iD uw is
`
`alse y) A
`
`|aDr--M&S il
`Piuieinreecriitalceall
`Cene-Cinees
`
`orinm Cun
`
`PNONve
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1013, p. 1 of 408
`
`

`

`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1013, p. 2 of 408
`
`

`

`
`
`ALFONSO R GENNARG
`Editor, and Chairman
`of the Editorial Boord
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1013, p. 3 of 408
`
`

`

`
`
`
`
`1990
`
`MACK PUBLISHING COMPANY
`
`Easton, Pennsylvania 18042
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1013, p. 4 of 408
`
`

`

`Isntered according to Act. of Congress, in the year 1885 by Joseph P Remington,
`in the Office of the Librarian of Congress, at Washington DC
`Copyright 1889, 1894, 1905, 1907, 1917, hy Joseph P Remington
`Copyright 1926, 1936, by Joseph P Remington Estate
`
`copyright 1948, 1951, by The Philadelphia Coltege of Phaxmnacy and Science
`Copyright © 1956, 1960, 1965, 1970, 1975, 1980, 1985, 1990, by ‘The Philadelphia College of
`Pharmacy and Science
`
`All Rights Reserved
`
`Library of Congress Catalog Card No, 60-53334
`ISBN 0-912734-04-8
`
`The use of structural formulas fram USAN and the USP Dictionary of Drug Names is by
`permission of The USP Convention. The Conventionis not responsible for any inaccuraey
`contained herein.
`
`Notice—This text is not intended to represent, narshall it be interpreted to be, the equivalent
`of or a substitute for the official United States Pharmocepeia (USP) and/or the National
`Formulary (NF).
`In the event of any difference or discrepancy between the currentofficial
`USPor NF standards of strength, quality, purity, packaging and labeling for drugs and
`representations of them herein, the context and effect of the official compendia shall
`prevail,
`
`Printed in the United States of America by the Mack Printing Company, Easton, Pennsyluania
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1013, p. 5 of 408
`
`

`

`Sa
`
`Remington’s Pharmaceutical Sciemees |, . a treofise on the theory
`and practice of the pharmaceutical sciences, with essential
`information about pharmaceutical and medicinal agents; also a guide
`fo the professional responsibilities of the pharmacist as the
`drug-information specialist of the health team... A textbook
`and reference work for pharmacists, physicians and other
`practitioners of the pharmaceutical and medicalsciences.
`
`EDITORS
`
`Alfonso R Gennaro, Chairman
`
`Thomas Medwick
`
`Grafton D Chase
`
`Ara Der Marderosian
`
`Stewart C Harvey
`
`Daniet A Hussar
`
`Edward G Rippie
`
`Joseph B Schwartz
`
`Ewart A Swinyard
`
`Gilbert L Zink
`
`AUTHORS
`
`The 109 chapters of this edition of Remington's Pharmaceutical
`Sciences were written by the editors, by members of the
`Editorial Board, and by other authors listed on pagesix to xi.
`
`Managing Editor
`
`Editorial Assistant
`
`John E Hoaver
`
`Bonnie Brigham Packer
`
`Director
`
`Allen Misher 14985-1990
`
`Eighteenth Edition — 1990
`
`Published in the 170th year of the
`PHILADELPHIA COLLEGE OF PHARMACY AND SCIENCE
`
`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1013, p. 6 of 408
`
`

