Lachman Vol2

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art of Citation[PU]Marcel Dekker, Inc.[/PU][DP]1992[/DP]End of Citation

title : Pharmaceutical Dosage Forms. Vol. 2: Parenteral Medication

author : Avis, Kenneth E.

publisher :

isbn10 | asin : 0824787714

print isbn13 : 9780824787714

ebook isbn13 : 9780585267005

language :

subject

publication date :

lcc :

ddc :

subject :

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P

Pharmaceutical Dosage Forms:Parenteral Medications Volume 2

Second Edition, Revised and Expanded

Edited byKenneth E. Avis

The University of TennesseeMemphis, Tennessee

Herbert A. LiebermanH.H. Lieberman Associates, Inc.

Consultant Services

Livingston, New Jersey

Leon LachmanLachman Consultant Services

Westbury, New York


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ibrary of Congress CataloginginPublication Data

harmaceutical dosage forms, parenteral medications / edited byKenneth E. Avis, Herbert A. Lieberman, and Leon Lachman. -- 2nd ed.,ev. and expanded. cm.

ncludes bibliographical references and index.SBN 0-8247-8576-2 (v. 1 : alk. paper) Parenteral solutions. 2. Pharmaceutical technology. I. Avis,

Kenneth E. II. Lieberman, Herbert A.I. Lachman, Leon.

DNLM: 1. Infusions, Parenteral. 2. Technology, Pharmaceutical.WB 354 P536]

S201.P37P48 199215'. 19--dc20NLM/DLC

or Library of Congress 91 -38063CIP

his book is printed on acid-free paper.

opyright 1992 by MARCEL DEKKER, INC. All Rights Reserved

Neither this book nor any part may be reproduced or transmitted in any formr by any means, electronic or mechanical, including photocopying, microfilming,nd recording, or by any information storage and retrieval system,

without permission in writing from the publisher.

MARCEL DEKKER, INC.70 Madison Avenue, New York, New York 10016

urrent printing (last digit):0 9 8 7 6 5 4 3

RINTED IN THE UNITED STATES OF AMERICA


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reface

Volume 2 of the first edition of our two-volume treatise on parenterals was published in 1986. In keeping with theditors' philosophy to update and adequately cover new subject matter, this second volume is now being published asart of a three-volume second edition of the series.

Volume 1 in the second edition is devoted to parenteral drug history, administration, routes, precautions, problems,iopharmaceutics, preformulations, small and large volume parenteral formulations, peptide and protein injectables,erile diagnostics, different types of parenteral primary packages and closures, and, finally, parenteral products inospital and home care. Volume 2 describes processing small and large volume parenterals, freeze drying, the designparenteral and a biopharmaceutical facility, personnel practices and training, environmental control elements in

manufacturing, industrial sterilization, as well as an enlightening coverage of the therapeutics, types of drugs, andormulation principles for ophthalmic preparations. The final and third volume in this series covers quality assuranceecords and reports, particulate matter, validations, federal regulations, the audit process, regulatory considerations ather aspects of medical devices, including design, manufacture, and quality assurance.

he editors have consistently guided the contributors to cover each subject with the intent of teaching at the level of tndergraduate, as well as the graduate student in the pharmaceutical sciences. To accomplish this goal, the writers hao assume the readers to have little knowledge of the subject matter and then build upon the more basic conceptsresented to reach the more learned and graduate level readers. Further, the materials presented in this series arentended to benefit the technical readers with the specific information required to guide professionals practicingndustrial or pharmaceutical pharmacy, to assist personnel involved in the design and manufacture of sterile products

well as to instruct lawyers and legislators concerned with all types of sterile products.


