A significant improvement in the safety of modern vaccines has been the development of subunit vaccines, as these are composed of very well-defined and highly pure components, often recombinant proteins. However, since protein-based antigens in general are weakly immunogenic by themselves, co-administration of adjuvants is required to induce potent and persistent specific immune responses. In recent years, there has been substantial progress in the discovery of new efficient adjuvants for subunit vaccines that are often classified into delivery systems and immunopotentiating compounds that constitute pathogen-associated molecular patterns, such as the toll-like receptor ligands. The combination of delivery systems and immunopotentiators has appeared to represent extraordinarily good adjuvants due to concomitant enhanced antigen delivery and potent stimulation of innate immunity. Many of these adjuvants are of a particulate nature and mimic the structure and/or composition of microbes in a reductionist fashion. Examples are liposomes, polymeric nanoparticles, emulsions and virus-like particles. However, there are a substantial number of pharmaceutical challenges associated with the subunit vaccine development process due to the complex nature of the antigen-adjuvant combinations. These challenges will be presented and discussed in this book. The objective of the book is to compile the concepts essential for the understanding of the pharmaceutical science and technology associated with the delivery of subunit vaccines. The books goal is to provide a comprehensive overview of the scientific and regulatory challenges facing scientists who research and develop subunit vaccines. The scope of the book is wide. It is written in a manner that will enlighten newcomers to the field (e.g., PhD students or experienced scientist switching fields) yet provide an in-depth knowledge that would benefit a skilled worker in the field. "

In the next couple of years the human genome will be fully sequenced. This will provide us with the sequence and overall function of all human genes as well as the complete genome for many micro-organisms. Subsequently it is hoped, by means of powerful bioinformatic tools, to determine the gene variants that contribute to various multifactorial diseases and genes that exist in certain infectious agents but not humans. As a consequence, this will allow us to define the most appropriate levels for drug intervention. It can be expected that the number of potential drug targets will increase, possibly by a factor of 10 or more. Nevertheless, sequencing the human genome or, for that matter, the genome of other species will only be the starting point for the understanding of their biological function. Structural genomics is a likely follow-up, combined with new techniques to validate the therapeutic relevance of such newly discovered targets. Accordingly, it can be expected that in the near future we will witness a substantial increase in novel putative targets for drugs. To address these new targets effectively, we require new approaches and innovative tools. At present, two alternative, yet complementary, techniques are employed: experimental high-throughput screening (HTS) of large compound libraries, increasingly provided by combinatorial chemistry, and computational methods for virtual screening and de novo design. As kind of status report on the maturity of virtual screening as a technique in drug design, the first workshop on new approaches in drug design and discovery was held in March 1999, at Schloss Rauischholzhausen, near Marburg in Germany. More than 80 scientists gathered and discussed their experience with the different techniques. The speakers were invited to summarize their contributions together with their impressions on the present applicability of their approach. Several of the speakers followed this request which is summarized in this publication."

Interconnecting the fundamentals of supercritical fluid (SCF) technologies, their current and anticipated utility in drug delivery, and process engineering advances from related methodological domains and pharmaceutical applications, this volume unlocks the potential of supercritical fluids to further the development of improved pharmaceutical products-from drug powders for respiratory delivery to drug delivery systems for controlled release.

This volume explores the application of Quality by Design (QbD) to biopharmaceutical drug product development. Twenty-eight comprehensive chapters cover dosage forms, liquid and lyophilized drug products. The introductory chapters of this book define key elements of QbD and examine how these elements are integrated into drug product development. These chapters also discuss lessons learned from the FDA Office of Biotechnology Products pilot program. Following chapters demonstrate how QbD is used for formulation development ranging from screening of formulations to developability assessment to development of lyophilized and liquid formats. The next few chapters study the use of small-scale and surrogate models as well as QbD application to drug product processes such as drug substance freezing and thawing, mixing, sterile filtration, filling, lyophilization, inspection and shipping and handling. Later chapters describe more specialized applications of QbD in the drug product realm. This includes the use of QbD in primary containers, devices and combination product development. The volume also explores QbD applied to vaccine development, automation, mathematical modeling and monitoring, and controlling processes and defining control strategies. It concludes with a discussion on the application of QbD to drug product technology transfer as well as overall regulatory considerations and lifecycle management. Quality by Design for Biopharmaceutical Drug Product Development is an authoritative resource for scientists and researchers interested in expanding their knowledge on QbD principles and uses in creating better drugs.

