Numerous phenomenal advances have been made towards understanding the role of neurotransmitters in the pathophysiology of neurological disorders, and these have resulted in a large number of novel molecules with the potential to revolutionize the treatment and prevention of such disorders. This book provides a comprehensive and detailed explanation of brain neurotransmitters and their receptors and associated channels. It includes a basic introduction, and also discusses the functions and recent advances and their pharmacology, highlighting the role of various computer aided drug design (CADD) strategies for the development of therapeutic ligands to modulate these receptors/ion channels. Written in an easy-to-read style, it is intended for neuroscience and pharmaceutical students and researchers working in the area of brain neurotransmitters.

Completely dedicated to the biomedical applications of metal nanoparticles, this book covers the different toxicity problems found in healthcare situations and also provides comprehensive info on the use of metal nanoparticles in treating various diseases. Metal Nanoparticles in Pharma is the first edited volume to set up the discussion for a clinical setting and to target a pharmaceutical audience of academic and industry-based researchers.

This book explores the possible development of neurokinin-3 receptor (NK3R) antagonists with reduced environmental impact. Pharmaceuticals are used to cure diseases and to alleviate symptoms in humans and animals. However, the stable, bioactive substances excreted by patients have unfavorable effects on non-target species. To overcome these disadvantages of these highly stable, potent substances, drug design to turn off bioactivity after release into the environment is needed. The book describes the development of eco-friendly NK3R antagonists by introducing a labile functional moiety and substituting a scaffold. This resulted in a novel NK3R antagonist that oxidized into its inactive form when exposed to air. Further, the book presents an efficient and easily achievable synthetic method of creating triazolopiperazine scaffolds, as well as a structure-activity relationship study involving scaffold hopping for decomposable motifs, which led to a novel photodegradable NK3R antagonist. Demonstrating that it is possible to develop compounds that convert into their inactive forms under environmental conditions, this book is useful for anyone interested in therapeutic agents with reduced environmental impact.

The content of this book is intended to provide the toxicologist in drug development in the pharmaceutical and biotechnology industries with a broad understanding of bone and its interactions with other organ systems in safety assessments. The book is divided into three parts. The first part describes our current understanding of bone biology and its primary regulatory pathways. Additional chapters address regulatory and study design considerations for incorporating bone end points in toxicology studies, with special consideration being given to juvenile toxicology studies. This is intended to address recent regulatory requirements to evaluate skeletal development for drugs in development for pediatric populations. The second part of the book describes the principal techniques and methods used in bone research; understanding how these end-points are derived is fundamental to their appropriate application. These first two parts of the book provide the background and the means to develop the concepts in part three which describes bone and its interaction with other organ systems. The unique series of chapters in part three, contributed to by key leaders in their respective fields and in bone research, provides a comprehensive collective work. Although constantly evolving, the crosstalk and interaction of the skeleton with several organ systems is now recognized and well documented, such as for the reproductive system, muscle and kidney, while our understanding of the interaction with other organ systems, such as the immune system and CNS, is in its infancy. Recent work highlights the key role of the skeleton in the regulation of energy metabolism and the impact this has on research in metabolic diseases such as obesity and diabetes. The hope is that this book will enlighten many and encourage more to explore the impact of new compounds on the skeleton in the development of effective and safe drugs.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

This book aims to address the major aspects of future drug product development and therapy for older adults, giving practical guidance for the rational product and clinical development and prescribing of drug products to this ever growing segment of the population. With authors coming from key "aging" markets such as Europe, the USA, China and Japan, the book will provide valuable information for students, scientists, regulators, practitioners, and other healthcare professionals from academia, industry and regulatory bodies.

