bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarkers: Facing the Challenges at the Crossroads of Research and Health Care
Authors: Downing Gregory J.
Published: March 2010

In recent years, across many segments of the biomedical research enterprise and the health care delivery sectors, the impact of biomarkers has been transforming in many ways: from business and economics to policy and planning of disease management. Clinical applications of biomarkers in medical practice are also coming more into focus through diagnostics and molecularly targeted therapies. This article discusses the medical research history that led to the shaping of new directions that is captured simply by the term biomarker, a biological indicator of health or disease.
Quantitative Multiplexed Patterning of Immune‐Related Biomarkers
Authors: Eisinger Dominic , McDade Ralph , Joos Thomas
Published: March 2010

Immune‐related biomarker patterning has great potential to improve the success rate of drug approval in a highly cost‐effective manner. The efficiency of simultaneous profiling of multiple immune‐related biomarkers with very small sample volumes has revolutionized our ability to discover and validate biomarker patterns in order to stratify patients and find markers of efficacy and safety. This article focuses on the multiplexed immunoassay measurement technologies as well as some recent and relevant examples of successful biomarker patterning.
Gene Expression Profiles as Preclinical and Clinical Cancer Biomarkers of Prognosis, Drug Response, and Drug Toxicity
Authors: Sprowl Jason A. , Parissenti Amadeo M.
Published: March 2010

Measurement of the expression level of specific genetic or protein biomarkers in patient serum or biopsies can be extremely valuable in the diagnosis and treatment of a variety of human neoplasms. However, tumor or serum level of large groups of proteins or transcripts is necessary to predict patient prognosis or outcome reliably after chemotherapy. This article focuses on the current progress made in the use of gene profiling to predict patient prognosis and response or toxicity to specific chemotherapy regimens.
Characterization and Validation Biomarkers in Drug Development: Regulatory Perspective
Authors: Goodsaid Federico
Published: March 2010

Novel approaches are being tested continuously for the successful integration of biomarkers in drug development. However, integration of these novel biomarkers into routine nonclinical and clinical practice, and regulatory submissions, have often been slow due to fear about how comprehensive data support these applications and regulatory interpretation of the context of use for these applications. This article focuses on the regulatory paths in biomarker evaluation and qualification, including ICH harmonization procedures.
Importance of Statistics in the Qualification and Application of Biomarkers
Authors: Zacour Mary
Published: March 2010

The field of biomarkers is a wide one, with a huge diversity of potential applications, all of which may have different and complex statistical analysis issues. Scientists need to consider potential data analysis issues before settling on experimental design. This article addresses data analysis issues pertinent to biomarker research in drug development.
New Markers of Kidney Injury
Authors: Beushausen Sven A.
Published: March 2010

The current biomarker standards for assessing acute kidney injury (AKI) include blood urea nitrogen (BUN) and serum creatinine (SC), which lack sensitivity and specificity for kidney injury. The combined shortcomings of BUN and SC aspredictorsof nephrotoxicity and the propensity for many classes of medicines to cause drug‐induced nephrotoxicity underscore the urgent need for the development and qualification of more sensitive and specific biomarkers. This article focuses on the importance of new biomarkers of nephrotoxicity in predicting and monitoring early or acute kidney injury.
Integrating Molecular Testing into Clinical Applications
Authors: Killeen Anthony A.
Published: March 2010

The clinical laboratory plays a critical role in modern health care. In the United States, the clinical laboratory operates under the regulations of the Clinical Laboratory Improvement Amendments of 1988, which provide the framework for producing high‐quality results. This article focuses on the principal issues surrounding the integration of molecular testing into the clinical laboratory environment.
Biomarkers in Pharmaceutical Development: The Essential Role of Project Management and Teamwork
Authors: King Lena , Jurima‐Romet Mallé , Ichhpurani Nita
Published: March 2010

The successful launch of a novel pharmaceutical product represents the culmination of years of discovery and development work driven by knowledgeable people passionate about their project and the pharmaceutical. The development process requires perseverance, and cannot be successful without coordination and teamwork. This article focuses on the role of project management and teamwork in development of pharmaceutical and consequences of employing novel biomarkers or a unique biomarker strategy in pharmaceutical development.
From Gene to Product: the Advantage of Integrative Biotechnology
Authors: Schmidt Frank‐Ranier
Published: March 2010

Biotechnology is gaining in increasing importance in pharmaceutical production processes by replacing chemical production procedures for economical and ecological reasons and in the development and commercialization of novel therapeutic principles. To fully exploit the potential of biotechnological production methods, an integrated process design will be necessary considering the downstream processing requirement during the design of upstream operations and vice versa. This chapter aims is to give insights into the typical issues and problems encountered in the manufacture of biopharmaceuticals, to mediate general ideas and current strategies on how to proceed in the design and development of biotechnological processes.
Overview: Differentiating Issues in the Development of Macromolecules Compared with Small Molecules
Authors: Blaich Günter , Janssen Bernd , Roth Gregory , Salfeld Jochen
Published: March 2010

