Table Of Content

Pharmaceutical Extrusion Technology edited by Isaac Ghebre-Sellassie MEGA Pharmaceuticals Asmara, Eritrea and Pharmaceutical Technology Solutions Morris Plains, New Jersey, U.S.A. Charles Martin American Leistritz Extruder Corporation Somerville, New Jersey, U.S.A. Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved. 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For U more information, write to Special Sales/Professional Marketing at the headquarters [ y address above. b d de Copyright DDDDDDDDD2003by Marcel Dekker,Inc. All RightsReserved. a o wnl Neitherthisbooknoranypartmaybereproducedortransmittedinanyformorbyany o means,electronicormechanical,includingphotocopying,microfirming,andrecording, D orbyanyinformationstorageandretrievalsystem,withoutpermissioninwritingfrom the publisher. Currentprinting (last digit): 10 9 8 7 6 5 4 3 2 1 PRINTED INTHE UNITEDSTATESOFAMERICA Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved. DRUGS AND THE PHARMACEUTICAL SCIENCES 4 1 Executive Editor 0 2 ril James Swarbrick p PharmaceuTech, Inc A 1 Pinehurst, North Carolina 2 9 3 6: 0 at ] Advisory Board v di v o Larry L Augsburger David E Nichols Pl University of Maryland Purdue University - s Baltimore, Maryland West Lafayette, Indiana e gi olo Douwe D Breimer Stephen G Schulman n Gorlaeus Laboratories University of Florida h c Leiden, The Netherlands Gainesville, Florida e T d o Trevor M Jones Jerome P Skelly o F The Association of the Alexandria, Virginia of British Pharmaceutical Industry y London, United Kingdom sit r ve Hans E. Jungmger Felix Theeuwes ni Leiden/Amsterdam Center Alza Corporation U [ for Drug Research Palo Alto, California by Leiden, The Netherlands d e d Vincent H L Lee Geoffrey T. Tucker a o University of Southern California University of Sheffield nl w Los Angeles, California Royal Hallamshire Hospital Do Sheffield, United Kingdom Peter G Welling Institut de Recherche Jouvemal Fresnes, France Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved. DRUGS AND THE PHARMACEUTICAL SCIENCES A Series of Textbooks and Monographs 1. Pharmacokmetics, Milo Gibaldi and Donald Perner 4 2. Good Manufacturing Practices for Pharmaceuticals: A Plan for Total 1 20 Quality Control, Sidney H Willig, Murray M. Tuckerman, and William ril S. Hitchings IV Ap 3. Microencapsulation, edited by J. R Nixon 1 4 Drug Metabolism Chemical and Biochemical Aspects, Bernard Testa 2 9 and Peter Jenner 3 6: 5 New Drugs: Discovery and Development, edited by Alan A. Rubin 0 6 Sustained and Controlled Release Drug Delivery Systems, edited by ] at Joseph R. Robinson div 7. Modern Pharmaceutics, edited by Gilbert S. Banker and Christopher v T. Rhodes o Pl 8. Prescription Drugs in Short Supply. Case Histories, Michael A. s - Schwartz e gi 9. Activated Charcoal. Antidotal and Other Medical Uses, David 0. o Cooney ol n 10. Concepts in Drug Metabolism (in two parts), edited by Peter Jenner h c and Bernard Testa e T 11. Pharmaceutical Analysis: Modern Methods (in two parts), edited by d o James W. Munson o F 12. Techniques of Solubilization of Drugs, edited by Samuel H. Yalkow- f o sky y sit 13. Orphan Drugs, edited by Fred E. Karch er 14. Novel Drug Delivery Systems: Fundamentals, Developmental Con- v ni cepts, Biomedical Assessments, Yie W. Chien U 15. Pharmacokmetics: Second Edition, Revised and Expanded, Milo [ y Gibaldi and Donald Perrier b d 16. Good Manufacturing Practices for Pharmaceuticals. A Plan for Total e d Quality Control, Second Edition, Revised and Expanded, Sidney H. a o Willig, Murray M. Tuckerman, and William S Hitchings IV nl w 17. Formulation