Proteins are exposed to various interfacial stresses during drug product development. They are subjected to air-liquid, liquid-solid, and, sometimes, liquid-liquid interfaces throughout the development cycle-from manufacturing of drug substances to storage and drug delivery. Unlike small molecule drugs, proteins are typically unstable at interfaces where, on adsorption, they often denature and form aggregates, resulting in loss of efficacy and potential immunogenicity. This book covers both the fundamental aspects of proteins at interfaces and the quantification of interfacial behaviors of proteins. Importantly, this book introduces the industrial aspects of protein instabilities at interfaces, including the processes that introduce new interfaces, evaluation of interfacial instabilities, and mitigation strategies. The audience that this book targets encompasses scientists in the pharmaceutical and biotech industry, as well as faculty and students from academia in the surface science, pharmaceutical, and medicinal chemistry areas.

This book offers an overview of the statistical methods used in clinical and observational vaccine studies. Pursuing a practical rather than theoretical approach, it presents a range of real-world examples with SAS codes, making the application of the methods straightforward. This revised edition has been significantly expanded to reflect the current interest in this area. It opens with two introductory chapters on the immunology of vaccines to provide readers with the necessary background knowledge. It then continues with an in-depth exploration of the analysis of immunogenicity data. Discussed are, amongst others, maximum likelihood estimation for censored antibody titers, ANCOVA for antibody values, analysis of data of equivalence, and non-inferiority immunogenicity studies. Other topics covered include fitting protection curves to data from vaccine efficacy studies, and the analysis of vaccine safety data. In addition, the book features four new chapters on vaccine field studies: an introductory one, one on randomized vaccine efficacy studies, one on observational vaccine effectiveness studies, and one on the meta-analysis of vaccine efficacy studies. The book offers useful insights for statisticians and epidemiologists working in the pharmaceutical industry or at vaccines institutes, as well as graduate students interested in pharmaceutical statistics.

Non-linear phenomena pervade the pharmaceutical sciences. Understanding the interface between each of these phenomena and the way in which they contribute to overarching processes such as pharmaceutical product development may ultimately result in more efficient, less costly and rapid implementation. The benefit to Society is self-evident in that affordable treatments would be rapidly forthcoming. We have aggregated these phenomena into one topic "Pharmaco-complexity: Non-linear Phenomena and Drug Product Development".

This is an introductory statistics book designed to provide scientists with practical information needed to apply the most common statistical tests to laboratory research data. The book is designed to be practical and applicable, so only minimal information is devoted to theory or equations. Emphasis is placed on the underlying principles for effective data analysis and survey the statistical tests. It is of special value for scientists who have access to Minitab software. Examples are provides for all the statistical tests and explanation of the interpretation of these results presented with Minitab (similar to results for any common software package). The book is specifically designed to contribute to the AAPS series on advances in the pharmaceutical sciences. It benefits professional scientists or graduate students who have not had a formal statistics class, who had bad experiences in such classes, or who just fear/don't understand statistics. Chapter 1 focuses on terminology and essential elements of statistical testing. Statistics is often complicated by synonyms and this chapter established the terms used in the book and how rudiments interact to create statistical tests. Chapter 2 discussed descriptive statistics that are used to organize and summarize sample results. Chapter 3 discussed basic assumptions of probability, characteristics of a normal distribution, alternative approaches for non-normal distributions and introduces the topic of making inferences about a larger population based on a small sample from that population. Chapter 4 discussed hypothesis testing where computer output is interpreted and decisions are made regarding statistical significance. This chapter also deasl with the determination of appropriate sample sizes. The next three chapters focus on tests that make decisions about a population base on a small subset of information. Chapter 5 looks at statistical tests that evaluate where a significant difference exists. In Chapter 6 the tests try to determine the extent and importance of relationships. In contrast to fifth chapter, Chapter 7 presents tests that evaluate the equivalence, not the difference between levels being tested. The last chapter deals with potential outlier or aberrant values and how to statistically determine if they should be removed from the sample data. Each statistical test presented includes an example problem with the resultant software output and how to interpret the results. Minimal time is spent on the mathematical calculations or theory. For those interested in the associated equations, supplemental figures are presented for each test with respective formulas. In addition, Appendix D presents the equations and proof for every output result for the various examples. Examples and results from the appropriate statistical results are displayed using Minitab 18O. In addition to the results, the required steps to analyze data using Minitab are presented with the examples for those having access to this software. Numerous other software packages are available, including based data analysis with Excel.