Antimicrobial resistance is a major global public health problem. This book focuses on the clinical implications of multi-drug resistant pathogens; tracking AMR and its evolutionary significance; antifungal resistance; and current and alternative treatment strategies for AMR, including antivirulent, antibiofilm and antimicrobial resistance breakers, repurposing of drugs, and probiotic therapy. Advances in antimicrobial stewardship, antibiotic policies from a global perspective and their impacts are also discussed. The book also explores the use of omics approaches to gain insights into antibacterial resistance, and includes chapters on the potential benefits of a 'One Health approach' describing the environmental and zoonotic sources of resistant genes and their effects on the global resistance pool.

This book volume provides complete and updated information on the applications of Design of Experiments (DoE) and related multivariate techniques at various stages of pharmaceutical product development. It discusses the applications of experimental designs that shall include oral, topical, transdermal, injectables preparations, and beyond for nanopharmaceutical product development, leading to dedicated case studies on various pharmaceutical experiments through illustrations, art-works, tables and figures. This book is a valuable guide for all academic and industrial researchers, pharmaceutical and biomedical scientists, undergraduate and postgraduate research scholars, pharmacists, biostatisticians, biotechnologists, formulations and process engineers, regulatory affairs and quality assurance personnel.

This book focuses on how to appropriately plan and develop a Phase II program, and how to design Phase II clinical trials and analyze their data. It provides a comprehensive overview of the entire drug development process and highlights key questions that need to be addressed for the successful execution of Phase II, so as to increase its success in Phase III and for drug approval. Lastly it warns project team members of the common potential pitfalls and offers tips on how to avoid them.

This contributed volume presents an overview of concepts, methods, and applications used in several quantitative areas of drug research, development, and marketing. Chapters bring together the theories and applications of various disciplines, allowing readers to learn more about quantitative fields, and to better recognize the differences between them. Because it provides a thorough overview, this will serve as a self-contained resource for readers interested in the pharmaceutical industry, and the quantitative methods that serve as its foundation. Specific disciplines covered include: Biostatistics Pharmacometrics Genomics Bioinformatics Pharmacoepidemiology Commercial analytics Operational analytics Quantitative Methods in Pharmaceutical Research and Development is ideal for undergraduate students interested in learning about real-world applications of quantitative methods, and the potential career options open to them. It will also be of interest to experts working in these areas.

This book explores efficient syntheses of indole alkaloids based on gold-catalyzed cascade cyclizations, presenting two strategies for total synthesis of these natural products based on gold-catalyzed reactions of conjugated diyne or ynamide. The book first describes the total and formal synthesis of dictyodendrins A-F based on direct construction of the pyrrolo[2,3-c]carbazole core using the gold-catalyzed annulation of azido-diynes and protected pyrrole. This synthetic strategy features late-stage functionalization of the pyrrolo[2,3-c]carbazole scaffold at several positions and allows diverse access to dictyodendrins and their derivatives. Secondly, the book discusses the formal synthesis of vindorosine based on the pyrrolo[2,3-d]carbazole construction using the gold-catalyzed cascade cyclization of ynamide. Importantly, the reaction using a chiral gold complex provides the optically active pyrrolo[2,3-d]carbazole. This strategy facilitates the rapid construction of the pyrrolocarbazole core structure of aspidosperma and related alkaloids, including vindorosine. These methodologies can accelerate the medicinal application of pyrrolocarbazole-type alkaloids and related compounds.

This handbook covers established and advanced techniques for biomarker analysis, such as guidelines and strategies for assay validation methods; different mathematical models that are necessary in contemporary drug discovery and development; and evaluation of new cytometry methods. Expertly curated by two practicing professionals in drug development and biotherapeutics, individual chapters are selected for novel and sound research; information is chosen based on its relevance to lab applications and clinical trials, such as the topic of selecting animal models for their relevancy to humans. The book is multifaceted, discussing the ethics and issues with biospecimens and providing an in-depth analysis to the differences between pre-clinical and clinical assay development. The book is an essential read for general readers who need an introduction to the history and background of biomarkers, and it also provides critical analyses of various new validation methods for practitioners and researchers.