of Veterinary Dosage Forms, edited by Jack Blodmger Do 18. Dermatological Formulations. Percutaneous Absorption, Brian W Barry 19. The Clinical Research Process in the Pharmaceutical Industry, edited by Gary M. Matoren 20. Microencapsulation and Related Drug Processes, Patrick B. Deasy 21. Drugs and Nutrients' The Interactive Effects, edited by Daphne A. Roe and T. Colin Campbell 22. Biotechnology of Industrial Antibiotics, ErickJ. Vandamme Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved. 23. Pharmaceutical Process Validation, edited by Bernard T. Loftus and Robert A Nash 24 Anticancer and Interferon Agents Synthesis and Properties, edited by Raphael M Ottenbnte and George B Butler 25. Pharmaceutical Statistics. Practical and Clinical Applications, Sanford Bolton 26 Drug Dynamics for Analytical, Clinical, and Biological Chemists, Benjamin J Gudzinowicz, Burrows T Younkin, Jr, and Michael J Gudzmowicz 14 27. Modern Analysis of Antibiotics, edited by Adjoran Aszalos 0 2 28. Solubility and Related Properties, Kenneth C. James ril 29. Controlled Drug Delivery Fundamentals and Applications, Second p A Edition, Revised and Expanded, edited by Joseph R Robinson and 1 Vincent H. Lee 2 9 30 New Drug Approval Process Clinical and Regulatory Management, 3 6: edited by Richard A Guanno 0 31 Transdermal Controlled Systemic Medications, edited by Yie W Chien ] at 32 Drug Delivery Devices Fundamentals and Applications, edited by v di Praveen Tyle v 33 Pharmacokmetics Regulatory • Industrial • Academic Perspectives, o Pl edited by Peter G Welling and Francis L. S Tse s - 34. Clinical Drug Trials and Tribulations, edited by Allen E Cato e gi 35. Transdermal Drug Delivery Developmental Issues and Research Ini- olo tiatives, edited by Jonathan Hadgraft and Richard H Guy n 36 Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms, h c edited by James W McGmity e T d 37 Pharmaceutical Pelletization Technology, edited by Isaac Ghebre- o Sellassie o F 38. Good Laboratory Practice Regulations, edited by Allen F Hirsch f o 39. Nasal Systemic Drug Delivery, Yie W. Chien, Kenneth S E Su, and y sit Shyi-Feu Chang er 40 Modern Pharmaceutics Second Edition, Revised and Expanded, v ni edited by Gilbert S. Banker and Christopher T Rhodes U 41 Specialized Drug Delivery Systems: Manufacturing and Production [ y Technology, edited by Praveen Tyle b d 42 Topical Drug Delivery Formulations, edited by David W. Osborne and e d Anton H. Amann a o 43. Drug Stability. Principles and Practices, Jens T Carstensen nl w 44. Pharmaceutical Statistics: Practical and Clinical Applications, Second Do Edition, Revised and Expanded, Sanford Bolton 45. Biodegradable Polymers as Drug Delivery Systems, edited by Mark Chasin and Robert Langer 46. Prechnical Drug Disposition A Laboratory Handbook, Francis L S Tse and James J. Jaffe 47. HPLC in the Pharmaceutical Industry, edited by Godwin W. Fong and Stanley K. Lam 48. Pharmaceutical Bioequivalence, edited by Peter G. Welling, Francis L. S Tse, and Shrikant V. Dinghe Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved. 49 Pharmaceutical Dissolution Testing, Umesh V. Banakar 50 Novel Drug Delivery Systems' Second Edition, Revised and Expanded, Yie W, Chien 51 Managing the Clinical Drug Development Process, David M Coc- chetto and Ronald V. Ward/ 52. Good Manufacturing Practices for Pharmaceuticals: A Plan for Total Quality Control, Third Edition, edited by Sidney H Willig and James R. Stoker 53 Prodrugs. Topical and Ocular Drug Delivery, edited by Kenneth B. 4 Sloan 1 20 54. Pharmaceutical Inhalation Aerosol Technology, edited by Anthony J, ril