A Wiley Book Series
Series Editors:
Dennis Douroumis, University of Greenwich, UK
Alfred Fahr, Friedrich–Schiller University of Jena, Germany
Jűrgen Siepmann, University of Lille, France
Martin Snowden, University of Greenwich, UK
Vladimir Torchilin, Northeastern University, USA
Titles in the Series
Hot-Melt Extrusion: Pharmaceutical Applications
Edited by Dionysios Douroumis
Drug Delivery Strategies for Poorly Water-Soluble Drugs
Edited by Dionysios Douroumis and Alfred Fahr
Computational Pharmaceutics: Application of Molecular Modeling in Drug Delivery
Edited by Defang Ouyang and Sean C. Smith
Pulmonary Drug Delivery: Advances and Challenges
Edited by Ali Nokhodchi and Gary P. Martin
Novel Delivery Systems for Transdermal and Intradermal Drug Delivery
Edited by Ryan Donnelly and Raj Singh
Forthcoming titles:
In Vitro Drug Release Testing of Special Dosage Forms
Edited by Nikoletta Fotaki and Sandra Klein
Editor
Consulting Editors
This edition first published 2016
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Atul Kumar Agrawal, CSIR Central Drug Research Institute, Lucknow, India
Eusondia Arnett, Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, The Ohio State University, Columbus, OH, USA
Miriam Braunstein, Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, NC, USA
Francesca Buttini, Department of Pharmacy, University of Parma, Viale delle Scienze, Parma, Italy and Institute of Pharmaceutical Science, King's College London, London, UK
Hak-Kim Chan, Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia
Gaia Colombo, Department of Life Sciences and Biotechnology, University of Ferrara, Via Fossato di Mortara, Ferrara, Italy
Shyamal C. Das, School of Pharmacy, University of Otago, Dunedin, New Zealand
Robert DeLong, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
P. Bernard Fourie, Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
Lucila Garcia-Contreras, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Stefano Giovagnoli, Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy
Mercedes Gonzalez-Juarrero, Mycobacteria Research Laboratories, Microbiology Immunology and Pathology, Colorado State University, Fort Collins, CO, USA
Anuradha Gupta, CSIR Central Drug Research Institute, Lucknow, India
Richard Hafner, National Institute of Allergy and Infectious Disease and National Institutes of Health, Bethesda, MD, USA
Graham F. Hatfull, Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA
David L. Hava, Pulmatrix Inc., Lexington, MA, USA
Anthony J. Hickey, Discovery Sciences Technologies Group, RTI International, Research Triangle Park, NC, USA
Mary K. Hondalus, Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
Mariam Ibrahim, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Nitya Krishnan, MRC Centre for Molecular Bacteriology and Infection, Department of Medicine, Imperial College London, UK
Nitesh K. Kunda, Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA
Andre G. Loxton, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Kimiko Makino, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan
Amber A. McBride, Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA
David N. McMurray, Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University Health Science Center, College Station, TX, USA
Amit Misra, CSIR Central Drug Research Institute, Lucknow, India
Pavan Muttil, Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA
Edward A. Nardell, Division of Global Health Equity, Brigham and Women’s Hospital, Boston, MA, USA
Ruvandhi R. Nathavitharana, Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA
Sanketkumar Pandya, CSIR Central Drug Research Institute, Lucknow, India
Dominique N. Price, Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA
Rajeev Ranjan, CSIR Central Drug Research Institute, Lucknow, India
Maurizio Ricci, Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia, Perugia, Italy
Brian D. Robertson, MRC Centre for Molecular Bacteriology and Infection, Department of Medicine, Imperial College London, London, UK
Carlo Rossi, Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy
Madhur Sachan, CSIR Central Drug Research Institute, Lucknow, India
Samantha L. Sampson, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Larry S. Schlesinger, Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, The Ohio State University, Columbus, OH, USA
Aurélie Schoubben, Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy
Peter J. Stewart, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
Jean C. Sung, Pulmatrix Inc., Lexington, MA, USA
Hiroshi Terada, Niigata University of Pharmacy and Applied Sciences, Niigata, Japan
Reinhard Vehring, Department of Mechanical Engineering, University of Alberta, Edmonton, Alberta, Canada
Jennifer Wong, Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia
Ellen F. Young, Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, NC, USA