The fundamental overall structural differences dictate unique approaches for discovery and development of small‐molecule and macromolecule drug. The overall drug discovery/development process can be divided into four convenient steps: target selection and validation; choice between small‐molecule and macromolecule platforms; definition of target product profile; and drug discovery and development. This article focuses on various issues associated with development of macromolecules compared small molecules.
Integrated Development of Glycobiologics: from Discovery to Applications in the Design of Nanoparticular Drug Delivery Systems
Authors: Vauthier Christine , Bertholon Isabelle , Labarre Denis
Published: March 2010

The interactions of nanoparticle drug carriers with the surrounded biological environment are key factors controlling the in vivo fate of the transported drugs. Three levels of interactions may be distinguished and all involve surface phenomena between nanoparticle surface and compounds of the surrounding environment. This article focuses on the main stages of the development of carbohydrates and polysaccharides as a targeted drug or as a component entering the design of drug delivery systems.
R&DParadigm Shift and Billion‐Dollar Biologics
Authors: Maggon Krishan
Published: March 2010

R&D success has been linked to the development and creation of billion‐dollar human medication. The blockbuster drugs are the main driver of industrial R&D and contribute a major share of the total pharmaceutical sales, profits, and market value of the successful companies. This article describes successes and failures of biotechnology R&D, criteria for blockbuster brands, global sales of biologics blockbuster brands, changing regulations, cost constraints, public‐private partnership to deliver and develop low‐cost treatments for tropical diseases, and information resources for biologics.
Basic Issues in the Manufacture of Macromolecules
Authors: Lengsfeld Corinne , Anchordoquy Thomas
Published: March 2010

The manufacturing methods for proteins and plasmid DNA require a cellular medium to either express a protein or replicate genetic material. Cell culture plays a large role in the efficiencies of macromolecular production as well as in the separation process. This article describes the initial manufacturing steps involved in the production of therapeutic proteins and plasmid DNA.
Protein Posttranslational Modification: A Potential Target in Pharmaceutical Development
Authors: Huq M.D. Mostaqul , Wei Li‐Na
Published: March 2010

Protein posttranslational modification (PTM) is a hallmark of signal transduction and it allows the cells to rapidly respond to extracellular signals. These modifications, which involve stable and sometimes irreversible additions of non‐amino acid to primary translation products, occur in a large proportion of the cellular protein pool. This article focuses on important issues in PTM studies, such as need for protein modification, how proteins are modified, and basic tools for studying PTM.
Pegylation: Camouflage of Proteins, Cells, and Nanoparticles Against Recognition by the Body's Defense Mechanism
Authors: Cho Yong Woo , Park Jae Hyung , Park Ji Sun , Park Kinam
Published: March 2010

Polyethylene glycol (PEG) is becoming a standard polymer for chemical modification of proteins and peptides to enhance their pharmaceutical properties. PEGylation is increasingly used for attaching PEG to various objects, such as peptides, proteins, cells and other biologically active materials. This article focuses on pegylation of proteins, which has brought numerous clinically useful products and triggered explosive interest in polymers in the field of pharmaceutical biotechnology.
Unexpected Benefits of a Formulation: Case Study with Erythropoetin
Authors: Keast David
Published: March 2010

Recombinant human erythropoietin (rHuEPO) is a purified glycoprotein produced by recombinant DNA technology. It has the capability for the treatment of the anemia associated with chronic renal failure and prematurity. This article provides an overview of human recombinant erythropoietin which significantly improves the quality of life for patients on real dialysis by managing the concomitant anemia.
Capillary Separation Techniques
Authors: Na Dong Hee , Lee Kang Choon
Published: March 2010

Capillary electrophoresis (CE) is being extensively applied for characterization of biotechnology derived products like peptides and proteins. Recently, the role of CE in the strategy of protein analysis increases, with an emphasis on multidimensional separation and the combination of mass spectrometric techniques. This article gives emphasis on the fundamental principles of CE and its application to the separation and characterization of peptides and proteins.
Analytical Considerations for Immunoassays for Macromolecules
Authors: Kelley Marian , DeSilva Binodh
Published: March 2010

Current guidance documents for the assessment of analytes and their metabolites in biological fluids are focused on the quantification of small molecules using chromatographic and mass spectrometry platforms. These guidelines come short in immunoassays that confer practicality and specificity associated with antibody binding of analytes from biological fluids. This article focuses on analytical considerations of immunoassays for macromolecules, such as assessment parameters, partial validation, method transfer, cross‐validation, total error, and documentation.
Chromatography‐Based Separation of Proteins, Peptides, and Amino Acids
Authors: Moebius Jan , Swart Remco , Sickmann Albert
Published: March 2010

Since the first commercial introduction of high performance liquid chromatography (HPLC), it has gained wide popularity, resulting in a phenomenal increase of successful applications described in literature. HPLC is a highly efficacious method in peptide and protein analysis especially for the preparation of samples for further analysis by electrospray mass spectrometry. This article focuses on the analytical aspects of liquid chromatography of biomolecules from amino acids to proteins.
Bioanalytical Method Validation for Macromolecules
Authors: Scriba Gerhard K. E.
Published: March 2010