Hickey Ap 55 Radiopharmaceuticals Chemistry and Pharmacology, edited by 1 Adrian D. Nunn 2 9 56 New Drug Approval Process. Second Edition, Revised and Expanded, 3 6: edited by Richard A. Guarino 0 57. Pharmaceutical Process Validation: Second Edition, Revised and Ex- ] at panded, edited by Ira R. Berry and Robert A. Nash div 58. Ophthalmic Drug Delivery Systems, edited byAshim K. Mitra v 59. Pharmaceutical Skin Penetration Enhancement, edited by Kenneth A o Pl Walters and Jonathan Hadgraft s - 60. Colonic Drug Absorption and Metabolism, edited by Peter R Bieck e gi 61. Pharmaceutical Particulate Carriers: Therapeutic Applications, edited o by Alain Rolland ol n 62. Drug Permeation Enhancement: Theory and Applications, edited by h c Dean S. Hsieh e T 63. Glycopeptide Antibiotics, edited by Ramaknshnan Nagarajan d o 64. Achieving Sterility in Medical and Pharmaceutical Products, Nigel A. o F Halls f o 65. Multiparticulate Oral Drug Delivery, edited by Isaac Ghebre-Sellassie y sit 66. Colloidal Drug Delivery Systems, edited by Jorg Kreuter er 67. Pharmacokmetics: Regulatory • Industrial • Academic Perspectives, v ni Second Edition, edited by Peter G. Welling and Francis L S Tse U 68. Drug Stability Principles and Practices, Second Edition, Revised and [ y Expanded, Jens T. Carstensen b d 69. Good Laboratory Practice Regulations. Second Edition, Revised and e d Expanded, edited by Sandy Weinberg a o 70. Physical Characterization of Pharmaceutical Solids, edited by Harry nl w G. Brittain Do 71. Pharmaceutical Powder Compaction Technology, edited by Goran Al- derborn and Christer Nystrom 72. Modern Pharmaceutics: Third Edition, Revised and Expanded, edited by Gilbert S. Banker and Christopher T. Rhodes 73. Microencapsulation: Methods and Industrial Applications, edited by Simon Benita 74. Oral Mucosal Drug Delivery, edited by Michael J. Rathbone 75. Clinical Research in Pharmaceutical Development, edited by Barry Bleidt and Michael Montagne Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved. 76 The Drug Development Process Increasing Efficiency and Cost Ef- fectiveness, edited by Peter G Welling, Louis Lasagna, and Umesh V Banakar 77. Microparticulate Systems for the Delivery of Proteins and Vaccines, edited by Smadar Cohen and Howard Bernstein 78. Good Manufacturing Practices for Pharmaceuticals: A Plan for Total Quality Control, Fourth Edition, Revised and Expanded, Sidney H Willig and James R Stoker 79 Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms. 4 1 Second Edition, Revised and Expanded, edited by James W 0 2 McGinity ril 80 Pharmaceutical Statistics Practical and Clinical Applications, Third p A Edition, Sanford Bolton 1 81 Handbook of Pharmaceutical Granulation Technology, edited by Dilip 2 9 M Parikh 3 6: 82 Biotechnology of Antibiotics: Second Edition, Revised and Expanded, 0 at edited by William R. Strohl ] 83. Mechanisms of Transdermal Drug Delivery, edited by Russell O Potts v di and Richard H. Guy ov 84 Pharmaceutical Enzymes, edited by Albert Lauwers and Simon Pl Scharpe - s 85 Development of Biopharmaceutical Parenteral Dosage Forms, edited e gi by John A Bontempo o ol 86 Pharmaceutical Project Management, edited by Tony Kennedy n 87 Drug Products for Clinical Trials. An International Guide to Formula- h ec tion « Production « Quality Control, edited by Donald C Monkhouse T d and Christopher I Rhodes o 88 Development and Formulation of Veterinary Dosage Forms Second o f F Edition, Revised and Expanded, edited by Gregory E Hardee and J. y o Desmond Baggot sit 89 Receptor-Based Drug Design, edited by Paul Left er 90. Automation