Interest in chemical entities capable of blocking or modifying cell metabolism ultimately goes back to the discovery of the structure of DNA in the 1950s. Understanding of the biochemical processes involved in cell metabolism rapidly led to the idea that compounds could be designed which might interfere with these processes, and thus could be used in the treatment of the diseases caused by viral infection. Since then, several classes of drugs have been discovered which depend for their effect on modification of the proper functioning of nucleic acids and, with the introduction of acyclovir for the treatment of Herpes infections, nucleoside analogues have become the cornerstone of antiviral chemotherapy. The success of the early nucleoside agents, the toxicity and metabolic instability of many nucleoside analogues, and the effects of viral pathogens on public health are driving the design, synthesis and evaluation of new nucleoside analogues, with much attention turning to nucleosides containing non natural' sugar analogues. This book focuses on the development of these agents, and draws together all the available material in an easily consulted form, which at the same time guides the reader into the research literature on the subject. Written primarily for the medicinal chemist, coverage includes both synthetic strategies and outline guidance on the main trends in biological activity. Particular attention is drawn to the comparison of synthetic routes to compounds with their natural analogues. Finally, the important antiviral activities of the compounds are treated, including anti-retrovirus, anti-hepadnavirus and anti-herpes virus properties. Written mainly for medicinal chemists inthe pharmaceutical industry and synthetic organic chemists in academe, this book will also be attractive to researchers in institutions focusing on cellular metabolism. Advanced students of organic chemistry will find the clear discussion of the synthetic strategies adopted in the development of these compounds a useful introduction to this exciting and challenging area.

Nearly three thousand papers and patents are dedicated to the actual or potential uses of cyclodextrins in pharmacy and pharmaceutical formulations. This is the first book written for pharmacists and pharmaceutical technologists which not only critically summarizes the enormous amount of literature available, but which can be used as a handbook when looking for solutions to practical problems. The fundamentals -- chemistry of cyclodextrins and their derivatives -- their physical and chemical properties are condensed to the most relevant items in Chapters 1 and 2. Chapter 3 deals with the adsorption, metabolism and toxicological properties of cyclodextrins. Chapter 4 explains the formulation, structure, composition and advantageous effects of the cyclodextrin inclusion complexes. Chapter 5 describes the methods for preparation and characterization of drug/cyclodextrin complexes. Chapters 6 and 7 are dedicated to the pharmacokinetics, biopharmaceutical and technological aspects of drug/CD complexes. Chapter 8 treats the application and effects of cyclodextrins in various drug formulations. The Appendix comprises a collection of recipes for any type of drug formulation. This book is aimed at those who use cyclodextrins in drug formulations, to improve the properties of existing drug formulations, or who want to prepare quite new formulations.

Advanced Porous Biomaterials for Drug Delivery Applications probes cutting-edge progress in the application of advanced porous biomaterials in drug delivery fields. These biomaterials offer promise in improving upon the design, cost, and creation of potent novel drug delivery systems. The book focuses on two categories: nature engineered and synthetic advanced porous biomaterials, with a wide range of low-cost porous biomaterial-based systems that have been used for the delivery of diverse drugs through in vitro/in vivo approaches. Details how advanced porous biomaterial-assisted systems improve essential properties in drug delivery applications Explains how advanced porous biomaterials systems are being used and explored to improve overall performances of drug delivery systems in mitigating a variety of diseases Emphasizes major applications in drug delivery such as controlled release, cancer therapy, and targeted delivery, and with focus on oral, topical, and transdermal applications Focuses on both naturally available and synthetic low-cost advanced porous biomaterials and their role in enhancing important parameters in drug delivery applications Accessible to readers with bio and non-bio backgrounds This book is an ideal reference for academics, researchers, and industry professionals in the interdisciplinary fields of biomedicine and biomedical engineering, pharmaceuticals, materials science, and chemistry.

The first book in the newly created book series, Computer-Aided Drug Discovery and Design, focuses on the computational aspects of early drug discovery, drug target identification, and validation. It revises current classical paradigms in target and phenotypic-based drug design with still ingrained approximations and concepts and discusses the research in the new network approach concept that include kinetic selectivity and metabolic analysis. Many often-overlooked approximations and concepts in drug discovery are fully covered. Drug Target Selection and Validation includes both introductory sections and research-based sections to be of use to both students and research scientists in drug discovery, design, kinetics and metabolic analysis. Pharmaceutical scientists, pharmaceutics, drug developers, pharmacologists, biomedical researchers in computer science, medicinal chemists, and precision medicine developers benefit from the information provided. The book concludes with a chapter on chemical and structural databases.