The first contribution summarizes current trends in research on medicinal plants in Mexico with emphasis on work carried out at the authors' laboratories. The most relevant phytochemical and pharmacological profiles of a selected group of plants used widely for treating major national health problems are described. The second contribution provides a detailed survey of the so far reported literature data on the capacities of selected oxyprenylated phenylpropanoids and polyketides to trigger receptors, enzymes, and other types of cellular factors for which they exhibit a high degree of affinity and therefore evoke specifice responses. And the third contribution discusses aspects of endophytic actinobacterial biology and chemistry, including biosynthesis and total synthesis of secondary metabolites produced in culture. It also presents perspectives fo the future of microbial biodiscovery, with emphasis on the seondary metabolism of endophytic actinobacteria.

This work presents a comprehensive contemporary framework for approaching target validation in drug discovery. It begins with a detailed description of new enabling technologies, including aptamers, RNA interference, functional genomics, and proteomics. The next section looks at biologic drug development with in-depth discussion of lessons learned from such well-known cases as Erbitux, Herceptin, and Avastin. Additional targets known as "second generation" drugs, which can be identified when disease pathways are validated by biologics, present new possible small molecule therapeutics and serve as the focus of the final section of the book.

This book compiles the fundamentals, applications and viable product strategies of biomimetic lipid membranes into a single, comprehensive source. It broadens its perspective to interdisciplinary realms incorporating medicine, biology, physics, chemistry, materials science, as well as engineering and pharmacy at large. The book guides readers from membrane structure and models to biophysical chemistry and functionalization of membrane surfaces. It then takes the reader through a myriad of surface-sensitive techniques before delving into cutting-edge applications that could help inspire new research directions. With more than half the world's drugs and various toxins targeting these crucial structures, the book addresses a topic of major importance in the field of medicine, particularly biosensor design, diagnostic tool development, vaccine formulation, micro/nano-array systems, and drug screening/development. Provides fundamental knowledge on biomimetic lipid membranes; Addresses some of biomimetic membrane types, preparation methods, properties and characterization techniques; Explains state-of-art technological developments that incorporate microfluidic systems, array technologies, lab-on-a-chip-tools, biosensing, and bioprinting techniques; Describes the integration of biomimetic membranes with current top-notch tools and platforms; Examines applications in medicine, pharmaceutical industry, and environmental monitoring.

This second edition of Clinical Use of Anti-Infective Agents provides a comprehensive overview of current approaches to using drugs to treat infections, including historical perspectives, definitions, and discussion of pharmacokinetics and pharmacodynamics and their uses. It includes a detailed explanation of different classes of drugs, outlining their spectrum, pharmacokinetics, side effects, and dosing in clinical settings. This book has been designed as a reference tool for pharmacists, clinicians, nurse practitioners, and clinical microbiologists, as well as a teaching vehicle for students studying infection and patient treatment. Each section includes references allowing for in-depth study of specific agents, Q&As, and illustrative case studies accompanied by commentary on how to approach patients and organisms, optimal methods of making a diagnosis, and prescribing treatment.

This book introduces readers to the latest advances in G protein-coupled receptor (GPCR) biology. It reviews our current understanding of the structural basis of ligand binding and allosteric mechanisms, following a decade of technological breakthroughs. Several examples of structure-based drug discovery are presented, together with the future challenges involved in designing better drugs that target GPCRs. In turn, the book illustrates the important concept of GPCR biased signaling in physiological contexts, and presents fluorescent- and light-based methodologies frequently used to measure GPCR signaling or to trace their dynamics in cells upon ligand activation. Taken together, the chapters provide an essential overview and toolkit for new scientific investigators who plan to develop GPCR projects. All chapters were written by experts in their respective fields, and share valuable insights and powerful methodologies for the GPCR field.

