Cover Page

Contents

Title Page

Dedication

ITHACA (Konstantinos Kavafis, 1911)

This book is dedicated to my wonderful wife Eleni-Angeliki and my lovely son George-Alexander and daughter Eugenia-Erene. I thank them for their continuous support and patience.

List of Contributors

Jessica Albers, Evonik Industries AG, Kirschenallee, 64293 Darmstadt

Ana Almeida, Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium

Joshua Boateng, University of Greenwich, School of Science, Medway Campus, Central Avenue, ME4 4TB, Kent, UK

Bart Claeys, Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium

Dennis Douroumis, University of Greenwich, School of Science, Medway Campus, Central Avenue, ME4 4TB, Kent, UK

Adam Dreiblatt, Century Extrusion, 2412 W. Aero Park Ct., Traverse City, MI 49686 USA

Tom Geilen, Thermo Fisher Scientific, Dieselstrasse 4, 76227 Karlsruhe, Germany

Thobias Geissler, Thermo Fisher Scientific, Dieselstrasse 4, 76227 Karlsruhe, Germany

Costas G. Gogos, Department of Chemical, Biological, and Pharmaceutical Engineering New Jersey Institute of Technology, Newark, NJ, USA

Andreas Gryczke, Ernst-Ludwig-Straße 19a, 64560 Riedstadt, Germany

Sandra Guns, Laboratory of Pharmacotechnology and Biopharmacy, Catholic University of Leuven Campus Gasthuisberg O & N2, Herestraat 49, 3000 Leuven, Belgium

Abhay Gupta, FDA-CDER, Division of Product Quality Research White Oak Life Sciences Building 64, 10903 New Hampshire Ave, Silver Spring, MD 2099, USA

Mark Hall, The Dow Chemical Company, Midland Michigan, US

Chris Heil, Thermo Fisher Scientific, 5225 Verona Rd, Madison, WI 53711 USA

Pernille Høyrup Hemmingsen, Egalet Ltd, DK-3500 Værløse, Denmark

Jeffrey Hirsch, Thermo Fisher Scientific, 5225 Verona Rd, Madison, WI 53711 USA

Masoor A. Khan, FDA-CDER, Division of Product Quality Research White Oak Life Sciences Building 64, 10903 New Hampshire Ave, Silver Spring, MD 2099, USA

Dirk Leister, Thermo Fisher Scientific, Dieselstrasse 4, 76227 Karlsruhe, Germany

Huiju Liu, Department of Chemical, Biological, and Pharmaceutical Engineering New Jersey Institute of Technology, Newark, NJ, USA

Andrew Loxley, Particle Sciences Inc., 3894 Courtney St #180, Bethlehem PA 18017, USA

Keith Luker, Randcastle Extrusion Systems, Inc., 220 Little Falls Rd. Unit 6 Cedar Grove, NJ 07009

Guy Van den Mooter, Laboratory of Pharmacotechnology and Biopharmacy, Catholic University of Leuven Campus Gasthuisberg O & N2, Herestraat 49, 3000 Leuven, Belgium

Kathrin Nollenberger, Evonik Industries AG, Kirschenallee, 64293 Darmstadt

Michael Read, The Dow Chemical Company, Midland Michigan, US

Martin Rex Olsen, Egalet Ltd., DK-3500 Værløse, Denmark

Jean Paul Remon, Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium

Geert Verreck, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium

Chris Vervaet, Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium

Peng Wang, Department of Chemical Engineering University of Rhode Island, Kingston, RI, USA

Preface

Hot-melt Extrusion (HME) is an emerging continuous processing technology for the development of various solid dosage forms and drug delivery systems. In the last 20 years HME has attracted increased attention from both the pharmaceutical industry and academia. The enormous need for new dynamic manufacturing processes to produce robust finished products makes HME an excellent technology. Although there are several publications on HME applications, this is the first attempt to provide a concrete overview of HME pharmaceutical applications.

The aim of this book is to present a comprehensive review of the theory, instrumentation and wide spectrum of applications. The book is targeted at scientists in academia and industry and graduate students in various research-intensive programs in pharmaceutical sciences and medicine who are dealing with many aspects of drug formulation and delivery, pharmaceutical engineering and processing and polymers and materials science.

Chapters 1 and 2 discuss single- and twin-screw extrusion operational principles, design and critical processing parameters. Chapter 3 is an overview of HME developments in pharmaceutics, and discusses a number of drug delivery systems and physicochemical characterization techniques of HME extrudates. Chapters 4 and 5 deal with theoretical approaches of drug–polymer miscibility estimation and discuss the role, influence and selection of plasticizers in the HME process. Chapters 6 and 7 provide in-depth knowledge of drug products extruded by a wide range of polymers and their applications. More detail is provided in Chapter 8 where the application of HME for the manufacture of thin films is discussed. Chapter 9 is dedicated to the employment of HME for the taste-masking of bitter APIs, and discusses the selection of various excipients for these purposes.

Chapter 10 includes a comprehensive discussion of clinical studies performed by various groups, bioavailability and pharmacokinetics of oral immediate release, oral controlled release and implants. The relatively new manufacturing process of injection molding is introduced in Chapter 11, and aspects such as critical process parameters, excipients, new products and their properties are critically analyzed. A comprehensive discussion of dispersive and distributive mixing is included in Chapter 12 and case studies are presented.

The reader can find important information in Chapter 13 about the scale-up of the hot-melt extrusion process from a lab-scale extruder to a commercial-scale extruder, as well as different scale-up scenarios. Novel applications of HME for the manufacturing of devices and implant systems can be found in Chapter 14, including examples of marketed products.

Chapter 15 is an FDA perspective on HME product and process understanding with special attention given to Quality by Design (QbD) as a tool to understanding HME processing. Finally, Chapter 16 introduces a process analytical technology (PAT) approach by using near-infrared spectroscopy for understanding and controlling the hot-melt extrusion process in the pharmaceutical industry.

I would like to acknowledge the valuable support and cooperation of all the contributing authors throughout this process, to whom I offer a most sincere thank you. Without their dedication and timely submission of material, this book would not have been published.

Dennis Douroumis