Cosmetics are the most widely applied products to the skin and include creams, lotions, gels and sprays. Their formulation, design and manufacturing ranges from large cosmetic houses to small private companies. This book covers the current science in the formulations of cosmetics applied to the skin. It includes basic formulation, skin science, advanced formulation, and cosmetic product development, including both descriptive and mechanistic content with an emphasis on practical aspects. Key Features: Covers cosmetic products/formulation from theory to practice Includes case studies to illustrate real-life formulation development and problem solving Offers a practical, user-friendly approach, relying on the work of recognized experts in the field Provides insights into the future directions in cosmetic product development Presents basic formulation, skin science, advanced formulation and cosmetic product development

Validation of computer systems is the process that assures the formal assessment and report of quality and performance measures for all the life-cycle stages of software and system development, its implementation, qualification and acceptance, operation, modification, requalification, maintenance and retirement (PICS CSV PI 011-3). It is a process that demonstrates the compliance of computer systems functional and non-functional requirements, data integrity, regulated company procedures and safety requirements, industry standards, and applicable regulatory authority's requirements. Compliance is a state of being in adherence to application-related standards or conventions or regulations in laws and similar prescriptions. This book, which is relevant to the pharmaceutical and medical devices regulated operations, provides practical information to assist in the computer validation to production systems, while highlighting and efficiently integrating worldwide regulation into the subject. A practical approach is presented to increase efficiency and to ensure that the validation of computer systems is correctly achieved.

This handbook is unique in its comprehensive coverage of the subject and focus on practical applications in diverse fields. It includes methods for sample preparation, the role of certified reference materials, calibration methods and statistical evaluation of the results. Problems concerning inorganic and bioinorganic speciation analysis, as well as special aspects such as trace analysis of noble metals, radionuclides and volatile organic compounds are also discussed. A significant part of the content presents applications of methods and procedures in medicine (metabolomics and therapeutic drug monitoring); pharmacy (the analysis of contaminants in drugs); studies of environmental samples; food samples and forensic analytics - essential examples that will also facilitate problem solving in related areas.

This book review series presents current trends in modern biotechnology. The aim is to cover all aspects of this interdisciplinary technology where knowledge, methods and expertise are required from chemistry, biochemistry, microbiology, genetics, chemical engineering and computer science. Volumes are organized topically and provide a comprehensive discussion of developments in the respective field over the past 3-5 years. The series also discusses new discoveries and applications. Special volumes are dedicated to selected topics which focus on new biotechnological products and new processes for their synthesis and purification. In general, special volumes are edited by well-known guest editors. The series editor and publisher will however always be pleased to receive suggestions and supplementary information. Manuscripts are accepted in English.

This comprehensive volume discusses approaches for a systematic selection of delivery systems for various classes of therapeutic agents including small molecule, protein, and nucleic acid drugs.

Specific topics covered in this book include: Solution, suspension, gel, nanoparticle, microparticle, and implant dosage formsRefillable and microneedle devicesIntravitreal, suprachoroidal, intrascleral, transscleral, systemic, and topical routes of deliveryPhysical methods including iontophoresis for drug deliveryRational selection of routes of administration and delivery systemsNoninvasive and continuous drug monitoring Regulatory path to drug product developmentClinical endpoints for drug product developmentEmerging and existing drugs and drug targets

"Drug Product Development for the Back of the Eye" is authored by renowned ocular drug delivery experts, representing academic, clinical, and industrial organizations and serves as indispensable resource for ophthalmic researchers, drug formulation scientists, drug delivery and drug disposition scientists, as well as clinicians involved in designing and developing novel therapeutics for the back of the eye diseases. This book is also relevant for students in various disciplines including ophthalmology, pharmaceutical sciences, drug delivery, and biomedical engineering. Refillable and microneedle devicesIntravitreal, suprachoroidal, intrascleral, transscleral, systemic, and topical routes of deliveryPhysical methods including iontophoresis for drug deliveryRational selection of routes of administration and delivery systemsNoninvasive and continuous drug monitoring Regulatory path to drug product developmentClinical endpoints for drug product developmentEmerging and existing drugs and drug targets