Early anthropological evidence for plant use as medicine is 60,000 years old as reported from the Neanderthal grave in Iraq. The importance of plants as medicine is further supported by archeological evidence from Asia and the Middle East. Today, around 1.4 billion people in South Asia alone have no access to modern health care, and rely instead on traditional medicine to alleviate various symptoms. On a global basis, approximately 50 to 80 thousand plant species are used either natively or as pharmaceutical derivatives for life-threatening conditions that include diabetes, hypertension and cancers. As the demand for plant-based medicine rises, there is an unmet need to investigate the quality, safety and efficacy of these herbals by the "scientific methods". Current research on drug discovery from medicinal plants involves a multifaceted approach combining botanical, phytochemical, analytical, and molecular techniques. For instance, high throughput robotic screens have been developed by industry; it is now possible to carry out 50,000 tests per day in the search for compounds, which act on a key enzyme or a subset of receptors. This and other bioassays thus offer hope that one may eventually identify compounds for treating a variety of diseases or conditions. However, drug development from natural products is not without its problems. Frequent challenges encountered include the procurement of raw materials, the selection and implementation of appropriate high-throughput bioassays, and the scaling-up of preparative procedures. Research scientists should therefore arm themselves with the right tools and knowledge in order to harness the vast potentials of plant-based therapeutics. The main objective of Plant and Human Health is to serve as a comprehensive guide for this endeavor. Volume 1 highlights how humans from specific areas or cultures use indigenous plants. Despite technological developments, herbal drugs still occupy a preferential place in a majority of the population in the third world and have slowly taken roots as alternative medicine in the West. The integration of modern science with traditional uses of herbal drugs is important for our understanding of this ethnobotanical relationship. Volume 2 deals with the phytochemical and molecular characterization of herbal medicine. Specifically, it focuess on the secondary metabolic compounds, which afford protection against diseases. Lastly, Volume 3 discusses the physiological mechanisms by which the active ingredients of medicinal plants serve to improve human health. Together this three-volume collection intends to bridge the gap for herbalists, traditional and modern medical practitioners, and students and researchers in botany and horticulture.

Absorption, Distribution, Metabolism and Excretion (ADME) processes and their relationship with the design of dosage forms and the success of pharmacotherapy form the basis of this upper level undergraduate/graduate textbook. As an introduction oriented to pharmacy students, it is also written for scientist from different fields outside of pharmaceutics. (e.g. material scientist, material engineers, medicinal chemists) who might be working in a positions in pharmaceutical companies or whose work might benefit from basic training in the ADME concepts and some biological background. Pedagogical features such as objectives, keywords, discussion questions, summaries and case studies add valuable teaching tools. This book will provide not only general knowledge on ADME processes but also an updated insight on some hot topics such as drug transporters, multi-drug resistance related to pharmacokinetic phenomena, last generation pharmaceutical carriers (nanopharmaceuticals), in vitro and in vivo bioequivalence studies, biopharmaceuticals, pharmacogenomics, drug-drug and food-drug interactions, and in silico and in vitro prediction of ADME properties. In comparison with other similar textbooks, around half of the volume would be focused on the relationship between expanding scientific fields and ADME processes. Each of these burgeoning fields has a separate chapter in the second part of the volume, and was written with leading experts on the correspondent topic, including scientists and academics from USA and UK (Duquesne University School of Pharmacy, Indiana University School of Medicine, University of Utah College of Pharmacy, University of Maryland, University of Bath). Additionally, each of the initial chapters dealing with the generalities of drug absorption, distribution, metabolism and excretion would include relevant, classic examples related to each topic with appropriate illustrations (e.g. importance of active absorption of levodopa, implications in levodopa administration, drug drug interactions and food drug interactions emerging from the active uptake; intoxication with paracetamol as a result of glutathione depletion, CYP induction and its relationship with acute liver failure caused by paracetamol, etc). ADME Processes and Pharmaceutical Sciences is written as a core textbook for ADME processes, pharmacy, pharmacokinetics, drug delivery, biopharmaceutics, drug disposition, drug design and medicinal chemistry courses.

This third edition volume expands on the previous editions with new topics that cover drug discovery through translational bioinformatics, informatics, clinical research informatics, as well as clinical informatics. The chapters discuss new methods to study target identification, genome analysis, cheminformatics, protein analysis, and text mining. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials, software workflows, reagents and on-line resources, together with step-by-step, readily reproducible laboratory and computational protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Bioinformatics and Drug Discovery, Third Edition is a valuable resource for anyone interested in drug design, including academicians (biologists, informaticists and data scientists, chemists, and biochemists), clinicians, and pharmaceutical scientists.