Analytical methods employed for the quantitative determination of drug substances and their metabolites in biological media play a significant role in the evaluation and interpretation of pharmacokinetic data. Small, “conventional” drug molecules are preferentially analyzed by chromatographic techniques and most emphasis has been on the validation of bioanalytical methods for such molecules. This article focuses on various validation issues associated with macromolecule bioanalysis and guidelines issued by regulatory authorities for bioanalytical method validation.
Microarrays in Drug Discovery and Development
Authors: Kumble Krishnanand D. , Kumble Sarita
Published: March 2010

Microarrays are grids of biomolecules in which each element of the grid performs a specific assay such as identification of a specific binding molecule or measuring a particular enzymatic activity. The potential of microarrays to facilitate global analysis of genes and gene products has led to its adoption in nearly every area of biological science—from basic research to clinical diagnostics. This article provides a technical overview of microarrays including information on array formats, production, and use of microarrays for interrogating various molecular species such as DNA, RNA, and proteins.
Proteins: Hormones, Enzymes, and Monoclonal Antibodies—Background
Authors: Materi Wayne , Gombos Zoltan , Wishart David S.
Published: March 2010

The human body is the collection of our own, endogenously produced enzymes, hormones, and antibodies that are responsible for maintaining homeostasis, stabilizing wounds, fighting infections, neutralizing toxins, keeping cancerous cells in check, and generally keeping us alive. Most of today's protein pharmaceuticals fall into 5 general classes, including hormones, vaccines, antibiotics, antibodies, and enzymes. This article describes the general features of pharmaceutically important hormones, antibodies, and enzymes.
Development and Characterization of High‐Affinity Anti‐TopotecanIgGand Fab Fragments
Authors: Chen Jin , Balthasar Joseph P.
Published: March 2010

Anti‐drug antibodies are increasingly being used within an inverse targeting strategy to increase the pharmacokinetic and therapeutic selectivity of intraperitoneal (i.p.) chemotherapy. The anti‐topotecan (TPT) antibodies have demonstrated high affinity and sufficient purity for use in evaluating their use in “inverse targeting” strategies to optimize TPT i.p. chemotherapy. This article describes the development of hybridomas secreting monoclonal antibodies against TPT, and the production, purification, characterization, and pharmacokinetics of an anti‐TPT monoclonal antibody and of monoclonal anti‐TPT Fab fragments.
Recombinant Antibodies for Pathogen Detection and Immunotherapy
Authors: Pokorny Nicholas J. , Boulter‐Bitzer Jeanine I. , Hall J. Chris , Trevors Jack T. , Lee Hung
Published: March 2010

In recent years, there has been increasing interest in developing recombinant antibodies (rAb) for immunodiagnostics and immunotherapeutical applications. Recombinant DNA technology and antibody engineering have increased the available avenues of antibody use, particularly in the application of immunotherapies. This chapter focuses on new developments in rAb with a particular emphasis in pathogen detection and immunotherapy.
The Radiopharmaceutical Science of Monoclonal Antibodies and Peptides for Imaging and Targeted
In Situ
Radiotherapy of Malignancies
Authors: Reilly Raymond M.
Published: March 2010

Radiolabeled monoclonal antibodies (mAbs) and peptides offer the opportunity for molecular imaging of tumors in order to probe their phenotypic properties. Various strategies are being used for labeling these biomolecules with single gamma‐photon‐emitters or positron‐emitters for single‐photon emission computerized tomography (SPECT) and positron‐emission tomography (PET) imaging, respectively. This article focuses on the radiopharmaceutical science that provides the foundation for these biomolecules, mAbs and peptides, for targeting radionuclides to tumors.
Gene Therapy—Basic Principles and the Road from Bench to Bedside
Authors: Rubanyi Gabor M.
Published: March 2010

Human gene therapy (HGT) is defined as the transfer of nucleic acids to somatic cells of a patient, which results in a therapeutic effect by correcting genetic defects, overexpressing proteins, or inhibiting the production of “harmful” proteins. In most applications, gene therapy represents a new, innovative drug delivery system making use of the technical and scientific advances of the last two decades in microbiology, virology, organic chemistry, molecular biology, biochemistry, cell biology, genetics, genomics, and genetic engineering. This article focuses on basic principles, development, and applications of gene therapy.
Formulations and Delivery Limitations of Nucleic‐Acid‐Based Therapies
Authors: Segura Tatiana
Published: March 2010

Gene delivery has expanded to include the delivery of small interfering RNA (siRNA) and oligonucleotides (ON), which can be used to decrease or downregulate the expression of a target protein. An effective gene delivery system can protect the nucleic acid from degradation, target the appropriate cell population, be efficiently internalized by the cell, avoid degradative pathways, and ultimately localize to the nucleus (DNA) or cytosol. This article focuses on systemic injection formulations, direct injection formulations, matrix‐based delivery, and limitations of nonviral nucleic acid delivery.
RNA
Interference: The Next Gene‐Targeted Medicine
Authors: Oleinikov Andrew V. , Gray Matthew D.
Published: March 2010