`

`
`
`Remington Historical | Diographical Data
`
`The following is a record of the edifors and the dates of publication of successive editions of this book, prior to the f3th
`Edition known os Remington's Practice of Pharmacy and subsequently as Remington's Pharmaceutical Sclences.
`
`Firs¢ Edition, 7866
`Second Edision, 1889
`Third Edition, 1897
`Fourth Edition, 1905
`
`Fifth Edition, 1907
`Sbxth Edition, 1917
`
`Seventh Edition, 1928
`
`Editors
`E Fullerton Cook
`Charles H LaWall
`
`Eighth Edition, 1#36
`
`Edltors
`E Fuliertan Cook
`Chatles H LaWall
`
`Ninth Edition, 1948
`
`Tenth Edition, 1957
`
`Eleventh Edition, 7956
`
`Editors
`Eric W Martin
`E Fullerton Coak
`
`Twelfth Editlon, 1964
`
`Editors
`Eric W Martin
`E Fullerton Cook
`E Emersan Levallen
`Arthur Osol
`Linwood F Tice
`Clarence T Yan Mefer
`
`Joseph P Remington
`
`Joseph P Remington
`Assisted by
`E Fullerton Cook
`
`Associate Editors
`Ivor Griffith
`Adley D Nichals
`Arthur Osol
`
`Editors
`E Fullerton Cook
`Eric W Martin
`
`Editors
`E Fullerton Cook
`Eric W Martin
`
`Associate Editors
`E Emerson Levallen
`Arthur Osol
`Linwood F Tice
`Clarence T Van Meter
`
`Assistant to the Editors
`John E Hoover
`
`Thirteenth Editlon, 1965
`Edifor.in-Chief
`Erle W Martin
`Editors
`Grafton D Chase
`Herald & Cox
`Richard A Deno
`Alfonso A Gennaro
`Stewart C Harvey
`
`Fourteenth Editlan, 1970
`Choirmon, Editorial Board
`Arthur Osol
`Editors
`Grafton D Chase
`Richard A Deno
`Alfonso R Gennaro
`Melvin R Gibson
`Stewart C Harvey
`Fifteenth Edition, 1975
`Chairman, Editorlal Board
`Arthur Osol
`Editors
`John T Anderson
`Cecil L Bendush
`Grafton D Chase
`Alfonse A Gennaro
`Malvin R Gibson
`
`Sixteenth Edition, 1960
`Chairman, Editorial Doard
`Arthur Osol
`Editors
`Grafton D Chase
`Alfonso R Gennaro
`Melvin R Gibson
`
`€ Boyd Granberg
`Stewart C Harvey
`
`Seventeenth Edition, 1985
`Chairman, Editorial Board
`Alfonso & Gennaro
`Editors
`Grafton D Chase
`Ara Der Marderosian
`Stewart Harvey
`Daniel A Hussar
`Thomas Medwick
`
`Managing Editor
`John E Hoover
`
`Robert E King
`E Emerson Leuaillen
`Arthur Oso
`Ewart A Swinyard
`Clarence T Yan Meter
`
`Managing Editor
`John E Hoover
`
`Robert E King
`Alfred N Martin
`Ewart A Swinyard
`Clarence T Van Meter
`Bernard Witlin
`
`Managing Editor
`John E Hoover
`
`C Boyd Granberg
`Stewart C Harvey
`Robert E King
`Alfred N Martin
`Ewart A Swinyard
`
`Robert E King
`Alfred N Martin
`Ewart A Swinyard
`Gilbert L Zink
`
`Edward G Rippie
`Joseph BD Schwartz
`Ewart A Swinyard
`Glibert | Zink
`
`vill
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1013, p. 7 of 408
`
`

`

`
`
`Editorial Board Members and Editors
`
`Alfonso A Gennaro, PhD / Philadelphia College of Pharmacy and Science —Professor of
`Chemistry. Chalrman of the Editorial Board and Editor. Remingfon's Pharmaceutical
`Sciences. Caauthor, Chapter 22, Coeditor, Part 6, Pharmaceutical and Medicinal
`Agents.
`
`Grofton D Chose, PhD / Philadelphia College of Pharmacy and Science—~Emeritus Professor of
`Chemistry, Editor. Part 5, Radioisotopes in Pharmacy and Medicine. Author, Chapters
`32 and 33,
`
`Aro DerMorderosian, PhD / Philadelphia Callege of Pharmacy and Science—Professor of
`Pharmacognosy. Research Professor in Medicinal Chemistry. Editor, Part 1,
`Orientation. Author, Chapters 64, 74 and 96.
`
`Stewart C Horvey, PhD / University of Utoh School of Medicine—Professor of Pharmacology.
`Editorlal Board Member. Editor, Part 6, Pharmaceutical and Medicinal Agents.
`Author, Chapters 35, 38, 40, 43 to 47, 49, 64 ond 62. Coauthor, Chapters 36, 41 and
`30.
`
`Doniet A Hussar, PhD { Philadeiphia Coliege of Pharmacy and Sclence—Remington Professorof
`Pharmacy, Editorial Board Member. Editor, Part 9, Pharmaceutical Practice. Author,
`Chapters 100 and 102.
`
`Thomas Medwick, PhD / Rutgers University—Professor and Chairman, Department of
`Pharmaceutical Chemistry. Editorial Board member. Editor, Part 3, Pharmaceutical
`Chemistry, and Part 4, Testing and Analysis. Coauthor, Chapter 26.
`
`Edword G Ripple, PhD / University of Minnesota College of Pharmacy— Professor of
`Pharmaceutics, Editorial Board Member, Editor, Part 2, Pharmaceutics. Author,
`Chapter 12. Coauthor, Chapter 66.
`
`Joseph D Schwartz, PhD / Phliadelphia College of Pharmacy and Sclence-.LinwoodTice
`Professor of Pharmaceutics. Editorial Board Member. Editar, Part 6, Pharmaceutical
`
`Preparations and Thelr Manufacture. Coauthor, Chapters 68 and 89.
`
`Ewart A Swinyord, PhD / University of Utah—Prafessar Emeritus of Pharmacology, College of
`Pharmacy and School of Medicine. Edifarial Board member. Editor, Part 6,
`Pharmaceutical and Medicinal Agents. Author, Chapters 39, 42, 48, 53 to 60, 63, 65
`and 70, Coauthor, Chapter 66,
`
`Gilbert L Zink, PhD / Philadelphia College of Pharmacy and Sclence— Associate Professor of
`Biology, Editor, Part 7, Blojogical Products. Author, Chapter 74,
`
`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1013, p. 8 of 408
`
`