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All of the first-edition chapters included in this volume have been updated, and additional topics are included in eachevised chapter to more fully cover the changes in the subject matter since the publication of the first edition. Also, nhapters have been added.

hapter 1 on the processing of small volume parenterals, has been expanded to include several types of biologicroducts, including biotechnology-based preparations such as vaccines and monoclonal antibodies. There is a discusn preparing liposomal products, as well as a brief description concerning the manufacture of ophthalmic dosage forhe use of form, fill, and seal equipment for small volume parenterals is described in detail with several diagrams anlustrations included to help provide additional clarity to this subject. Many of the tables have been revised and the lf references updated. The chapter is designed to provide all the necessary details for setting up and running a state-ohe-art small volume parenteral facility.

n Chapter 2, the manufacturing processes describing large volume parenterals, has been considerably expandedompared with the presentation given in the first edition. Recent developments in the technology of parenteral fluidrocessing, the latest regulatory requirements, packaging (including currently employed materials), filling, sterilizatind filtration operations, as all of them pertain to large volume parenterals, are fully covered. In addition, the variousactors involved in manufacturing large volume parenterals are reinforced by offering practical examples of situationnd processes, both for improving production and quality assurance and control purposes.

hapter 3, "Freeze Drying: Principles and Practice," a new chapter in this edition, presents an overview of the scientnd engineering principles of freeze drying as it is relevant to the formulation and manufacture of freeze-driedarenteral products. Methodology for the characterization of freezing behavior is presented from the standpoint ofdentifying the maximum allowable product temperature during primary drying, that is, either a collapse temperatureamorphous solute) or a eutectic temperature (crystalline solute). Temperature and pressure measurement methods usn freeze drying are reviewed, followed by a discussion of process monitoring strategies. General equipment andonsiderations involved in designing a freeze drying system are discussed.

hapter 4 updates the various design considerations required for a parenteral production facility. Specific reference heen included to small specialized batch operations where localized and self-contained sterile enclosures may bepplicable, as for example, in the manufacture of lyophilized products. A discussion of clean-in-place (CIP) anderilizein-place (SIP) systems has been added. The HEPA filters topic has been updated and expanded in accordanc

with the current federal and Institute of Environmental Science standards. Laminar flow rooms with an illustration,eparate gowning and degowning areas, various safety, environmental, hazardous material control, energy conservatnd building code issues have been reviewed and revised to reflect current pharmaceutical practices.

hapter 5, which is new, describes the design of biopharmaceutical manufacturing facilities, concentrating on thehysical layout, with particular consideration for the planning and regulatory issues that need to be addressed.

Government regulatory maters, NIH guidelines, and FDA Good Manufacturing Practices as they pertain to themanufacture of biopharmaceutical products are discussed. The role of validation in the


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lanning process is presented along with a description of the design of the equipment outlay. This chapter highlightsifferences in planning for a biopharmaceutical manufacturing facility as compared with the design of aseptic facilitior parenteral products.

No text concerned with the manufacture of sterile products would be complete without a description of "Personnel: TKey Factor in Clean Room Operations," Chapter 6 of this text. The production personnel and the garments they wearwhen processing sterile preparations can play a significant role in the risk of contaminating these products in themanufacturing operations. To minimize this source of contamination, the chapter has provided a description of theoncepts of barrier technology and a lengthy discussion on the design of clean room uniforms, fabrics currentlyrescribed, tests used to evaluate fabrics, and the effects of laundering on garment permeability. Several types of facoverings worn by clean room operators are also described. Hand protection from microbial contamination and varioand washing techniques utilized by employees working in aseptic areas are discussed. Overall contents of a trainingrogram for clean room operators, as well as a section on management philosophy and their commitment to regulatorompliance, are included in this chapter.

hapter 7, "Environmental Control in Parenteral Drug Manufacturing," has been rewritten to include more detailsegarding environmental monitoring, validation of airborne and surface contamination, and the implementation of aoutine monitoring program. This chapter discusses the hardware presently recommended for clean room constructio

nd air filtration and also includes current regulatory requirements on these subjects. New topics included in this chare cleaning, disinfection, and personnel cleanliness requirements needed to achieve adequate environmental conditior an aseptic manufacturing facility.

