3rd Edition

Pharmaceutical Inhalation Aerosol Technology, Third Edition

Edited By Anthony J. Hickey, Sandro R. da Rocha Copyright 2019
    746 Pages 200 B/W Illustrations
    by CRC Press

    746 Pages 200 B/W Illustrations
    by CRC Press

    This fully revised and updated third edition of Pharmaceutical Inhalation Aerosol Technology encompasses the scientific and technical foundation for the rationale, design, componentry, assembly and quality performance metrics of therapeutic inhalers in their delivery of pharmaceutical aerosols to treat symptoms or the underlying causes of disease. It focuses on the importance of pharmaceutical engineering as a foundational element of all inhaler products and their application to pulmonary drug delivery. The expanded scope considers previously unaddressed aspects of pharmaceutical inhalation aerosol technology and the patient interface by including aerosol delivery, lung deposition and clearance that are used as measures of effective dose delivery.

    Key Features:

    • Provides a thoroughly revised and expanded reference with authoritative discussions on the physiologic,pharmacologic, metabolic, molecular, cellular and physicochemical factors, influencing the efficacy and utilization of pharmaceutical aerosols

    • Emphasizes the importance of pharmaceutical engineering as a foundational element of all inhaler products and their application to pulmonary drug delivery

    • Addresses the physics, chemistry and engineering principles while establishing disease relevance

    • Expands the ‘technology’ focus of the original volumes to address the title more directly

    • Offers an impressive breadth of coverage as well as an international flavour from outstanding editors and contributors

    1. Introduction

    Anthony J. Hickey and Sandro R.P. da Rocha

    Section I Discovery (pharmacology/physiology/anatomy, etc)

    2. Physiology of the Airways

    Anthony J. Hickey and David C. Thompson

    3. Drug Targeting to the Lung: Chemical and Biochemical Considerations

    Peter A. Crooks, Narsimha R. Penthala, and Abeer M. Al-Ghananeem

    Section II Aerosol Critical Attributes (aerodynamic

    behaviour, lung deposition, and clearance)

    4. Aerosol Physics and Lung Deposition Modelling

    Warren H. Finlay

    5. Practical Aspects of Imaging Techniques Employed to Study Aerosol Deposition and

    Clearance Myrna B. Dolovich

    6. Pharmacokinetics and Pharmacodynamics of Drugs Delivered to the Lung

    Stefanie K. Drescher, Mong-Jen Chen, Jürgen B. Bulitta, and Günther Hochhaus

    Section III Active Pharmaceutical

    Ingredient/Drug Product Manufacturing

    7 Small Molecules: Process Intensification and Continuous Synthesis

    Thomas D. Roper

    8 Biologic Drug Substance and Drug Product Manufacture

    Ajit S. Narang, Mary E. Krause, Shelly Pizarro, and Joon Chong Yee

    9 Scale-Up Considerations for Orally Inhaled Drug Products

    Jeremy Clarke and S. van den Ban

    10 Quality by Control Helen N. Strickland and Beth Morgan

    Section IV Particle Engineering/Processing (milling/blending,

    spray drying, supercritical fluid, nano, etc.)

    11. Milling and Blending: Producing the Right Particles and Blend Characteristics for

    Dry Powder Inhalation Bernice Mei Jin Tan, Lai Wah Chan, and Paul Wan Sia Heng

    12. Engineering Stable Spray Dried Biologic Powder for Inhalation

    Nicholas Carrigy and Reinhard Vehring

    13 Supercritical Fluid Manufacture

    Ana Aguiar-Ricardo and Eunice Costa

    14 Particle Engineering Technology for Inhaled Therapies

    David Lechuga-Ballesteros, Susan Hoe, and Ben Maynor

    Section V Drug Product Formulation

    15 Emerging Pulmonary Delivery Strategies in Gene Therapy: State of the Art and

    Future Considerations G. Costabile and Olivia M. Merkel

    16 Genome Editing for Genetic Lung Diseases

    Ying Zhang and Hao Yin

    17 Inhalation Drug Products Containing Nanomaterials

    Sandro R.P. da Rocha, Rodrigo S. Heyder, Elizabeth R. Bielski, Ailin Guo, Martina

    Steinmaurer, and Joshua J. Reineke

    Section VI Devices (design and performance)

    18. Pressurized Metered-Dose Inhalers

    Sandro R. P. da Rocha, Balaji Bharatwaj, Rodrigo S. Heyder, and Lin Yang

    19. Dry Powder Inhalation

    A. H. de Boer and F. Grasmeijer

    20. Nebulisers John N. Pritchard, D. von Hollen, and R. H. M. Hatley

    21. Soft Mist Sprays

    Stefan Leiner, David Cipolla, Joachim Eicher, Wilbur de Kruijf, and Herbert Wachtel

    Section VII Drug Product Testing (physico-chemical properties,

    aerodynamic particle size, delivered dose, etc.)