The newest laboratory method for modulating gene expression, RNA interference (RNAi), has gained rapid interest throughout the world of molecular research, and is being actively pursued as the next “gene‐targeted medicine.” RNAi is a process in which double‐stranded RNA (dsRNA) directs the specific degradation of a corresponding target mRNA. This article describes the main ideas, approaches, and technological directions that may guide the medical researcher interested in using RNAi methodologies to identify and develop new drug candidates.
Delivery Systems For Peptides/Oligonucleotides And Lipophilic Nucleoside Analogs
Authors: Schwendener R.A. , Schott Herbert
Published: March 2010

Drug delivery systems (DDS) are developed for drugs with nonideal properties, such as poor solubility, tissue damage, and loss of drug activity after administration. The formulation of pharmacologically active drug molecules in DDS can improve or abolish toxic side effects and suboptimal therapeutic effects. This article focuses on DDSs for the delivery of peptides, DNA, plasmids, oligodeoxynucleotides, siRNA, and lipophilic nucleoside derivatives.
Production and Purification of Adenovirus Vectors for Gene Therapy
Authors: Prazeres D. M. F. , Santos J. A. L.
Published: March 2010

Gene therapy is a simple and attractive process which consists of the introduction of one or more functional genes in a human or non‐human receptor. Most recombinant viral vectors used in gene therapy clinical trials belong to adenovirus, retrovirus/lentivirus, pox/vaccinia virus, and adeno‐associated virus. This article focuses on adenovirus vector for gene therapy.
Assessing Gene Therapy By Molecular Imaging
Authors: Delépine Pascal , Férec Claude
Published: March 2010

Gene therapy consists of over expressing a functional gene, replacing a mutated gene or expressing an exogenous gene with the aim of correcting a malfunction, inducing an immune response or stimulating angiogenesis. Molecular imaging approaches can be used to observe, understand and document all phenomena involved in gene transfer. This article focuses on various imaging methods for gene therapy, including positron emission tomography (PET), single‐photon emission computed tomography (SPECT), bioluminescence, magnetic resonance imaging (MRI), and gamma imaging.
Comparability Studies for Later‐Generation Products—Plant‐Made Pharmaceuticals
Authors: Stewart Patrick A.
Published: March 2010

Plant Made Pharmaceuticals (PMPs) use genetically engineered plants to express substances that may be used to treat and cure diseases such as cancer, Alzheimer's disease, diabetes, HIV, heart disease. The boundary technology nature of PMPs places it firmly into limbo in terms of social acceptability and, ultimately, economic viability. This article explores PMPs and their potential with an eye toward public response and policy actions.
Biosimilars
Authors: Schellekens H. , Jiskoot W. , Crommelin D.J.A.
Published: March 2010

A biosimilar is defined as any therapeutic protein by its own manufacturing process that may influence the characteristics of the product itself. The producers of biosimilars therefore need to demonstrate consistency and robustness of their production process. This article focuses on main elements and guidelines for producing biosimilars.
The Promise of Individualized Therapy
Authors: Oettel Michael
Published: March 2010

The rapid progress in molecular medicine has sought to understand the molecular basis of human disease with an ultimate goal of developing rationally designed therapies. Pharmacogenetics and pharmacogenomics are the two recent developments to investigate inter‐individual variations of drug response. This article focuses on the issues related to pharmacogenetics and pharmacogenomics.
An Overview of Metabonomics Techniques and Applications
Authors: Lindon John C.
Published: March 2010

Metabonomics is the comprehensive and simultaneous systematic profiling of metabolite levels and their temporal changes in whole organisms. The main analytical techniques employed for metabonomic studies are based on nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). This article describes types of samples, applications, and technologies used in metabonomics.
Radiopharmaceutical Manufacturing
Authors: Farstad Brit S. , Peñuelas Iván
Published: March 2010

Radiopharmacy is a patient‐oriented science that includes the scientific knowledge and professional judgment required to improve and promote health through assurance of the safe and efficacious use of radiopharmaceuticals. Radiopharmacy encompasses studies related to the pharmaceutical, chemical, physical, biochemical, and biological aspects of radiopharmaceuticals. This article focuses on the design, preparation, and quality control of radiopharmaceuticals, radiopharmaceutical chemistry and issues related to the management, selection, storage, dispensing, and proper use of radiopharmaceuticals.
Packaging and Labeling
Authors: Santoro Maria Inês Rocha Miritello , Singh Anil Kumar
Published: March 2010

The role of packaging and labeling in the pharmaceutical industry has grown substantially over the past decade. The packaging of a pharmaceutical product fulfils a variety of roles, such as product presentation, identification, convenience, and protection until administration or use. This article discusses the importance of the packaging and labeling of pharmaceutical preparations.
Clean‐Facility Design, Construction, and Maintenance Issues
Authors: Schneider Raymond K.
Published: March 2010

Successful pharmaceutical manufacturing plant projects incorporate practices that promote flow of the construction process toward completion on time and within budget. Engineering the clean room in accordance with recognized industry practice would produce construction documents that facilitate clear procurement and construction planning as well as a focused, efficient, construction effort. This article focuses on design, construction, and maintenance issues associated with clean‐room construction projects.
Solid Dosage Forms
Authors: Conway Barbara R.
Published: March 2010