“As a physician, I have seen how much pain TB patients experience after months of treatment by intramuscular injection (IM). It is almost impossible to inject by IM after one month. I think that aerosol delivery is the future for TB drug delivery because it is directly delivered to the target organ, and it is even more important for patients who have a hard time to take pills. I believe that aerosol delivery of TB drug(s) will be a milestone in TB treatment if successful.” Li Liang, Vice Director Beijing Chest Hospital
Having plagued societies for centuries, tuberculosis (TB) is one of the oldest diseases known to man. While the first drug effective against TB was not developed until 1943, over the next three decades many additional anti-TB drugs were discovered and developed that significantly reduced morbidity and mortality. Yet today it is estimated that one-third of the world’s population is infected with Mycobacterium tuberculosis. The most recent World Health Organization’s report indicated that TB killed 1.5 million people in 2014, making it a larger cause of death than HIV/AIDS, which was responsible for 1.2 million deaths. Thus, despite the perception that tuberculosis is a disease of the past or a disease of only low-income countries, it remains a major global public health challenge that carries significant global and domestic disease burdens and risks. Because serious societal challenges remain, including extreme poverty, inequity, and disproportionate TB burdens in women and children, TB will remain a significant challenge for the foreseeable future. Furthermore, the face of TB is changing. While global numbers of new TB cases and TB deaths have decreased at an average rate of at least 2 percent per year, TB strains that are resistant to the most commonly used, inexpensive, and least-toxic TB drugs have been identified in almost every country. These multidrug-resistant TB (MDR-TB) strains as well as the growing numbers of the even more serious extensively drug-resistant TB (XDR-TB) strains have been reported from nearly all countries. MDR-TB and XDR-TB cases can be exceedingly difficult and expensive to diagnose and treat successfully.
One of the major barriers to treatment of MDR-TB today is the high cost of second-line drugs that may be 300 to 3000 times more expensive than first-line therapy. Second-line regimens which are administered for between 18 to 24 months are associated with significant adverse events that often lead to discontinuation of treatment. Despite prolonged treatment duration, these regimens are not associated with high cure rates and incomplete, sub-optimal therapy of MDR-TB likely contributes to emergence of XDR-TB. In the face of M. tuberculosis strains resistant to all known classes of anti-TB drugs, leaders in global public health are asking whether XDR-TB is signaling a return to a pre-antibiotic era in TB control. Thus the need for new TB drugs has never been more urgent. Importantly, the search for new regimens and alternative strategies requires a thorough understanding of the preparation and performance of dosage forms.
Recent important gains in TB discovery research, product development, and implementation science and regulatory approval of the first new TB drug in 30 years give reason for optimism. Systematic studies of the biological effects of TB infection are beginning to shed light on the complexity of the human immune response and the dynamic nature of the disease process. As the disease becomes better understood in terms of both pathogen and host molecular biology there is an opportunity for new pharmaceutical approaches based on the route and means of delivery of a range of novel therapeutic agents. New studies are identifying molecules that can be used to diagnose TB or provide the basis of new TB vaccine research strategies, as well as critical biological processes against which new drug targets can be identified. Indeed the current global TB pipeline has multiple candidates in clinical trials – but there are few novel molecular entities. Many more candidates with novel mechanisms of action and chemical diversity are needed to overcome historical drug development attrition rates and emergence of resistance.
In the past, natural products have played a pivotal role in antibiotic drug discovery with most antibacterial drugs being derived from a natural product or natural product lead. A key challenge in the development of natural products as drugs is to combine their inherent antibacterial properties with physicochemical properties that confer oral bioavailability, an attribute that is highly desirable for treatment of MDR-TB. Many drugs are lost to development due to lack of oral bioavailability. However, new approaches to TB drug delivery as described in the current volume have the potential to overcome this barrier. New developments in drug delivery systems and technologies open an exciting avenue that may potentially lead to the repurposing of old drugs and re-evaluation of potential new drugs hitherto thought undeliverable.