and Validation of Information in Pharmaceutical Pro- v ni cessing, edited by Joseph F deSpautz U 91. Dermal Absorption and Toxicity Assessment, edited by Michael S [ y Roberts and Kenneth A Walters b d 92 Pharmaceutical Experimental Design, Gareth A Lewis, Didier e d Mathieu, and Roger Phan-Tan-Luu a nlo 93 Preparing for FDA Pre-Approval Inspections, edited by Martin D w Hynes III o D 94 Pharmaceutical Excipients. Characterization by IR, Raman, and NMR Spectroscopy, David E Bugay and W. Paul Findlay 95. Polymorphism in Pharmaceutical Solids, edited by Harry G. Bnttain 96. Freeze-Drymg/Lyophihzation of Pharmaceutical and Biological Prod- ucts, edited by Louis Rey and Joan C. May 97. Percutaneous Absorption: Drugs-Cosmetics-Mechanisms-Metho- dology, Third Edition, Revised and Expanded, edited by Robert L Bronaugh and Howard I Maibach Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved. 98. Bioadhesive Drug Delivery Systems: Fundamentals, Novel Ap- proaches, and Development, edited by Edith Mathiowitz, Donald E. Chickenng III, and Claus-Michael Lehr 99. Protein Formulation and Delivery, edited by Eugene J. McNally 100. New Drug Approval Process: Third Edition, The Global Challenge, edited by Richard A. Guarino 101. Peptide and Protein Drug Analysis, edited by Ronald E. Reid 102. Transport Processes in Pharmaceutical Systems, edited by Gordon L Amidon, Ping I. Lee, and Elizabeth M. Topp 4 103. Excipient Toxicity and Safety, edited by Myra L. Werner and Lois A. 1 0 Kotkoskie 2 ril 104. The Clinical Audit in Pharmaceutical Development, edited by Michael p R Hamrell A 1 105. Pharmaceutical Emulsions and Suspensions, edited by Francoise 2 9 Nielloud and Gilberte Marti-Mestres 3 106. Oral Drug Absorption: Prediction and Assessment, edited by Jennifer B. 6: 0 Dressman and Hans Lennemas at 107. Drug Stability. Principles and Practices, Third Edition, Revised and ] v Expanded, edited by Jens T. Carstensen and C. T. Rhodes di v 108. Containment in the Pharmaceutical Industry, edited by James P. o Pl Wood - 109. Good Manufacturing Practices for Pharmaceuticals. A Plan for Total s gie Quality Control from Manufacturer to Consumer, Fifth Edition, Revised o and Expanded, Sidney H. Willig ol n 110. Advanced Pharmaceutical Solids, Jens T. Carstensen h c 111. Endotoxms: Pyrogens, LAL Testing, and Depyrogenation, Second e T Edition, Revised and Expanded, Kevin L Williams d o 112. Pharmaceutical Process Engineering, Anthony J. Hickey and David o F Ganderton of 113. Pharmacogenomics, edited by Werner Kalow, Urs A. Meyer, and Ra- rsity 114. cHhaenl dFb.o Tokyn doaf leDrug Screening, edited by Ramaknshna Seethala and e niv Prabhavathi B. Fernandes U 115. Drug Targeting Technology: Physical • Chemical • Biological Methods, [ y edited by Hans Schreier b d 116 Drug-Drug Interactions, edited by A. David Rodngues de 117 Handbook of Pharmaceutical Analysis, edited by Lena Ohannesian a o and Anthony J. Streeter wnl 118 Pharmaceutical Process Scale-Up, edited by Michael Levin o 119. Dermatological and Transdermal Formulations, edited by Kenneth A. D Walters 120. Clinical Drug Trials and Tribulations: Second Edition, Revised and Expanded, edited by Allen Cato, Lynda Sutton, and Allen Cato III 121. Modern Pharmaceutics: Fourth Edition, Revised and Expanded, ed;- ted by Gilbert S. Banker and Christopher T. Rhodes 122. Surfactants and Polymers in Drug Delivery, Martin Malmsten 123. Transdermal Drug Delivery: Second Edition, Revised and Expanded, edited by Richard H. Guy and Jonathan Hadgraft Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved. 124, Good Laboratory Practice