Industrial Sterilization: A Review of Current Principles and Practices," Chapter 8, describes many of the recentdvances that have been introduced in the health care industry. New concepts and principles relating to sterilityssurance techniques and procedures have been added in this edition. Among the new subjects described are alternato ethylene oxide sterilization (e.g., vapor phase hydrogen peroxide, chlorine dioxide, and peracetic acid), parametricelease, chemical sterility indicators, and continuous sterilizers. Coverage of all the key areas of sterilization technoloave been expanded and include radiation, installation/performance qualification and validation, as well as a discussioncerning the health effects of ethylene oxide as a sterilant.

ince ophthalmic preparations must be sterile, although not pyrogenfree, the editors have included in this series a ne

hapter, Chapter 9, "Development of Ophthalmic Formulations." Although the dosage form is not a parenteral, theechniques required for sterile formulation development are the same, and in other texts on sterile products, this topicot adequately covered. In this chapter, topical ophthalmic products are discussed, andunlike many other pharmacyextsthe emphasis is on the development of intraocular preparations, particularly irrigating solutions. Included in thishapter is a review of the anatomy of the eye and the pharmacologic/therapeutic categories of drugs used inphthalmology practice. It also includes a flow chart with model formulations for the development of ophthalmicreparations. Manufacturing procedures for the preparation and packaging of ophthalmic products are briefly describ


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he multiauthor approach taken in this volume, as well as the others in the series, provides the editors and readers wiontributors who are scholars knowledgeable as well as experienced in the subject matter of their chapters. No oneuthor can offer the detailed and learned treatise required to adequately cover such a variety of subjects included in tolume. The experts chosen in particular areas offer comprehensive knowledge at a level that will satisfy theequirements of both the novice and the highly experienced reader.

he contributing authors have worked hard to provide our readers with information needed to help them solve problen manufacturing all types of sterile parenteral, biologic, and ophthalmic products. We are extremely grateful for theme and effort each has given to prepare a chapter despite a busy work schedule. We hope that the extensive coveragf the subject matter in this book will facilitate the reader's tasks, as well as elevate the present technology practiced eveloping and manufacturing parenteral, biologic, and ophthalmic products.

KENNETH E. AVISHERBERT A. LIEBERMANLEON LACHMAN


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ontents

Preface iii

Contributors ix

Contents of Pharmaceutical Dosage Forms: Parenteral Medications, Volumes 1 and 3 xi

Contents of Pharmaceutical Dosage Forms: Tablets, Volumes 1-3 xiii

Contents of Pharmaceutical Dosage Forms: Disperse Systems, Volumes 1 and 2 xv

. The Processing of Small Volume Parenterals and Related Sterile ProductsRichard J. Harwood, Joel Benton Portnoff, And Edward William Sunbery

1

. Factors Involved in Manufacturing Large Volume ParenteralsMichael J. Groves, Karen L. Malik, And Nicholas J. Kartinos

93

. Freeze Drying: Principles and PracticeSteven L. Nail And Larry A. Gatlin

163

. Design Considerations for a Parenteral Production FacilityA. Michael Keller And Gary L. Hoffman

235

. Biopharmaceutical Manufacturing Facility DesignRobert Del Ciello

317

. Personnel: The Key Factor in Clean Room OperationsCecelia J. Luna

367

. Environmental Control in Parenteral DrugManufacturingFranco Devecchi

411


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. Industrial Sterilization: A Review of Current Principles and PracticesFrank J. Marino

473

. Development of Ophthalmic Formulations

Krishna M. Bapatla And 0. J. Lorenzetti

541

ndex 583


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ontributors

Krishna M. Bapatla, Ph.D. Associate Director, Project Management, Alcon Laboratories, Inc., Fort Worth, Texas

obert Del Ciello, P.E. Director, Pharmaceutical and Biotechnology Operations, Quasar Engineering, Inc., PrincetonNew Jersey

ranco DeVecchi Chairman of the Board, Veco International, Inc., Farmington Hills, Michigan

arry A. Gatlin, Ph.D. Section Head, Parenteral and Enteral Liquid Product Development, Pharmaceutical Research evelopment, Glaxo Research Institute, Research Triangle Park, North Carolina