    22 Quality by Design Considerations

    William Craig Stagner and Anthony J. Hickey

    23 Solid State Testing of Inhaled Formulations

    Philip Chi Lip Kwok and Hak-Kim Chan

    24 Aerodynamic Particle Size Testing

    Jolyon Mitchell

    Section VIII Regulatory Considerations (CMC)

    25. Scanning the Intricate Regulatory Landscape and Trying to Peek Over the Horizon

    Steve T. Horhota, Stefan Leiner, and A. T. Horhota

    26. Pharmacopeial and Regulatory Guidances on Product Quality and Performance

    Anthony J. Hickey

    27. The European Union Regulatory Scene

    Steven C. Nichols and Dennis Sandell

    Section IX Preclinical Testing (dosing for cells and animals)

    28. Cell- and Tissue-Based (Reconstituted) 2D In Vitro Models to Study Drug Transport

    Processes across the Air-Blood Barrier Nicole Schneider-Daum, Patrick Carius, Justus C. Horstmann, and Claus-Michael Lehr

    29. 3D In Vitro/Ex Vivo Systems

    Bethany M. Young, Alexandria Ritchie, Laleh Golshahi, and Rebecca L. Heise

    30. Preclinical Models for Pulmonary Drug Delivery

    J. P. Ibrahim, R. J. Bischof, and M. P. McIntosh

    Section X Clinical Testing (concepts of bioequivalence)

    31. Bioequivalence of Orally-Inhaled Drug Products: Challenges and Opportunities

    Jayne E. Hastedt and Elise Burmeister Getz

    32. General Conclusions

    Anthony J. Hickey and Sandro R. P. da Rocha



    Dr. Hickey is a Distinguished Fellow at the Research Triangle Institute, Emeritus Professor of Molecular Pharmaceutics of the Eshelman School of Pharmacy (2010-present, Professor 1993-2010) and Adjunct Professor Biomedical Engineering in the School of Medicine, at the University of North Carolina at Chapel Hill. He obtained Ph.D. (1984) and D.Sc. (2003) degrees in pharmaceutical sciences from Aston University, Birmingham, UK. Following postdoctoral positions, at the University of Kentucky (1984-1988) Dr. Hickey joined the faculty at the University of Illinois at Chicago (1988-1993). In 1990 he received the AAPS Young Investigator Award in Pharmaceutics and Pharmaceutical Technology. He is a Fellow of the Royal Society of Biology (2000), the American Association of Pharmaceutical Scientists (2003) and the American Association for the Advancement of Science (2005). He is the founder (1997, and formerly President and CEO, 1997-2013) of Cirrus Pharmaceuticals, Inc., which was acquired by Kemwell Pharma in 2013; founder (2001, and formerly CSO, 2002-2007) of Oriel Therapeutics, Inc, which was acquired by Sandoz in 2010 and founder and CEO of Astartein, Inc. (2013-present); member of the Pharmaceutical Dosage Forms Expert Committee of the United States Pharmacopeia (USP, 2010–2015, Chair of the sub-committee on Aerosols) and formerly Chair of the Aerosols Expert Committee of the USP (2005-2010). Dr. Hickey conducts a multidisciplinary research program in the field of pulmonary drug and vaccine delivery for treatment and prevention of a variety of diseases.

    Dr. da Rocha is an Associate Professor of Pharmaceutics in the School of Pharmacy, holds a joint appointment in Chemical and Life Science Engineering, and is also a member of the Massey Cancer Center at Virginia Commonwealth University (VCU). He obtained his Ph.D. in 2000 from the University of Texas at Austin in Chemical Engineering. After a postdoctoral position in Chemistry and Biochemistry also at the University of Texas at Austin, Dr. da Rocha joined the faculty at Wayne State University in Detroit, MI, where he worked until 2015. Prof. da Rocha has provided significant contribution to the area of pulmonary drug delivery, particularly through the development of novel pressurized metered dose inhaler formulations and of nanotherapeutics for pulmonary drug delivery, both areas having potential applications in the treatment of a variety of pulmonary disorders. Prof. da Rocha has written a number of manuscripts, book chapters, and disclosed several technologies with his collaborators (visiting faculty, postdoctoral fellows, Ph.D., undergraduate, graduate and high-school students), many of them now working in the industry and government in areas related to pulmonary drug delivery. Prof. da Rocha is the School of Pharmacy Director for the Pharmaceutical Engineering Program at VCU.

    This is a comprehensive reference on the scientific and regulatory aspects of inhaled aerosol drug delivery systems. The field of pharmaceutical aerosols has been growing. This edition is expected to be well received by the audience. There are only a couple of books on this subject, but they are not comprehensive. Therefore, this is a must-have reference for scientists working in this field.

    - Rahmat M. Talukder, The University of Texas at Tyler