Freeze-drying, in the past popular in the food industry, has more recently been adopted by the pharmaceutical industry as a standard method for the production of stable solid preparations. Freeze-drying of Pharmaceuticals and Biopharmaceuticals is the first book to specifically describe this process, as related to the pharmaceutical industry. The emphasis of this book is on the properties of the materials processed, how effective formulations are arrived at, and how they are stored and marketed. Beginning with a historical overview of the process, Freeze-drying of Pharmaceuticals and Biopharmaceuticals briefly describes the processes and equipment involved, including: the physics, chemistry and biochemistry associated with freezing, aspects of formulation development, primary and secondary drying; the economics and engineering of scaling up; and, most importantly, attributes of the dried product. It also discusses in detail the science behind freeze-drying, such as the properties of crystalline and amorphous solids. The book concludes with selected case studies and discusses the future of freeze-drying, advances in alternative drying methods, and concludes with an extensive bibliography. This book, written by a leading expert in the field, is aimed primarily at product and process developers in the biopharmaceutical industry and academia.

Translational medicine addresses the gap between research and the clinical application of new discoveries. To efficiently deliver new drugs to care centers, a preclinical evaluation, both in vitro and in vivo, is required to ensure that the most active and least toxic compounds are selected as well as to predict clinical outcome. Antimicrobial nanomedicines have been shown to have higher specificity in their therapeutic targets and the ability to serve as adjuvants, increasing the effectiveness of pre-existing immune compounds. The design and development of new standardized protocols for evaluating antimicrobial nanomedicines is needed for both the industry and clinical laboratory. These protocols must aim to evaluate laboratory activity and present models of pharmacokinetic-pharmacodynamic and toxicokinetic behavior that predict absorption and distribution. Likewise, these protocols must follow a theranostics approach, be able to detect promising formulations, diagnose the infectious disease, and determine the correct treatment to implement a personalized therapeutic behavior. Given the possibilities that nanotechnology offers, not updating to new screening platforms is inadequate as it prevents the correct application of discoveries, increasing the effect of the valley of death between innovations and their use. This book is structured to discuss the fundamentals taken into account for the design of robust, reproducible and automatable evaluation platforms. These vital platforms should enable the discovery of new medicines with which to face antimicrobial resistance (RAM), one of the great problems of our time.

Originally published in French, this updated and expanded English translation offers a definitive treatment on clays and effects on human health including the long history of clays used as pharmaceutical and therapeutic agents, the origins of clays, their structural properties and modes of action.

This book comprehensively reviews the state-of-the-art strategies developed for protein-protein interaction (PPI) inhibitors, and highlights the success stories in new drug discovery and development. Consisting of two parts with twelve chapters, it demonstrates the design strategies and case studies of small molecule PPI inhibitors. The first part discusses various discovery strategies for small molecule PPI inhibitors, such as high throughput screening, hot spot-based design, computational approaches, and fragment-based design. The second part presents recent advances in small molecule inhibitors, focusing on clinical candidates and new PPI targets. This book has broad appeal and is of significant interest to the pharmaceutical science and medicinal chemistry communities.

The book provides a reference for years to come, written by world-renowned expert investigators studying sex differences, the role of sex hormones, the systems biology of sex, and the genetic contribution of sex chromosomes to metabolic homeostasis and diseases. In this volume, leaders of the pharmaceutical industry present their views on sex-specific drug discovery. Many of the authors presented at the Keystone Symposium on "Sex and gender factors affecting metabolic homeostasis, diabetes and obesity" to be held in March 2017 in Lake Tahoe, CA. This book will generate new knowledge and ideas on the importance of gender biology and medicine from a molecular standpoint to the population level and to provide the methods to study them. It is intended to be a catalyst leading to gender-specific treatments of metabolic diseases. There are fundamental aspects of metabolic homeostasis that are regulated differently in males and females, and influence both the development of diabetes and obesity and the response to pharmacological intervention. Still, most preclinical researchers avoid studying female rodents due to the added complexity of research plans. The consequence is a generation of data that risks being relevant to only half of the population. This is a timely moment to publish a book on sex differences in diseases as NIH leadership has asked scientists to consider sex as a biological variable in preclinical research, to ensure that women get the same benefit of medical research as men.