Finally, while BCG vaccine remains the world’s most widely used vaccine and protects children against disseminated TB and meningitis, its effectiveness in preventing disease in adults varies widely. New candidate vaccines are being developed that provide protection against disease and possibly infection in animal models. Since the battle between the pathogen and immune response in TB is fought out largely in the lung, it will be essential both to understand protective immune responses in the lung and how to deliver new vaccine candidates to generate protection in the lung. This is another of the key issues in TB treated in this book.
This is a timely volume addressing the application of pharmaceutical sciences and dosage-form design to the development of novel strategies for TB therapy. This volume is arranged to consider the nature of disease, immunological responses, vaccine and drug delivery, disposition and response. In addition to conventional treatments some novel approaches are presented that if successful would create rapid development pathways. The contributors are drawn from the relevant fields of microbiology, immunology, molecular biology, pharmaceutics, pharmacokinetics, and chemical and mechanical engineering. No doubt the knowledge shared by the authors will have a major impact upon development of urgently needed new tools to address the continuing global crisis of TB and the increasing threat of drug-resistant strains.
The series Advances in Pharmaceutical Technology covers the principles, methods and technologies that the pharmaceutical industry uses to turn a candidate molecule or new chemical entity into a final drug form and hence a new medicine. The series will explore means of optimizing the therapeutic performance of a drug molecule by designing and manufacturing the best and most innovative of new formulations. The processes associated with the testing of new drugs, the key steps involved in the clinical trials process and the most recent approaches utilized in the manufacture of new medicinal products will all be reported. The focus of the series will very much be on new and emerging technologies and the latest methods used in the drug-development process.
The topics covered by the series include the following:
An evaluation of the current analytical methods used to determine drug stability, as well as the quantitative identification of impurities, contaminants and adulterants in pharmaceutical materials will be described, as will the production of therapeutic bio-macromolecules, bacteria, viruses, yeasts, moulds, prions and toxins through chemical synthesis and emerging synthetic/molecular biology techniques. The importance of packaging including the compatibility of materials in contact with drug products and their barrier properties will also be explored.
Advances in Pharmaceutical Technology is intended as a comprehensive one-stop shop for those interested in the development and manufacture of new medicines. The series will appeal to those working in the pharmaceutical and related industries, both large and small, and will also be valuable to those who are studying and learning about the drug-development process and the translation of those drugs into new life-saving and life-enriching medicines.
Tuberculosis remains the world’s most serious cause of disease due to a single infectious micro-organism. Despite the development of a vaccine almost a century ago and with the advent of drug treatment in the intervening period we appear to be no closer to eradicating this disease. New vaccine antigens and novel drugs have been the major focus in prevention and treatment of tuberculosis. While great effort has been expended and progress has been made in drug therapy it has occurred at a remarkably slow pace. Indeed, the challenges posed by multiple and extensively drug-resistant disease and co-infection with human immuno-deficiency virus have rendered the need for novel approaches urgent.
As the disease becomes better understood in terms of both pathogen and host molecular biology there is an opportunity for new pharmaceutical approaches based on the route and means of delivery of a range of novel therapeutic agents.
This volume is arranged to consider the nature of disease, immunological responses, vaccine and drug delivery, disposition and response. In addition to conventional treatments some novel approaches are presented that, if successful, would create rapid development pathways. The contributors are drawn from the relevant fields of microbiology, immunology, molecular biology, pharmaceutics, pharmacokinetics, and chemical and mechanical engineering.
The role of therapeutic targeting strategy, dosage-form design and route of administration in the effective treatment of tuberculosis has been a topic of personal interest that we have shared for approaching twenty years and it is our privilege to be able to bring current thinking on a range of topics into one volume. We owe a great deal to our friends and colleagues most of whom are authors of chapters in this volume who attended the meetings on ‘Inhaled Tuberculosis Therapy’ held in New Delhi and Tokyo in 2009 and 2013, respectively. Without their insight, enthusiasm and encouragement we would not have been able to complete this text.
It has been a great pleasure working with the staff at Wiley on the preparation of the book and we are particularly grateful for the contributions of Samanaa Srinivas, Emma Strickland and Rebecca Stubbs. Many thanks for their patience and accommodation throughout the process.