Drug substances are most frequently administered as solid dosage formulations, mainly by the oral route. Tablets and capsules are the most frequently used solid dosage forms and are unit dosage forms, comprising a mixture of ingredients presented in a single rigid entity. This article describes the characteristics and applications of different types of solid dosage forms, including, tablets, lozenges, and chewing gums.
Semisolid Dosages: Ointments, Creams, and Gels
Authors: Mahalingam Ravichandran , Li Xiaoling , Jasti Bhaskara R.
Published: March 2010

Semisolid dosage forms are traditionally used for treating topical ailments. Various categories of drugs such as antibacterials, antifungals, and antivirals are incorporated into these products, which show their activity on the surface layers of tissues or penetrate into internal layers to reach the site of action. This article focuses on the formulation, evaluation, and regulatory features of ointments, creams, and gels.
Liquid Dosage Forms
Authors: Rubio‐Bonilla Maria V. , Londono Roberto , Rubio Arcesio
Published: March 2010

Liquid dosage forms are designed to provide the maximum therapeutic response in a target population with difficulty swallowing tablets and capsules and/or to produce rapid therapeutic effects. Commercial liquid dosage forms reach large‐scale production after being preformulated at the laboratory level followed by formulation at the small scale and then at the pilot plant scale. This article focuses on different types of liquid dosage forms and critical aspects of liquids manufacturing process.
Liposomes and Drug Delivery
Authors: Antimisiaris Sophia G. , Kallinteri Paraskevi , Fatouros Dimitrios G.
Published: March 2010

Liposomes are vesicles in which an aqueous volume is entirely surrounded by a phospholipid membrane and their size can range between 30 and 50 nm up to several micrometers. Liposomes serve as a drug delivery system because of their versatile structure and because they are nontoxic, nonimmunogenic, and fully biodegradable. This chapter focuses on basic characteristics and applications of liposomes, their fate after in vivo administration by different routes, and other possible routes for in vivo administration of liposomes.
Biodegradable Nanoparticles
Authors: Chakravarthi Sudhir S. , Robinson Dennis H.
Published: March 2010

Biodegradable nanoparticles are a very active area of research in drug delivery, imaging, and diagnostics. The use of nanoparticles in drug delivery and nanomedicine necessitate use of biocompatible and biodegradable polymeric carriers for parenteral administration. This article focuses on the application of nanotechnology to deliver therapeutic or diagnostic agents using biodegradable polymeric nanoparticles for systemic, localized, or targeted delivery.
RecombinantSaccharomyces Cerevisiaeas New Drug Delivery System to Gut: In Vitro Validation and Oral Formulation
Authors: Blanquet Stéphanie , Alric Monique
Published: March 2010

The development of recombinant deoxyribonucleic acid (DNA) technology has allowed the emergence of novel applications such as drug production directly in the human digestive environment (“in situ”) by ingested living recombinant microorganisms. Genetically engineered microorganisms offer several advantages over classical dosage forms, such as protection of active compounds and regulation of gene expression. This article focuses on the concept and applications of biodrug, scientific feasibility of biodrug concept using yeast as vector, and oral formulation of recombinant yeasts.
Aerosol Drug Delivery
Authors: Hindle Michael
Published: March 2010

Aerosol drug delivery to the lungs has long been the route of choice for the treatment of respiratory diseases, including asthma and chronic obstructive airway disease. Metered dose inhalers (MDIs), dry powder inhalers (DPIs), and nebulizers have been employed to successfully deliver a wide range of pharmaceuticals principally to the lungs for local action. This article focuses on aerosol drug delivery devices, their development, and future prospects for pulmonary administration.
Ocular Drug Delivery
Authors: Rupenthal Ilva D. , Alany Raid G.
Published: March 2010

Due to the accessibility of the eye surface, topical administration of ophthalmic medications is the most common method for treating conditions affecting the exterior eye surface. Various ocular delivery systems, such a ointments, suspensions, micro‐ and nanocarriers, and liposomes, have been investigated during the past two decades. This article focuses on the topical application of drugs to the surface of the eye and discusses the most recent formulation approaches in this area.
Microemulsions as Drug Delivery Systems
Authors: Alany Raid G. , Wen Jingyuan
Published: March 2010

Microemulsions (ME) represent an exciting opportunity for pharmaceutical formulators and drug delivery scientists. They can accommodate drugs of different physicochemical properties and protect those that are labile. This article focuses on the historical background, structure, formation, and pharmaceutical formulation of microemlsions, their application as drug delivery systems, and techniques used to characterize ME.
Transdermal Drug Delivery
Authors: Asbill C. Scott , Bumgarner Gary W.
Published: March 2010

