Pharmaceutical Amorphous Solid Dispersions

A roadmap to enhance and maximize drug solubility and bioavailability With an increasing number of poorly soluble or difficult to crystallize drugs entering development, new formulation strategies are required to achieve sufficient bioavailability. Amorphous solid dispersions are an option receiving increased attention in recent years, because they can improve dissolution rates and increase solubility characteristics of drug compounds. This book highlights and discusses the advances in developing pharmaceutical amorphous solid dispersions. Chapters, written by contributing authors on the frontlines of R & D, provide a roadmap from early to late stages of drug development. They cover topics that include: physical and chemical properties, screening, scale–up, formulation, drug product manufacture, intellectual property, and regulatory considerations. Pharmaceutical scientists using this book as a guide for formulating their drugs benefit from a number of features, including: •     A comprehensive overview of the amorphous solid dispersion technology, which is a leading technology platform to deliver poorly water soluble drugs – a major hurdle in today’s pharmaceutical industry •     How to apply amorphous solid dispersions techniques to particular pharmaceutical systems •     An appendix with structure and property information for polymers commonly used in drug development and with marketed drugs developed using the amorphous sold dispersion approach •     Global regulatory issues including USA regulations, ICH guidelines, and patent concerns around the world

Contents Contributors Preface Chapter 1: Introduction to Amorphous Solid Dispersions George Zografi and Ann Newman Chapter 2: Polymers and Surfactants Padma Narayan, William W. Porter III, Meinolf Brackhagen, and Christopher Tucker Chapter 3: Amorphous Solid Dispersion Screening Ann Newman Chapter 4: Solid state Characterization of Amorphous Dispersions Frederick G. Vogt Chapter 5: Physical Stability and Crystallization Inhibition Lynne S. Taylor Chapter 6: Solubility and Dissolution Considerations for Amorphous Solid Dispersions Grace A. Ilevbare, Wei Xu, Christopher T. John, James Ormes, Jesse Kuiper, Allen C. Templeton, and Annette Bak Chapter 7: Translational Development of Amorphous Dispersions Patrick Connelly, Brian Patrick Quinn, Steve Johnston, Philip Bransford, Praveen Mudunuri, Andrey Peresypkin, Majed Fawaz, Setu Roday, Anuj Kuldipkumar, Hong–Ren Wang, Phillip Snyder, Jeff Katstra, Tapan Sanghvi, Bill Rowe, and Patricia Hurter Chapter 8: Preclinical and Clinical Studies Marcus E. Brewster, Geert Verreck, Jan Bevernage, Joachim Brouwers, Guy Van den Mooter, and Patrick Augustijns Chapter 9: Spray–Drying and Scale–Up Daniel E. Dobry, Dana M. Settell, and John M. Baumann Chapter 10: Hot Melt Extrusion of Amorphous Solid Dispersions Kieran Crowley and Andreas Gryczke Chapter 11: Formulation Development of Amorphous Dispersions Tapan Sanghvi, Jeff Katstra, Brian Patrick Quinn, Hayden Thomas, and Patricia Hurter Chapter 12: Scientific and Regulatory Considerations in Product Development Abhay Gupta, Ziyaur Rahmna, and Manssor A. Khan Chapter 13: Chapter Patenting Amorphous Solid Dispersions of Pharmaceuticals Jeffry A. Lindeman Chapter 14: Monographs on Polymers and Surfactants Xia Lu, Robert Wenslow, and Ann Newman Appendix 1 Xia Lu, Robert Wenslow, and Ann Newman Appendix 2: Marketed Products Ann Newman

Ann Newman is a pharmaceutical consultant with Seventh Street Development Group, where she provides consulting, training, and webcast services on solid–state pharmaceutics and pharmaceutical development. She is also an Adjunct Professor and Lecturer in the Department of Industrial and Physical Pharmacy at Purdue University. A senior pharmaceutical scientist with demonstrated scientific and leadership expertise in the pharmaceutical industry, Dr. Newman has over 25 years of large pharma and contract research experience.