Inhaled Medicines: Optimizing Development through Integration of In Silico, In Vitro and In Vivo Approaches

Inhaled medicines are widely used to treat pulmonary and systemic diseases. The efficacy and safety of these medicines can be influenced by the deposited fraction, the regional deposition pattern within the lungs and by post-depositional events such as drug dissolution, absorption and clearance from the lungs. Optimizing performance of treatments thus requires that we understand and are able to quantify these product and drug attributes.

Inhaled Medicines: Optimizing Development through Integration of In Silico, In Vitro and In Vivo Approaches explores the current state of the art with respect to inhalation drug delivery, technologies available to assess product performance, and novel in silico methods now available to link in vitro product performance to clinical performance. Recent developments in the latter field, especially the prospect of integration of three-dimensional Computational Fluid Particle Methods (3D-CFPD) with physiologically based pharmacokinetic (PBPK models), unlocks the potential for in silico population studies that can help inform and optimize treatment and product development strategies. In this highly multidisciplinary field, where progress occurs at the intersection of several disciplines of engineering and science, this work aims to integrate current knowledge and understanding and to articulate a clear vision for future developments.

 

• Considers the healthcare needs driving the field, and where inhaled drugs could have the maximum impact
• Gives a concise account of the state of the art in key areas and technologies such as device and formulation technologies, clinically relevant in vitro performance assessment, medical imaging, as well as in silico modelling and simulation
• Articulates how the combination of in vitro product performance data, medical imaging and simulations technologies in the framework of large scale in silico pre-clinical trials could revolutionize the field
• Provides systematic and thorough referencing to sources offering a more-in-depth analysis of technical issues

Stavros Kassinos is Professor, Computational Sciences Laboratory, University of Cyprus and Computational Science Leader at the University of Cyprus. His research interests center on turbulence and the simulation and modelling of complex physical systems. The overall goal of his research is the understanding of fundamental processes in complex fluid flows and the application of this understanding to the development of new simulation methods in engineering applications. Areas of interest include transport and dispersion in turbulent flows, biological flows with emphasis on inhalation drug delivery, MHD turbulent and laminar flows, and environmental flows. He has been the chair of COST Action MP1404 – “SimInhale”, which has inspired this book. He has served as visiting faculty in the Department of Radiology of the Stanford School of Medicine. Previously, he has worked in the Mechanical Engineering Department at Stanford University as a Postdoctoral Fellow, and as Senior Research Staff at the Stanford/NASA-Ames Center for Turbulence Research (CTR). He held a joint appointment at the Center for Integrated Turbulence Simulations (CITS) at Stanford University. He also holds a Ph.D. from Stanford University.Stavros Kassinos is Professor, Computational Sciences Laboratory, University of Cyprus and Computational Science Leader at the University of Cyprus. His research interests center on turbulence and the simulation and modelling of complex physical systems. The overall goal of his research is the understanding of fundamental processes in complex fluid flows and the application of this understanding to the development of new simulation methods in engineering applications. Areas of interest include transport and dispersion in turbulent flows, biological flows with emphasis on inhalation drug delivery, MHD turbulent and laminar flows, and environmental flows. He has been the chair of COST Action MP1404 – “SimInhale”, which has inspired this book. He has served as visiting faculty in the Department of Radiology of the Stanford School of Medicine. Previously, he has worked in the Mechanical Engineering Department at Stanford University as a Postdoctoral Fellow, and as Senior Research Staff at the Stanford/NASA-Ames Center for Turbulence Research (CTR). He held a joint appointment at the Center for Integrated Turbulence Simulations (CITS) at Stanford University. He also holds a Ph.D. from Stanford University.

Dr Bäckman is senior inhalation consultant at Emmace Consulting AB in Lund Sweden. He is currently focused on the development and application of computer based mechanistic models and in vivo predictive test methods to understand critical product attributes and their influence on the disposition of orally inhaled therapeutics. This includes the impact of dose, aerosol quality and drug dissolution on the rate and extent of drug absorption from the airways. Dr Bäckman holds a PhD from the University of Lund and has been actively engaged in research and development of inhaled therapeutics since 1995. He is also the current co-chair of the Product Quality Research Institute (PQRI) sponsored working group laying the foundation for an inhaled biopharmaceutical classification system.

Professor Joy Conway is the Professor of Respiratory Sciences, Centre for Health, Medicine and Life Sciences, Brunel University London. Joy has extensive experience as a reseracher and educator with over 25 years in UK Higher Education Institutions. Joy has a strong interest in lung disease, care of those with lung disease, respiratory physiology and pathophysiology and lung imaging. Following qualification as a chartered physiotherapist and a Masters in Rehabilitation (University of Southampton) her PhD (University of Southampton) investigated the use of three-dimensional lung imaging techniques to quantify inhaled aerosol deposition in the lung and structural and functional changes that occur with disease. Joy then progressed through to a personal Chair at the University of Southampton in 2009. In 2019 Joy was appointed as Professor at Brunel University London. At Brunel she is divisional research lead and a Director of the Smart Technologies Advancements for Health and Rehabilitation (STAHR) Research Centre. She is also the national research lead for advancing practice for Health Education England (2019 -) and maintains visiting Professor status with the NIHR Southampton Biomedical Research Centre for Respiratory and Critical Care (2019 -). Joy has extensive expertise in multi-modality, clinical imaging technologies and taking innovations to prototype and patent development. She brings experience in the integration of advanced technologies in healthcare, bridging the academic and health divide. Joy has acted as scientific advisor to several companies.

Dr. Hickey is Distinguished RTI Fellow, at the Research Triangle Institute and Director of the UNC Catalyst for Rare Diseases of the Eshelman School of Pharmacy He obtained Ph.D. and D.Sc. degrees in pharmaceutical sciences from Aston University, Birmingham, UK. He is a Fellow of the Royal Society of Biology, the American Association of Pharmaceutical Scientists, the American Association for the Advancement of Science and the Royal Society of Medicine. He received the Research Achievement Award of the Particulate Presentations and Design Division of the Powder Technology Society of Japan, the Distinguished Scientist Award of the American Association of Indian Pharmaceutical Scientists; the David W Grant Award in Physical Pharmacy of the American Association of Pharmaceutical Scientists; Thomas T Mercer Joint Prize for Excellence in Inhaled Medicines and Pharmaceutical Aerosols of the American Association for Aerosol Research and the International Society for Aerosols in Medicine and the Ralph Shangraw Memorial Award for Excipient and Excipient Technology of the International Pharmaceutical Excipient Consortium Foundation. He is founder (and formerly President and CEO) of Cirrus Pharmaceuticals, Inc., acquired by Kemwell Pharma; founder (formerly CSO, 2002-2007) of Oriel Therapeutics, Inc, acquired by Sandoz and founder and CEO of Astartein, Inc.; member of the Pharmaceutical Dosage Forms Expert Committee of the United States Pharmacopeia and formerly Chair of the Aerosols Expert Committee of the USP. Dr. Hickey conducts multidisciplinary research programs in the field of pulmonary drug and vaccine delivery for the treatment and prevention of a variety of diseases and oversees research in target and candidate therapeutic agent identification for rare and neglected diseases.