During the last decade there has been an explosion of drug candidates in clinical trials and a high number of dosage forms approved by the U.S. FDA that utilize the transdermal route of drug delivery. The interest in transdermals can be attributed to the advantages of maintaining steady‐state drug concentrations and bypassing first‐pass metabolism, and mimicking an intravenous (IV) infusion. This article focuses on drug candidates for transdermal drug delivery, transdermal patch design, commercially available patches, and various approaches to transdermal delivery.
Vaginal Drug Delivery
Authors: das Neves José , Amaral Maria Helena , Bahia Maria Fernanda
Published: March 2010

The vagina has been used for a long time as a route for drug administration. Vaginal drug delivery has seen recent advances that make it very promising, in particular therapeutic fields such as the prevention of human immunodeficiency virus (HIV) and other sexually transmitted infections, and contraception. This article discusses the main features of vaginal anatomy, physiology, and histology related to drug delivery as well as vaginal drug delivery systems and their evaluation, current usage of the vagina as a route of drug administration, and promising strategies in this field.
Pharmaceutical Preformulation: Physicochemical Properties of Excipients and Powders and Tablet Characterization
Authors: Lee Beom‐Jin
Published: March 2010

Tablet is a major category of solid dosage forms which are widely used worldwide. Based on preformulation studies, the optimal dosage forms are generally decided. This article focuses on general preformulation approaches for tablet production, physicochemical properties of drug and excipients, and types and functions of excipients used for tablet formulation and drug–excipient incompatibility.
Role of Preformulation in Development of Solid Dosage Forms
Authors: Perumal Omathanu P. , Podaralla Satheesh K.
Published: March 2010

Preformulation testing has a significant role in a drug discovery and development program, as it provides valuable feedback to the various discovery and development teams in enabling druggability during lead identification and optimization. In a generic setting, preformulation studies are mainly focused on developing a formulation that is bioequivalent to the innovator's product with the main objective of filing an abbreviated new drug application (ANDA). This article focuses on preformulation testing for oral solid dosage forms in a drug discovery setting.
Modeling and Informatics in Drug Design
Authors: Picker‐Freyer Katharina M
Published: March 2010

Tablet production systems can be defined as all machines which are able to produce tablets. Tablet production systems include tableting machines for production and research as well as tableting machine simulators, which are able to mimic the production processes of tableting machines to facilitate scale‐up. This article focuses on instrumentation of tablet production systems, tableting process, and the different techniques used for production and research of tablets.
Controlled Release of Drugs from Tablet Coatings
Authors: Altinkaya Sacide Alsoy
Published: March 2010

Controlled‐release technology for drug delivery applications is designed to target the drug to particular places or cells in the body and to control the duration and level of the drug in the body within a specified therapeutic window. Controlled‐release dosage forms provide sustained drug release and require less frequent drug loading than conventional forms. This article presents a review of manufacturing methods for the application of coating materials on tablets, characterization methods used to evaluate tablet coatings, techniques used for manufacturing asymmetric‐type membranes, and modeling approaches employed for optimization of the tablet coating formulations.
Effects of Grinding in Pharmaceutical Tablet Production
Authors: Andrews Gavin , Jones David , Zhai Hui , Abu Diak Osama , Walker Gavin
Published: March 2010

The importance of size reduction in relation to pharmaceutical active agents and excipients is well known. A variety of types of equipment are used for milling, such as ball mill and fluid energy mill. This article focuses on particle size reduction methods, characterization of particle size and shape, the importance of controlling particle characteristics to ensure the success of pharmaceutical powder processing, and the manufacture of elegant pharmaceutical products.
Cyclodextrin‐Based Nanomaterials in Pharmaceutical Field
Authors: Bilensoy Erem , Hincal A. Atilla
Published: March 2010

Cyclodextrins (CDs) have a wide range of application in the pharmaceutical field due to their unique structure, which allows them to include hydrophobic molecules in their apolar cavity and to mask the physicochemical properties of the included molecule. CDs have also been incorporated into nanoparticulate drug delivery systems for complexation of active ingredient and modification of CDs to render an amphiphilic character to these molecules. This article focuses on the issues concerning the use of CDs and derivatives as nanomaterials for drug delivery and application of CDs in nanoparticulate drug delivery systems.
Pharmaceutical Nanosystems: Manufacture, Characterization, and Safety
Authors: Chowdhury D. F.
Published: March 2010

Nano‐pharmaceutical systems generally imply products that may in their own right or in combination with another moiety bring about therapeutic benefit. Nanosystems can be classified in a number of ways, for example, according to their elemental composition, according to size, structure, and function, or according to a structure‐function relationship. This article focuses on the manufacture, characterization, and safety of pharmaceutical nanosystems.
Good Manufacturing Practices (
GMP
) and Related
FDA
Guidelines
Authors: Harris James R.
Published: March 2010

All food‐ and drug‐related laws in the United States are contained in Title 21 of the Code for Federal Regulations (CFR). Apart from these laws, Food and Drug Administration (FDA) publishes guidance documents on good manufacturing practices (GMP) for drug manufacturers. This article focuses on laws contained in Title 21 of the CFR, and the related FDA guidelines for GMP.
Enforcement of Current Good Manufacturing Practices
Authors: Nolan Kenneth J.
Published: March 2010