"Drug Product Development for the Back of the Eye" is authored by renowned ocular drug delivery experts, representing academic, clinical, and industrial organizations and serves as indispensable resource for ophthalmic researchers, drug formulation scientists, drug delivery and drug disposition scientists, as well as clinicians involved in designing and developing novel therapeutics for the back of the eye diseases. This book is also relevant for students in various disciplines including ophthalmology, pharmaceutical sciences, drug delivery, and biomedical engineering. Refillable and microneedle devicesIntravitreal, suprachoroidal, intrascleral, transscleral, systemic, and topical routes of deliveryPhysical methods including iontophoresis for drug deliveryRational selection of routes of administration and delivery systemsNoninvasive and continuous drug monitoring Regulatory path to drug product developmentClinical endpoints for drug product developmentEmerging and existing drugs and drug targets

"Drug Product Development for the Back of the Eye" is authored by renowned ocular drug delivery experts, representing academic, clinical, and industrial organizations and serves as indispensable resource for ophthalmic researchers, drug formulation scientists, drug delivery and drug disposition scientists, as well as clinicians involved in designing and developing novel therapeutics for the back of the eye diseases. This book is also relevant for students in various disciplines including ophthalmology, pharmaceutical sciences, drug delivery, and biomedical engineering. "

The marine environment has been, and continues to be, a fruitful source of novel chemical compounds that are not found in terrestrial and freshwater organisms. Many of these substances show potential biomedical applications, which could lead to development of new pharmaceutical products. Research on the utilization of natural products from marine organisms is growing by leaps and bounds; one important reason why being that, investigators, through new diving technologies, are becoming able to explore at greater depths. Studies of these marine natural products include investigations of neuronal membrane-active toxins, ion channel blockers, antitumor and antiviral agents, and anti-inflammatory molecules. This volume is the sixth in the ongoing series.

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.

Progress in Drug Research is a prestigious book series (founded in 1959) which provides extensive expert-written reviews on a wide spectrum of highly topical areas in current pharmaceutical and pharmalogical research. Each volume contains fully cross-referencing indexes which link the volumes 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.

Volume 50 in the series includes:

P.N. Kaul: Drug discovery: Past, present and future

M. Rohmer: Isoprenoid biosynthesis via the mevalonate -- independent route, a novel target for antibacterial drugs

G. Edwards and A.H. Weston: Endothelium, -derived hyperpolarizing factor -- a critical appraisal

R.W. Rockhold: Glutamatic involvement in psychomotor stimulant action

J.M. Colacino and K.A. Staschke: The identification and development of antiviral agents for the treatment of chronic hepatitis B virus infection

T.D. Johnson: Polyamines and cerebral ischemia

The first contribution reviews the occurrence of xanthine alkaloids in the plant kingdom and the elucidation of the caffeine biosynthesis pathway, providing details of the N-methyltransferases, belonging to the motif B' methyltransferase family which catalyze three steps in the four step pathway leading from xanthosine to caffeine. The second contribution in this book provides a background on the molecule and related compounds and update knowledge on the most recent advances in Iboga alkaloids. The third contribution presents a comprehensive analysis of frequently occurring errors with respect to 13C NMR spectroscopic data and proposes a straightforward protocol to eliminate a high percentage of the most obvious errors.

Examples from various organs and diseases illustrate the potential benefit obtained when both therapeutic approaches are combined with delivery strategies. Representing the combined effort of several leading international research and clinical experts, this book, Emerging Trends in Cell and Gene Therapy, provides a complete account on and brings into sharp focus current trends and state-of-the-art in important areas at the interface of cell- and gene-based therapies. This book addresses the current fragmented understanding regarding these two research areas and fills the vast unmet educational need and interest of both students and researchers in academia and industry. Main features of the book: * Biological aspects of stem cell sources, differentiation and engineering. * Application of microfluidics to study stem cell dynamics * Potential clinical application of stem cells and gene therapy to specific human disease. * Utilization of biomaterials and stem cells in regenerative medicine with particular emphasis on spinal cord repair, ligament and bone tissue engineering. * Biomimetic multiscale topography for cell alignment.

Valuation is a hot topic among life sciences professionals. There is no clear understanding on how to use the different valuation approaches and how to determine input parameters. Some do not value at all, arguing that it is not possible to get realistic and objective numbers out of it. Some claim it to be an art. In the following chapters we will provide the user with a concise val- tion manual, providing transparency and practical insight for all dealing with valuation in life sciences: project and portfolio managers, licensing executives, business developers, technology transfer managers, entrep- neurs, investors, and analysts. The purpose of the book is to explain how to apply discounted cash flow and real options valuation to life sciences p- jects, i.e. to license contracts, patents, and firms. We explain the fun- mentals and the pitfalls with case studies so that the reader is capable of performing the valuations on his own and repeat the theory in the exercises and case studies. The book is structured in five parts: In the first part, the introduction, we discuss the role of the players in the life sciences industry and their p- ticular interests. We describe why valuation is important to them, where they need it, and the current problems to it. The second part deals with the input parameters required for valuation in life sciences, i.e. success rates, costs, peak sales, and timelines.

