A pharmaceutical scientist's approach toward solubility enhancement of a poorly water-soluble molecule typically includes detailed characterization of the compound's physiochemical properties, solid-state modifications, advanced formulation design, non-conventional process technologies, advanced analytical characterization, and specialized product performance analysis techniques. The scientist must also be aware of the unique regulatory considerations pertaining to the non-conventional approaches often utilized for poorly water-soluble drugs. One faced with the challenge of developing a drug product from a poorly soluble compound must possess at minimum a working knowledge of each of the abovementioned facets and detailed knowledge of most. In light of the magnitude of the growing solubility problem to drug development, this is a significant burden especially when considering that knowledge in most of these areas is relatively new and continues to develop. There are numerous literature resources available to pharmaceutical scientists to educate and provide guidance toward formulations development with poorly water-soluble drugs; however, a single, comprehensive reference is lacking. Furthermore, without access to a vast journal library, the detailed methods used to implement these approaches are not available. The objective of this volume is therefore to consolidate within a single text the most current knowledge, practical methods, and regulatory considerations pertaining to formulations development with poorly water-soluble molecules.

Autorentext

Robert O. (Bill) Williams III, Ph.D. is the Johnson & Johnson Centennial Professor of Pharmaceutics at the College of Pharmacy, University of Texas at Austin. He earned a B.S. in Biology from Texas A&M University, a B.S. in Pharmacy from the University of Texas at Austin and Doctor of Philosophy in Pharmaceutics in 1986 from the University of Texas at Austin. Dr. Williams worked 9 years in the pharmaceutical industry in the United States and France before returning to the University of Texas at Austin. Dr Williams was elected a Fellow of the American Association of Pharmaceutical Scientists in 2006 and a Fellow of the American Institute of Medical and Biological Engineering in 2008. Dr. Williams is a member of numerous professional organizations, including American Association of Colleges of Pharmacy, and American Association of Pharmaceutical Scientists. Dr. Williams' research interests include development of novel drug delivery systems for oral, pulmonary, nasal, injectable, buccal and topical applications, development of novel particle engineering technologies for low molecular weight drugs, peptides and proteins, and analytical technologies to characterize actives, excipients and polymers. He has published over 300 articles, abstracts and book chapters in the fields of pharmaceutical technology and drug delivery. In addition, Dr. Williams has co-edited one book. He is an inventor on numerous patents and patent applications. Dr. Williams is the Editor-in-Chief of the research journal Drug Development and Industrial Pharmacy, and serves as a reviewer for International Journal of Pharmaceutics, Pharmaceutical Research, European Journal of Pharmaceutics and Biopharmaceutics, S.T.P. Pharma Sciences, AAPS PharmSciTech, Journal of Pharmaceutical Sciences, Pharmaceutical Development and Technology, Journal of Membrane Science, and Journal of ControlledRelease.

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Alan B. Watts, Ph.D. is the Assistant Director of the Drug Dynamics Institute and an Adjunct Assistant Professor at the College of Pharmacy, University of Texas at Austin. He earned a B.S. in Biomedical Engineering from Louisiana Tech University and Doctor of Philosophy in Pharmaceutics from the University of Texas at Austin where he was an AAPS/AFPE Pre-Doctoral Fellow. His research efforts have focused on novel approaches toward pulmonary drug delivery, translational science, and formulation of insoluble drugs. Previously, Alan worked as a Research Scientist in the pharmaceutical industry specializing in drugs for dry powder delivery to the lungs.

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Dave Miller, Ph.D. is a Senior Principal Scientist in the Pharmaceutical and Analytical Research and Development Department at Hoffmann-La Roche, Inc. in Nutley, NJ. He earned his B.S. in Chemical Engineering in 2002 and his Ph.D. in Pharmaceutics in 2007 from the University of Texas at Austin. Throughout his academic and industrial career, Dr. Miller's research focus has been in the area of solubility enhancement; specifically, advanced solid dispersion systems, hot-melt extrusion technology, spray drying technology, precipitation technology, and the development of in-vitro/in-vivo relationships. He has published numerous research articles, two book chapters, and is a co-inventor on several patent applications pertaining to this field.

Zusammenfassung

This volume is intended to provide the reader with a breadth of understanding regarding the many challenges faced with the formulation of poorly water-soluble drugs as well as in-depth knowledge in the critical areas of development with these compounds. Further, this book is designed to provide practical guidance for overcoming formulation challenges toward the end goal of improving drug therapies with poorly water-soluble drugs. Enhancing solubility via formulation intervention is a unique opportunity in which formulation scientists can enable drug therapies by creating viable medicines from seemingly undeliverable molecules. With the ever increasing number of poorly water-soluble compounds entering development, the role of the formulation scientist is growing in importance. Also, knowledge of the advanced analytical, formulation, and process technologies as well as specific regulatory considerations related to the formulation of these compounds is increasing in value. Ideally, this book will serve as a useful tool in the education of current and future generations of scientists, and in this context contribute toward providing patients with new and better medicines.

Inhalt

Route-Specific Challenges in Delivery of Poorly Water Soluble Drugs.- Optimizing the Formulation of Poorly Water Soluble Drugs.- Solid-State Techniques for Improving Solubility.- Mechanical Particle Size Reduction Techniques.- Solubilized Formulations.- Injectable Formulations of Poorly Water Soluble Drugs.- Design and Development of Self-Emulsifying Lipid Formulations for Improving Oral Bioavailability of Poorly Water-Soluble and Lipophilic Drugs.- Structured Development Approach for Amorphous Systems.- Melt Extrusion.- Spray Drying Technology.- Pharmaceutical Cryogenic Technologies.- Precipitation Technologies for Nanoparticle Production.- Emerging Technologies to Increase the Bioavailability of Poorly Water Soluble Drugs.- Regulatory Considerations for Development and Commercialization of Poorly Water Soluble Drugs.