Volume 22, entitled Metal Ions in Bio-Imaging Techniques, of the series Metal Ions in Life Sciences deals with metal ions as tools in imaging. This dates back to the first half of the past century, when barium sulfate was orally given to patients undergoing X-ray examination. The use of contrast agents has since developed into a large interdisciplinary field encompassing not only medicine, but also chemistry, material sciences, physics, biology, engineering, and computer sciences. MILS-22 provides deep and current insights in 17 stimulating chapters on the new research frontiers of this fast growing field on bio-imaging ... and beyond. For example, adding bio-sensing yields theranostic agents, meaning diagnosis and therapy linked in the same molecule; ions of Gd, Mn, Fe, Co, Ir, 99mTc, etc., are involved. Other important topics are, e.g., metal complexes in paramagnetic Chemical Exchange Transfer (paraCEST), radiometals for Positron Emission Tomography (PET) imaging, or paramagnetic metal ion probes for 19F magnetic resonance imaging. MILS-22 is written by 57 internationally recognized experts from 12 countries, that is, from the US via Europe to China. The impact of this vibrant research area is manifested by more than 2300 references and nearly 120 figures, mostly in color, and several informative tables. To conclude, Metal Ions in Bio-Imaging Techniques is an essential resource for scientists working in the wide range from material sciences, enzymology, analytic, organic, and inorganic biochemistry all the way through to medicine including the clinic ... not forgetting that also excellent information for teaching is provided.

Stimuli Responsive Polymeric Nanocarriers for Drug Delivery Applications, Volume One: Types and Triggers discusses, in detail, the recent trends in designing biodegradable and biocompatible single-responsive polymers and nanoparticles for safe drug delivery. Focusing on the most advanced materials and technologies, evaluation methods, and advanced synthesis techniques stimuli-responsive polymers, the book is an essential reference for scientists with an interest in drug delivery vehicles. Sections focus on innovation, development and the increased global demand for biodegradable and biocompatible responsive polymers and nanoparticles for safe drug delivery.

Fullerens, Graphenes and Nanotubes: A Pharmaceutical Approach shows how carbon nanomaterials are used in the pharmaceutical industry. While there are various books on the carbonaceous nanomaterials available on the market, none approach the subject from a pharmaceutical point-of-view. In this context, the book covers different applications of carbonaceous nanomaterials. Chapters examine different types of carbon nanomaterials and explore how they are used in such areas as cancer treatments, pulse sensing and prosthetics. Readers will find this book to be a valuable reference resource for those working in the areas of carbon materials, nanomaterials and pharmaceutical science.

Focusing on the application of nanotechnology in pharmaceutical technology the editors seek to integrate the two in order to obtain innovative products and solutions in pharmacology. Interdisciplinary in content it is of interest to those who are involved in the development of nanoproducts including nanotechnologists, microbiologists, biotechnologists pharmacologists and clinicians. Recent studies are presented that include the biosynthesis of nanoparticles focusing on antimicrobials; nanomaterial-based formulations that treat cancer, infections, skin disorders and wounds;nanomaterials in eye diseases and toxicity and safety issues. It demonstrates the crucial role this plays in tackling multi-drug resistant threats.

This book reviews the advances and challenges of structure-based drug design in the preclinical drug discovery process, addressing various diseases, including malaria, tuberculosis and cancer. Written by internationally recognized researchers, this edited book discusses how the application of the various in-silico techniques, such as molecular docking, virtual screening, pharmacophore modeling, molecular dynamics simulations, and residue interaction networks offers insights into pharmacologically active novel molecular entities. It presents a clear concept of the molecular mechanism of different drug targets and explores methods to help understand drug resistance. In addition, it includes chapters dedicated to natural-product- derived medicines, combinatorial drug discovery, the CryoEM technique for structure-based drug design and big data in drug discovery. The book offers an invaluable resource for graduate and postgraduate students, as well as for researchers in academic and industrial laboratories working in the areas of chemoinformatics, medicinal and pharmaceutical chemistry and pharmacoinformatics.

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.