Michael J. Groves, Ph.D. Director, Institute for Tuberculosis Research, College of Pharmacy, University of Illinois ahicago, Chicago, Illinois

ichard J. Harwood, Ph.D, Director, Technical Planning, Strategic Management Operations, Bristol-Myers Squibb,rinceton, New Jersey

Gary L. Hoffman Merck Pharmaceutical Manufacturing Division, West Point, Pennsylvania

Nicholas J. Kartinos, Ph.D. Consultant, Chicago, Illinois

A. Michael Keller, P.E. Project Manager, Budlong & Associates, Agoura Hills, California

. J. Lorenzetti, Ph.D. Senior Director, Therapeutic Research, Research and Development, Alcon Laboratories, Inc.,ort Worth, Texas

ecelia J. Luna Validation Project Manager, Validation Services, United Engineers & Constructors, Philadelphia,ennsylvania


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Karen L. Malik Baxter Healthcare Laboratories, Inc., Round Lake, Illinois

rank J. Marino, M.S. Corporate Consultant, Microbiology, Corporate Quality Assurance, Abbott Laboratories, Northicago, Illinois

teven L. Nail, Ph.D. Associate Professor, Industrial and Physical Pharmacy, Purdue University, West Lafayette,ndiana

oel Benton Portnoff Executive Director of Development, Analytical and Pharmaceutical Research and Developmenhe Liposome Company, Inc., Princeton, New Jersey

dward William Sunbery, RPh. Manager, Technical Services, WarnerLambert Company, Inc., Lititz, Pennsylvania


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ontents of Pharmaceutical Dosage Forms:arenteral Medications, Second Edition, Revised and Expanded, Volumes 1 and 3

Volume 1

The Parenteral Dosage Form and Its Historical Development, Kenneth E. Avis

Parenteral Drug Administration: Routes, Precautions, Problems, Complications, and Drug Delivery Systems,RichDuma, Michael J. Akers, and Salvatore J. Turco

Biopharmaceutics of Injectable Medications, Sol Motola

Preformulation Research of Parenteral Medications, Sol Motola and Shreeram N. Agharkar

Formulation of Small Volume Parenterals, Patrick P. DeLuca and James C. Boylan

Formulation of Large Volume Parenterals,Levit J. Demorest and Jeffrey G. Hamilton

Parenteral Products of Peptides and Proteins, Yu-Chang John Wang

Sterile Diagnostics,Leif E. Olsen

Glass Containers for Parenterals,R. Paul Abendroth and Robert N. Clark

0. Use of Plastics for Parenteral Packaging,John M. Anes, Robert S. Nase, and Charles H. White

1. Elastomeric Closures for Parenterals,Edward J. Smith and Robert J. Nash

2. Parenteral Products in Hospital and Home Care Pharmacy Practice,John W. Levchuk


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Volume 3

Quality Assuranceamir A. Hanna

Records and ReportsDavid C. Fry

Particulate Matteratrick P. DeLuca and Julius Z. Knapp

Validation of Sterilization Processes and Sterile Productsames Agalloco and James Akers

Federal Regulation of Parenteralserry E. Munson, Jonas L. Bassen, and Bernard T. Loftus

Systematic Audits of Parenteral Good Manufacturing Practicesonald F. Tetzlaff

Medical Devices: Design, Manufacture, and Quality ControlDavid H. Wayt

Quality Assurance for Medical Devicesarl W. Bruch

Regulatory and GMP Considerations for Medical Devicesarry R. Pilot


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ontents of Pharmaceutical Dosage Forms:ablets, Second Edition, Revised and Expanded, Volumes 1-3

dited by Herbert A. Lieberman, Leon Lachman, and Joseph B. Schwartz

Volume 1

Preformulation Testing,Deodatt A. Wadke, Abu T. M. Serajuddin, and Harold Jacobson

Tablet Formulation and Design, George J. Baley, Vincent E. McCurdy, Garnet E. Peck, and Gilbert S. Banker

Compressed Tablets by Wet Granulation, Fred J. Bandelin

Compressed Tablets by Direct Compression,Ralph F. Shangraw

Compression-Coated and Layer Tablets, William C. Gunsel and Robert G. Dusel

Effervescent Tablets,Raymond Mohrle

Special Tablets,James W. Conine and Michael J. Pikal

Chewable Tablets,Robert W. Mendes, Aloysius O. Anaebonam, and Jahan B. Daruwala

Medicated Lozenges,David Peters


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Volume 2

Mixing,ussell J. Lantz, Jr. and Joseph B. Schwartz

Drying,Kurt G. Van Scoik,Michael A. Zoglio, and Jens T. Carstensen

Size Reduction,ussell J. Lantz, Jr.