The drug manufacturers in the U.S. should conform to current good manufacturing practice (cGMP) regulations contained in Title 21 of the U.S. Code of Federal Regulations (CFR), Parts 210 and 211. The Food and Drug Administration (FDA) and other regulatory agencies are responsible for the enforcement of the cGMP regulations. This article focuses on the cGMP regulations enforcement agencies and the techniques of enforcement.
Creating and Managing a Quality Management System
Authors: Arling Edward R. , Dowling Michelle E. , Frankel Paul A.
Published: March 2010

A comprehensive quality management system (QMS) has become an integral part of pharmaceutical and biopharmaceutical operations due to increased market demand and business competition. A well‐designed QMS, with mature, developed processes, provides the required infrastructure and support for successful manufacturing operations. This article provides an understanding of QMS to succeed in pharmaceutical manufacturing operation.
Origin of Contamination
Authors: Bohrer Denise
Published: March 2010

Contaminants in pharmaceutical products can be classified in to related substances and process contaminants. Related substances are structurally related to the drug substance, while process contaminants are introduced during manufacturing or handling procedures. This article focuses on the types of contaminants and their origins.
Stability and Shelf Life of Pharmaceutical Products
Authors: Velagaleti Ranga
Published: March 2010

The U.S. Pharmacopeia (USP) defines stability of pharmaceutical products as the extent to which a product retains, within specified limits and throughout its period of storage and use, the same properties and characteristics that it possessed at the time of manufacture. Stability is determined by evaluation of the quality parameters with time under the influence of a variety of environmental factors such as temperature, humidity, and light. This article focuses on the stability and shelf life of pharmaceutical drug products.
Drug Stability
Authors: Ramirez‐Beltran Nazario D. , Rodriguez Harry , Estévez L. Antonio
Published: March 2010

The U.S. Food and Drugs Administration (FDA) and the International Conference on Harmonization (ICH) require that pharmaceutical companies present factual evidence supporting the shelf life for either existing or new products. The expiration date provides the consumer the confidence that the drug product will retain its identity, strength, quality, and purity throughout the expiration period. This article describes a set of practical tools to design a stability study as well as to discuss and illustrate how to determine the shelf life for a given drug product.
Effect of Packaging on Stability of Drugs and Drug Products
Authors: Akala Emmanuel O.
Published: March 2010

Governing bodies as well as pharmaceutical companies are paying great attention on stability of drug products to enable delivery of the products to the final consumer in good quality. Packaging plays a major role in providing stability to the pharmaceutical products. This article discusses factors influencing stability of drugs and the techniques of packaging to maintain stability of the products.
Pharmaceutical Product Stability
Authors: Webster Andrew A.
Published: March 2010

Pharmaceutical product stability may be defined as the capability of a particular formulation to remain within its physical, chemical, microbiological, therapeutic, and toxicological specifications while in a specific container closure system. There are many factors that can affect the stability of a pharmaceutical product. These include the stability of the active drug(s), interactions between active and inactive ingredients, the dosage form, manufacturing process, the container system, and environment for shipping, handling, and storage. This article focuses on the different types of pharmaceutical product stability, such as chemical degradation, physical degradation, and microbial degradation.
Alternative Accelerated Methods for Studying Drug Stability: Variable‐Parameter Kinetics
Authors: Alibrandi Giuseppe
Published: March 2010

Studies on drug stability have a central role in physicochemical profiling. A fast screening of new molecular entities and low‐time‐consuming detailed studies on selected candidates can avoid delay and consequent high cost in the first part of pharmaceutical investigation. This article focuses on variable‐parameter kinetics (VPaK) method for studying stability of drug products.
Analytical Method Validation: Principles and Practices
Authors: Chan Chung Chow
Published: March 2010

Validation of an analytical procedure is the process by which it is established that the performance characteristics of the procedure meet the requirements for its intended use. All analytical methods that are intended to be used for analyzing any clinical samples need to be validated. This article focuses on the requirements of analytical method validation and the options that are available to allow for optimal utilization of analytical resources in a development laboratory.
Validation of Laboratory Instruments
Authors: Lam Herman
Published: March 2010

In recent years, tremendous efforts have been put forth by many organizations to address the validation of a wide variety of laboratory instruments of varying complexity. The fundamental purpose of validating laboratory instruments is to provide assurance that the instrument is suitable for its intended use. This article provides an overview of laboratory instrument validation for GMPs and GLPs.
Pharmaceutical Manufacturing Validation Principles
Authors: Souto E. B. , Vasconcelos T. , Ferreira D. C. , Sarmento B.
Published: March 2010

The pharmaceutical industry has been a leader in the development of quality and safety procedures assuring that the risk of its work is reduced to a minimum. Validation is an integral part of quality assurance, involving the methodical study of systems, facilities, and processes aimed at determining whether they perform their intended functions adequately and consistently as specified. This article focuses on the pharmaceutical industry validation system.
Fire Safety
Authors: Delichatsios Michael A.
Published: March 2010