This textbook provides a comprehensive overview of the currently used concepts, approaches and technologies in the discovery and development of new treatments for the full spectrum of disorders of the central nervous system. It guides the reader through all essential steps, from finding an innovative idea, to the registration of a new drug. Divided into four sections, the book starts by presenting a broad perspective on current approaches in central nervous system (CNS) drug discovery. The second section addresses the generation of ideas for the identification of targets and novel treatment strategies; covers core functions in early discovery, and provides an example of a novel treatment paradigm: brain stimulation. The third section highlights strategies and technologies in translational CNS drug discovery. In an effort to bridge the gap between discovery and clinical development, it also covers brain imaging, EEG and cognitive testing approaches. The fourth section extensively discusses the clinical phase of drug development, covering the basics of early clinical testing for psychopharmacological drugs. The book's final chapter addresses the registration for newly developed drugs. Written by experts from academia and industry, the book covers important basics and best practices, as well as recent developments in drug discovery. Offering in-depth insights into the world of drug development, it represents essential reading for early researchers who want to prepare for a career in drug discovery in academia or industry.

Natural Products and Drug Discovery: An Integrated Approach provides an applied overview of the field, from traditional medicinal targets, to cutting-edge molecular techniques. Natural products have always been of key importance to drug discovery, but as modern techniques and technologies have allowed researchers to identify, isolate, extract and synthesize their active compounds in new ways, they are once again coming to the forefront of drug discovery. Combining the potential of traditional medicine with the refinement of modern chemical technology, the use of natural products as the basis for drugs can help in the development of more environmentally sound, economical, and effective drug discovery processes. Natural Products & Drug Discovery: An Integrated Approach reflects on the current changes in this field, giving context to the current shift and using supportive case studies to highlight the challenges and successes faced by researchers in integrating traditional medicinal sources with modern chemical technologies. It therefore acts as a useful reference to medicinal chemists, phytochemists, biochemists, pharma R&D professionals, and drug discovery students and researchers.

Progress in Drug Research is a prestigious book series which provides extensive expert-written reviews on a wide spectrum of highly topical areas in current pharmaceutical and pharmacological research. Founded in 1959 by its current editor, the series has moved from its initial focus on medicinal chemistry to a much wider scope. Today it encompasses all fields concerned with the development of new therapeutic drugs and the elucidation of their mechanisms of action, reflecting the increasingly complex nature of modern drug research. Invited authors present their biological, chemical, biochemical, physiological, immunological, pharmaceutical, toxicological, pharmacological and clinical expertise in carefully written reviews and provide the newcomer and the specialist alike with an up-to-date comprehensive list of prime references. Each volume of Progress in Drug Research contains fully cross-referencing indices which link the books together, forming a virtually encyclopaedic work. The series thus serves as an important, time-saving source of information for researchers concerned with drug research and all those who need to keep abreast of the many recent developments in the quest for new and better medicines.

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.

Completely revised and updated, this third edition of Pharmaceutical Dosage Forms and Drug Delivery elucidates the basic principles of pharmaceutics, biopharmaceutics, dosage form design, and drug delivery - including emerging new biotechnology-based treatment modalities. The authors integrate aspects of physical pharmacy, chemistry, biology, and biopharmaceutics into drug delivery. This book highlights the increased attention that the recent spectacular advances in gene therapy and nanotechnology have brought to dosage form design and drug delivery. With the expiration of older patents and generic competition, the biopharmaceutical industry is evolving faster than ever. Apart from revising and updating existing chapters on the basic principles, this edition highlights the emerging emphasis on drug discovery, antibodies and antibody-drug conjugates as therapeutic moieties, individualized medicine including patient stratification strategies, targeted drug delivery, and the increasing role of modeling and simulation. Although there are numerous books on pharmaceutics and dosage forms, most cover different areas of the discipline and do not provide an integrated approach. The integrated approach of this book not only provides a singular perspective of the overall field, but also supplies a unified source of information for students, instructors and professionals, saving their time and money.

This book explores technological innovation in family firms, seeking to reconstruct the links between the heterogeneous dimensions of family businesses and their innovative behaviour. Building on and examining the traditional view of family firms as conservative, this book contributes to knowledge surrounding the puzzling role of family firms in technological innovation, with particular focus on the Italian pharmaceutical industry. The authors explore technological advances within the industry in connection with various features of family governance. This thought-provoking study is divided into two parts, the first part providing an overview of current literature on the topic, and the second part analysing the findings of empirical investigation in a specific industry setting. Practitioners and academics of business strategy will find this book extremely useful as it combines both solid theoretical reasoning and robust empirical analysis.