The Handbook of Pharmaceutical Controlled Release Technology reviews the design, fabrication, methodology, administration, and classifications of various drug delivery systems, including matrices, and membrane controlled reservoir, bioerodible, and pendant chain systems. Contains cutting-edge research on the controlled delivery of biomolecules! Discussing the advantages and limitations of controlled release systems, the Handbook of Pharmaceutical Controlled Release Technology -covers oral, transdermal, parenteral, and implantable delivery of drugs -discusses modification methods to achieve desired release kinetics -highlights constraints of system design for practical clinical application -analyzes diffusion equations and mathematical modeling -considers environmental acceptance and tissue compatibility of biopolymeric systems for biologically active agents -evaluates polymers as drug delivery carriers -describes peptide, protein, micro-, and nanoparticulate release systems -examines the cost, comfort, disease control, side effects, and patient compliance of numerous delivery systems and devices -and more!

This book illustrates the importance of the Natural Biometabolites, which offer a rich reservoir of candidate compounds for drug discovery in the battle against cancer. Recent research and development efforts concerning anti-cancer drugs derived from natural products have led to the identification of numerous candidate molecules that inhibit cancer cell proliferation and metastasis using a variety of mechanisms. Given its scope, the book offers a valuable resource for cancer biologists and general oncologists alike, while also benefitting research professionals in Science, Nursing, Medicine, Biochemistry, Genetics and Bioscience who wish to understand the fundamentals of prognosis and prediction in tumorigenesis. Moreover, the book provides an essential platform for understanding drug resistance mechanisms and combatting the growing menace of multidrug resistance.

A reference is needed that addresses the recent progress in aspects of PK/PD methods and developments of nanoparticles for novel drug delivery systems. No other consolidated published reference discusses the PK/PD study of nanoparticle drug delivery systems. This book discusses the advantages of nanoparticle drug delivery systems (NPDDS) in enhancing the pharmacokinetics of many drugs that are not easily metabolized or that obtain the desired therapeutic effect with minimum toxicity. The authors provide an overview of biodistribution with a focus on polymer and lipid nanoparticles. This thorough reference is divided into three parts: Modelling, Specific carries and their potential to treat specific diseases.

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 will focus on the secondary metabolic compounds which afford protection against diseases. Lastly, Volume 3 focuses on 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.

Pharmaceutical product development is a multidisciplinary activity involving extensive efforts in systematic product development and optimization in compliance with regulatory authorities to ensure the quality, efficacy and safety of resulting products. Pharmaceutical Product Development equips the pharmaceutical formulation scientist with extensive and up-to-date knowledge of drug product development and covers all steps from the beginning of product conception to the final packaged form that enters the market and lifecycle management thereof. Applications of core scientific principles for product development are also thoroughly discussed in conjunction with the latest approaches involving design of experiment and quality by design with comprehensive illustrations based on practical case studies of several dosage forms. The book presents pharmaceutical product development information in an easy-to-read mode with simplified theories, case studies and guidelines for students, academicians and professionals in the pharmaceutical industry. It is an invaluable resource and hands-on guide covering managerial, regulatory and practical aspects of pharmaceutical product lifecycle management.

Authored by leading experts from academia, users and manufacturers, this book provides an authoritative account of the science and technology involved in multiparticulate drug delivery systems which offer superior clinical and technical advantages over many other specialized approaches in drug delivery. The book will cover market trends, potential benefits and formulation challenges for various types of multiparticulate systems. Drug solubility, dose, chemistry and therapeutic indications as well as excipient suitability coupled with manufacturing methods will be fully covered. Key approaches for taste-masking, delayed release and extended release of multiparticulates systems are of significant interest, especially their in-vivo and in-vitro performance. In addition, the principles of scale-up, QbD, and regulatory aspects of common materials used in this technology will be explained, as well as recent advances in materials and equipment enabling robust, flexible and cost-effective manufacture. Case studies illustrating best practices will also make the book a valuable resource to pharmaceutical scientists in industry and academia.