As a chapter on fire safety in a combustion handbook may be either a high level generic document or a treatise on a specific area, this chapter takes the “middle road,” outlining the types of data required for fire safety design. The references [1–3] included provide both a generic perspective and aspects of actual practice, as well as sources of data needed for fire safety engineering. The chapter includes a description of context and purpose for fire safety engineering, a classification of the data, and list of data including possible sources and comments as needed. The references [1–13] address in part the reliability and confidence in these data. As a promising near future development, some recent efforts to make risk assessment more accessible and to integrate fire protection engineering with the building design using software agents, has been included. Additional related information regarding data on safety is included in Chapters18,20and23of this volume of the Handbook.
Non‐Optical Lithography
Authors: Sotomayor Torres Clivia M. , Ahopelto Jouni
Published: March 2010

An example of non‐optical lithographies is nanoimprint lithography. The state of the art in this versatile nanofabrication method is reviewed, including the scientific challenges, such as nano‐scale rheology and mechanical stability, and engineering challenges, such as the competing constraints for a high volume production. The latter is coupled to the flexibility and opportunities afforded by the wealth in polymer functionalisation, which makes this family of methods particularly suited for applications in optics, life sciences and material sciences. The chapter also includes an introduction to progress in metrology as well as 3D nanoimprinting.
Nanostructured Probes forIn VivoGene Detection
Authors: Bao Gang , Santangelo Phillip , Nitin Nitin , Rhee Won Jong
Published: March 2010

The ability to visualize in real time the expression dynamics and localization of specific RNAsin vivooffers tremendous opportunities for biological and disease studies, including the detection of cancer. Quantitative methods such as real‐time PCR and DNA microarrays rely on the use of cell lysates, and thus are not able to obtain important spatial and temporal information. Fluorescent proteins and other reporter systems cannot image endogenous RNA in living cells. Fluorescencein situhybridization (FISH) assays require washing to achieve specificity, and therefore can only be used with fixed cells. In this chapter we review the recent development of nanostructured probes for living cell RNA detection, and discuss the biological and engineering issues and challenges of quantifying gene expressionin vivo. In particular, we describe methods that use oligonucleotide probes, combined with novel delivery strategies, to image the relative level, localization and dynamics of RNA in live cells. Examples of detecting endogenous mRNAs, as well as imaging their subcellular localization, are given to illustrate the biological applications. Issues in probe design, delivery and target accessibility are also discussed. The nanostructured probes promise to open new and exciting opportunities in sensitive gene detection for a wide range of biological and medical applications.
Hydrogenases and Alternative Energy Strategies
Authors: Rüdiger Olaf , De Lacey António L. , Fernández Victor M. , Cammack Richard
Published: March 2010

This chapter considers the hydrogenases, the enzymes that produce and consume molecular hydrogen; how they work and how they might be exploited in a future hydrogen‐based economy. Hydrogenases are enzymes containing iron and in some cases nickel, which efficiently couple the proton‐hydrogen couple to the reduction or oxidation of electron carriers. They have many metabolic functions in the microbial world. Much has been learned from recent research about their active sites and mechanism of action. There are three known types of hydrogenase chemistry: that based on a dinuclear nickel‐iron site (NiFe‐and NiFeSe‐hydrogenases); on more complex iron‐containing clusters (FeFe‐hydrogenases); and an enzyme containing a mononuclear iron site, which catalyzes a specific direct hydrogenation of a cofactor (Hmd). Variations on the NiFe‐hydrogenases are involved in the sensing of H2in cell regulation. Where necessary, hydrogenases have structural features that avoid the inhibitory effects of oxygen, carbon monoxide and other pollutant gases which poison other catalysts such as platinum. The structures of the different types of hydrogenases have been determined and their catalytic mechanisms investigated by spectroscopy and electrochemistry. Genetic and biochemical studies are elucidating the complex metabolic pathways by whereby the different types of hydrogenase catalytic centers are assembled. Three possible energy strategies are suggested by hydrogenase research: (1) hydrogen biotechnology, using microorganisms to produce hydrogen by fermentation of organic wastes, with or without the assistance of photosynthesis; (2) biomimicry, using insights from the structures and mechanisms of hydrogenases to synthesize improved catalysts as a substitute for the limited resources of precious metals; and (3) harnessing hydrogenases on carbon electrodes in electrolysis cells for H2production or fuel cells to produce electricity from hydrogen at low concentrations and with low overpotentials and at rates comparable to those with platinum.
Photochemical and Photo‐induced Reactions in Supercritical Fluid Solvents
Authors: Tanko James M.
Published: March 2010

The sections in this article are

Introduction

“Solvent” Properties of Supercritical Fluids

Scope of This Chapter

Experimental Considerations

Photochemical Reactions in Supercritical Fluid Solvents

Geometric Isomerization

Photodimerization

Carbonyl Photochemistry

Photosensitization and Photo‐induced Electron Transfer

Photo‐oxidation Reactions

Photo‐initiated Radical Chain Reactions in Supercritical Fluid Solvents

Free Radical Brominations of Alkyl Aromatics in Supercritical Carbon Dioxide

Free Radical Chlorination of Alkanes in Supercritical Fluid Solvents

Conclusion

Acknowledgment