Although the Bioequivalence (BE) requirements in many global jurisdictions have much in common, differences in certain approaches and requirements such as definitions and terms, choice of comparator (reference) product, acceptance criteria, fasted and fed studies, single and multi-dose studies, biowaivers and products not intended for absorption into the systemic circulation (locally acting medicines and dosage forms), amongst others, provide food for thought that standardisation should be a high priority objective in order to result in a harmonized international process for the market approval of products using BE. An important objective of Bioequivalence Requirements in Various Global Jurisdictions is to attempt to gather the various BE requirements used in different global jurisdictions to provide a single source of relevant information. This information from, Brazil, Canada, China, European Union, India, Japan, MENA, Russia South Africa, the USA and WHO will be of value to drug manufacturers, regulatory agencies, pharmaceutical scientists and related health organizations and governments around the world in the quest to harmonize regulatory requirements for the market approval of generic products.

This book examines statistical techniques that are critically important to Chemistry, Manufacturing, and Control (CMC) activities. Statistical methods are presented with a focus on applications unique to the CMC in the pharmaceutical industry. The target audience consists of statisticians and other scientists who are responsible for performing statistical analyses within a CMC environment. Basic statistical concepts are addressed in Chapter 2 followed by applications to specific topics related to development and manufacturing. The mathematical level assumes an elementary understanding of statistical methods. The ability to use Excel or statistical packages such as Minitab, JMP, SAS, or R will provide more value to the reader. The motivation for this book came from an American Association of Pharmaceutical Scientists (AAPS) short course on statistical methods applied to CMC applications presented by four of the authors. One of the course participants asked us for a good reference book, and the only book recommended was written over 20 years ago by Chow and Liu (1995). We agreed that a more recent book would serve a need in our industry. Since we began this project, an edited book has been published on the same topic by Zhang (2016). The chapters in Zhang discuss statistical methods for CMC as well as drug discovery and nonclinical development. We believe our book complements Zhang by providing more detailed statistical analyses and examples.

This book, the 5th volume in the Handbook of Analytical Separations series, gives an overview about methods to analyse drugs in biological fluids. The most widely used methods to analyse drugs in biological fluids. i.e. chromatographic methods, CE and immunoassays are described in detail. For important drugs, an overview about the methods available and a comparison of the techniques should be given to enable the reader to choose the right method depending on laboratory equipment, staff, the aim of the investigation etc. Other general aspects important for conducting therapeutic drug monitoring or pharmacokinetics studies are also covered, i.e. sample preparation, validation of the analytical methods and pharmacokinetic methods for interpreting the data. Areas where therapeutic drug monitoring is used frequently such as antibiotics, immunosuppressant drugs, antipsychotic and anticancer drugs will be discussed in detail. In addition, the important field of phenotyping and genotyping for therapy optimisation with special focus on real-life applications is also covered.
The book contains important information for analyst working on drug analysis in clinical chemistry, hospital pharmacists involved in therapeutic drug monitoring, other pharmacists, chemists or physicians working on pharmacokinetic studies in industry or academia.
In contrast to other books in this field, this book provides up-to-date information regarding both methodology and clinical applications. For the applications, only fields are described where therapeutic drug monitoring is used in clinical routine and provides benefit to the patients.
1. Overview of all important field where therapeutic drug monitoring is applied
2. All relevant analytical and computational methods are discussed
3. Written by experts with a lot of practical experience in the field

Founded in 1959, the series has moved from its initial focus on medicinal chemistry to a much wider scope. This volume encompasses all fields concerned with the development of therapeutic drugs, and the elucidation of their mechanisms of action. When combined with the other volumes, it serves as a time-saving source of information for researchers concerned with drug research, and all those who need to keep abreast of ongoing developments in medicines.