Compression,ugene L. Parrott

Granulation and Tablet Characteristics,oger E. Gordon, Dale E. Fonner, Neil R. Anderson, and Gilbert S. Banker

Bioavailability in Tablet Technology,alomon A. Stavchanskv, James W. McGinity, and Alfred Martin

Pharmaceutical Tablet Compression Tooling,Glen Ebey and George F. Loeffler

Volume 3

Principles of Improved Tablet Production System Design,Garnet E. Peck, Neil R. Anderson, and Gilbert S. Banker

Pan Coating of Tablets and Granules,tuart C. Porter

Particle-Coating Methods,Dale E. Wurster

Sustained Drug Release from Tablets and Particles through Coating,ong-Kun Chang and Joseph R. Robinson

Pharmaceutical Pilot Plant,harles I. Jarowski

Tablet Production,obert Connelly, Frank Berstler, and David Coffin-Beach

Stability/Kinetics,amir A. Hanna

Quality Assurance,amir A. Hanna


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ontents of Pharmaceutical Dosage Forms:isperse Systems, Volumes 1 and 2

dited by Herbert A. Lieberman, Martin M. Rieger, and Gilbert S. Banker

Volume 1

Introduction,Norman Weiner

Theory of Suspensions,Michael J. Falkowicz

Theory of Emulsions,tig E. Friberg, Lisa B. Goldsmith, and Martha L. Hilton

Theory of Colloids,ohn Vanderhoff and Mohamed S. El-Aasser

Pharmaceutical Suspensions,obert A. Nash

Pharmaceutical Emulsions,ernard Idson

Specialized Pharmaceutical Emulsions,Morton Rosoff

Surfactants,Martin M. Rieger

Rheology of Dispersed Systems,Donald E. Deem

0. Experimental Design, Modeling, and Optimization Strategies for Product and Process Development,obert M. Franz, Jeffrey E. Browne, and Allen R. Lewis

Volume 2

A Practical Guide to Equipment Selection and Operating Techniquesoy R. Scott

Preservation of Dispersed SystemsHarun Takruri and Claude B. Anger


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Bioavailability of Disperse Dosage Formsonald D. Schoenwald and Douglas R. Flanagan

Viscosity-Imparting Agents in Disperse Systemsoel L. Zatz, Joseph J. Berry, and Daniel A. Alderman

Antacids and Clay Productsichard J. Harwood, Joseph R. Luber, and Edward W. Sunbery

Oral Aqueous Suspensionslyde M. Ofner III, Roger L. Schnaare, and Joseph B. Schwartz

Topical SuspensionsHridaya N.Bhargava and Daniel W.Nicolai

Reconstitutable Suspensionslyde M. Ofner III, Roger L. Schaare, and Joseph B. Schwartz

Emulsions and Microemulsionsawrence H. Block

0. Injectable Emulsions and Suspensionsoe Bruce Boyett and Craig William Davis

1. Aerosol Suspensions and Emulsionsohn J. Sciarra and Anthony J. Cutie

2. Ophthalmic Ointment SuspensionsKrishna M. Bapatla and Gerald Hecht

3. Gelsoel L. Zatz and Gregory P. Kushla

4. ToothpastesDavid Garlen

5. Suppository Development and Production MarionGold

6. LiposomesMohammad Riaz, Norman Weiner, and Frank Martin

7. Drug Regulatory Affairs

ohn P. Tomaszewski

8. Quality Assuranceamir A. Hanna


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7/24/2019 L

Documents

Lachman Vol2