2 Non–contact surface profiling by optical methods .9.3.2.3 Surface imaging by scanning electron microscopy .9.3.3 Indirect measurement of surface roughness .9.3.3.1 Determination of surface area .9.4 Impact of surface roughness on carrier performance theoretical considerations .9.4.1 Mixing and blend stability .9.4.2 Drug–carrying capacity .9.4.3 Drug adhesion .9.4.4 Drug detachment .9.4.5 Particle arrangement in ordered mixtures after addition of fine excipient .9.5 Particle surface modification .9.5.1 Spray drying .9.5.2 Solution phase processing .9.5.2.1 Temperature–controlled dissolution and wet decantation .9.5.2.2 Manipulation of relative humidity .9.5.2.3 Particle smoothing in a high shear mixer .9.5.3 Crystallization .9.5.4 Sieving .9.5.5 Fluid–bed coating .9.5.6 Dry powder coating .9.5.6.1 By vigorous mixing .9.5.6.2 By mechanofusion .9.6 Conclusion .References .10. Dissolution – a critical performance characteristic of inhaled products? Ben Forbes1 and Francesca Buttini2 .10.1 Introduction .10.2 Dissolution of inhaled products .10.2.1. Dissolution rate .10.2.2. Dissolution in the lungs .10.2.3. The case for dissolution testing .10.2.4. The design of dissolution test systems .10.3 Particle collection and dissolution media .10.3.1. Particle collection .10.3.2. Dissolution media .10.4 Dissolution apparatus .10.4.1. USP apparatus 1 (Basket) .10.4.2. USP apparatus 2 (Paddle) and USP apparatus 5 (paddle over disk) .10.4.3. USP Apparatus 4 (Flow through cell) .10.4.4. Diffusion controlled cell systems (Franz cell, Transwell, Dialysis) .10.4.5. Methodological considerations .10.5 Data analysis and interpretation .10.5.1. Modeling .10.5.2. Equivalence .10.6 Conclusion .11. Drug delivery strategies for pulmonary administration of antibiotics Paolo Colombo, Anna Giulia Balducci, Ruggero Bettini and Francesca Buttini .12. Molecular targeted therapy of lung cancer: challenges and promises Jaleh Barar1, Yadollah Omidi1, and Mark Gumbleton2 .Introduction .An overview on lung cancer .Molecular features of lung cancer .Tumor microenvironment (TME) .Tumor angiogenesis .Tumor stromal components .Pharmacogenetics markers: cytochrome P450 .Targeted therapy of solid tumors: how and what to target? .EPR effect: a rational approach for passive targeting .Towards long circulating anticancer nanomedicines .Active/direct targeting .Overcoming multi–drug resistance (MDR) .Antibody–mediated targeting .Aptamer–mediated targeted therapy .Folate receptor–mediate targeted therapy .Transferrin–mediate targeted therapy .Targeted photodynamic therapy .Multimodal theranostics and nanomedicines .Final remarks .13. Defining and controlling blend evolution in inhalation powder formulations using a novel colorimetric method David Barling, David Morton and Karen Hapgood .Abstract .List of abbreviations in chapter .13.1 Introduction .13.1.1 Introduction to blend pigmentation .13.1.2 Previous work in the use of coloured tracers to assess powder blending .13.1.3 Colour tracer properties and approach to blend analysis .13.2 Uses and validation .13.2.1 Assessment of mixer characteristics and mixer behaviour .13.2.2 Quantification of content uniformity and energy input .13.2.3 Detection and quantification of unintentional milling during mixing .13.2.4 Robustness of method with tracer concentration .13.3 Comments on the applied suitability and robustness in of the tracer method .Acknowledgements .References .14. Polymer–based delivery systems for the pulmonary delivery of macromolecules Nitesh Kunda 1, Iman M. Alfagih1,2, Imran Saleem1 and Gillian A. Hutcheon1 .15. Quality by design: concept for the product development of dry powder inhalers Al–Sayed Sallam1, Sami Nazzal2, Hatim Al Khatib3 and Nabil Darwazeh4 .16. Future patient requirements of inhalation devices the balance between patient, commercial, regulatory and technical requirements Orest Lastow .Index
- ISBN: 978-1-118-79954-3
- Editorial: Wiley–Blackwell
- Encuadernacion: Cartoné
- Páginas: 384
- Fecha Publicación: 24/07/2015
- Nº Volúmenes: 1
- Idioma: Inglés