This volume provides an overview of the biochemical characterization, structure-function studies, proteomics, bioinformatics, molecular biology, transcriptomics and genomics of various spider species. The book also covers our current knowledge of venom components, toxins and their modes of action. The first section of Spider Venom includes contributions regarding the wide diversity of spider venom components and depicts some of their biological effects (antimicrobial, ion channel modulators, insecticides, this includes peptide and non-peptide toxins), and emphasizes spiders of public health importance. The second section covers transcriptomes, proteomes (and peptidomics), bioinformatics and molecular dynamics. The last section describes antimicrobial, insecticidal toxins, envenomation and the medical potential of spider venoms. Spider venoms are a great and extensive source of bioactive compounds, and as such form a boundless and bountiful area awaiting discovery. It is by virtue of dedicated scientists that new toxins are discovered and that new insights arise, leading the way towards the investigation of their pharmacological effects, and hopefully, as a consequence, arriving at the discovery of venom components as new drug candidates.

This volume offers a comprehensive guide on the theory and practice of amorphous solid dispersions (ASD) for handling challenges associated with poorly soluble drugs. In twenty-three inclusive chapters, the book examines thermodynamics and kinetics of the amorphous state and amorphous solid dispersions, ASD technologies, excipients for stabilizing amorphous solid dispersions such as polymers, and ASD manufacturing technologies, including spray drying, hot melt extrusion, fluid bed layering and solvent-controlled micro-precipitation technology (MBP). Each technology is illustrated by specific case studies. In addition, dedicated sections cover analytical tools and technologies for characterization of amorphous solid dispersions, the prediction of long-term stability, and the development of suitable dissolution methods and regulatory aspects. The book also highlights future technologies on the horizon, such as supercritical fluid processing, mesoporous silica, KinetiSol (R), and the use of non-salt-forming organic acids and amino acids for the stabilization of amorphous systems. Amorphous Solid Dispersions: Theory and Practice is a valuable reference to pharmaceutical scientists interested in developing bioavailable and therapeutically effective formulations of poorly soluble molecules in order to advance these technologies and develop better medicines for the future.

This six volume book set examines a range of topics and applications related to biotechnology. Volumes include fermentation and algal biotechnologies; agricultural biotechnology; medical biotechnology, biopharmaceutics; biosafety, bioethics, biotechnology policy; microbiomes; bioenergy and environmental biotechnology for sustainable development. The topics address significant aspects of the dairy and fermented foods; crop genetics, breeding and genomics; microalgae and novel products; molecular diagnostics and DNA forensics; biosafety, bioethics and legal issues in biotechnology; biotechnology policy advocacy, enlightenment and engagement with stakeholders; medical and pharmaceutical biotechnology; omics and bioinformatics; waste recycling, biofuels and environmental remediation; animal genetics, breeding and genomics; genetic resources conservation and utilization; medicinal and underutilized plants; medical insect biotechnology, genomics and molecular genetics of pests; microbiomes and microbial biotechnology; biotechnology education and curriculum development; and water and waste water research. Volumes include: I: Fermentation and Algal Biotechnologies for the Food, Beverage and other Bioproduct Industries II: Agricultural Biotechnology, Biodiversity and Bio-resources Conservation and Utilization III: Medical Biotechnology, Biopharmaceutics, Forensic Science and Bioinformatics IV: Biosafety and Bioethics in Biotechnology: Policy, Advocacy, and Capacity Building V: Microbiomes and Emerging Applications VI: Bioenergy and Environmental Biotechnology for Sustainable Development The book is a timely knowledge product that documents key issues on advances in biotechnology for use by a variety of readers including postgraduate students, professionals in the field, policy makers, science advocacy groups.