Regulations' Second Edition, Revised and Expanded, edited by Sandy Weinberg 125 Parenteral Quality Control. Sterility, Pyrogen, Particulate, and Pack- age Integrity Testing: Third Edition, Revised and Expanded, Michael J. Akers, Daniel S. Lammore, and Dana Morton Guazzo 126. Modified-Release Drug Delivery Technology, edited by Michael J. Rathbone, Jonathan Hadgraft, and Michael S. Roberts 127 Simulation for Designing Clinical Trials: A Pharmacokinetic-Pharma- codynamic Modeling Perspective, edited by Hut C. Kimko and Ste- 4 phen B. Duffull 1 0 128. Affinity Capillary Electrophoresis in Pharmaceutics and Biopharma- 2 ril ceutics, edited by Remhard H H. Neubert and Hans-Hermann Rut- p tinger A 1 129. Pharmaceutical Process Validation. An International Third Edition, Re- 2 9 vised and Expanded, edited by Robert A. Nash and Alfred H. Wachter 6:3 130 Ophthalmic Drug Delivery Systems: Second Edition, Revised and Ex- 0 panded, edited by Ashim K. Mitra at 131 Pharmaceutical Gene Delivery Systems, edited by Alain Rolland and ] v Sean M Sullivan di v 132. Biomarkers in Clinical Drug Development, edited by John C Bloom o Pl and Robert A Dean s - 133 Pharmaceutical Extrusion Technology, edited by Isaac Ghebre- gie Sellassie and Charles Martin o ol n h ec ADDITIONAL VOLUMES IN PREPARATIOIS T d o Pharmaceutical Inhalation Aerosol Technology Second Edition, Re- o F vised and Expanded, edited by Anthony J Hickey f o y sit Pharmaceutical Compliance, edited by Carmen Medina r e niv Pharmaceutical Statistics: Practical and Clinical Applications, Fourth U Edition, Sanford Bolton and Charles Bon [ y b d e d a o nl w o D Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved. 4 1 0 Preface 2 ril p A 1 2 9 3 6: 0 at ] v di v o Pl Extrusion is a process in which materials are mixed intimately under - s controlledconditionsoftemperature,shear,andpressuretogenerateavariety e gi of in-process and finished products using pieces of equipment collectively o ol known as extruders. Most of the early applications of this technology were n ch limitedto industrial processes that ranged from compaction ofclayand straw e T tothemasticationofrubber andplastics.Prominentinitsabsencethroughout d o this period was the application of extrusion in the development and manu- o F facture of pharmaceutical products. As a result, until recently, the pharma- f o ceutical industry contributed very little to the technological advances made y sit eitherinthe improvementof existing extrusion equipment or inthe design of er specialized extruders that satisfy its highly regulated sphere of operation. v ni However, as soon as work started on the applicability of the technology in U [ pharmaceutical dosage from development, it became apparent that extrusion y b processes not only improve the efficiency of pharmaceutical manufacturing ed processes, but also can significantly enhance the quality of manufactured d oa products owing to the mixing efficiency of extruders. The intent of this book nl is, therefore, to provide pharmaceutical scientists and technologies with basic w o principlesandfundamentalsofextrusiontechnologyandadetaileddescription D of the practical applications of extrusion processes. Chapter 1 provides a historical overview of extruders and extrusion technology, and describes the evolutionary development of the technology in an attempt to address the processing needs of the time. Early patents that formed the basis for the widespread use of the technology are highlighted. Extrusion design features that are common to general industrial applications, Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.