`

`
`
`Authors
`
`The following contributors to the Eighteenth Edition of Remingfon’s Pharmaceutical Sciences
`served as authors or coauthors, along with the editors and members of the Editorial Board.
`of the 10% chopters of this book.
`
`Wumed M Abdou, PhD / Vice President, Worldwide Pharmaceuti-
`cat Technical Operations, 2 R Squibb & Sons, Inc; Author of
`Chapter 30, Instrumental Methods of Analysis and Chapter
`81, Dissolution.
`Anu B Amerson, PharmD / Professor, College of Piarmacy/Di-
`rector, Drug Information Center, Chandler Medical Center,
`University of Kentucky; Author of Chapter 103, Clinieal Drug
`Literature.
`Poward C Ausel, PhD / Professor of Pharmacy and Dean, College
`of Pharmacy, University of Georgia; Author of Chapter 101,
`The Preseription.
`Keuneth E Avis, DSe / @imeritus Professor, Pharmaceutics, Cal-
`lege of Pharmacy, University of Tennessee, Memphis; Author
`of Chapter 84, Parenteral Preparations.
`Leonard C Bailey, PhY) / Associate Professor of Pharmaceutical
`Chemistry, Rutgers University College of Pharmacy; Authorof
`Chapter 29, Chromatography,
`Lawrence H Block, PhD / Professor of Pharmaceutics, Duqnesne
`University School of Pharmacy; Author of Chapter 87, Medi-
`cated Applicatians.
`Joseph B Bogardus, PhD / Basic Pharmaceutics Research, Bris-
`tol-Myers Company; Coauthor of Chapter £8, Reaction Kinet-
`ies.
`Sanford Bolton, PhD / Chairman, Department of Pharmacy and
`Administrative Sciences, St John’s University; Author of Chap-
`ter 10, Statistics,
`John Bosso, PharmD / Professor of Clinical Pharmacy and Ad-
`junct Professor of Pediatrics, College of Pharmacy and School
`of Medicine, University of Utah, Coauthor of Chapter 34, Dis-
`eases: Manifestations and Pathophysiology.
`B Sue Brizuela, MS / Assistant Professor of Information Science,
`Head of Public Services, Joseph W England Library, Phijadel-
`phia College of Pharmacy and Science, Coauthor of Chapter7,
`Brug information,
`Dale B Christensen, PhD / Associate Professor, Department of
`Pharmacy Practice, School of Pharmacy, University of Wash-
`ington; Coauthor of Chapter 11, Computer Setence.
`Sebastian G Ciancio, DDS / Professor and Chairman, Depart-
`ment. of Periodontology, School of Dental Medicine, State Uni-
`versity of New York at Buffalo; Author of Chapter 109, Dental
`Services.
`Kenneth A Connors, PhD / Professor of Pharmaceutics, Schoo! of
`Pharmacy, University of Wisconsin; Author of Chapter 14,
`Complex Formation,
`Anthony J Cutie, PhD / Profeasor of Pharmaceutics, Arnold and
`Marie Schwartz College of Pharmacy and Health Sciences,
`Long Island University; Cosuthor of Chapter 92, Aerosols.
`Anthony RK DiSaute, PhD / Vice President, Drug Delivery Re-
`search and Development, The Upjohn Company; Author of
`Chapter 76, Bicavatlability and Bioequivalency Testing.
`Clarence A Discher,* PhD / Professor Emeritua, Rutgers Univer-
`sity; Authorof Chapter 21, Jnorganie Pharmaceutical Chemis-
`try.
`Clyde R Erskine, Jr, BSe / Vice President, Corporate Quality
`Audits and Services, SmithKline Beckman Corporation; Au-
`thor of Chapter 82, Quality Assurance and Control.
`Lorraine D Evans, BS, H(ASCP) / Clinical Pathology, Bristol-
`Myers Company; Coauthorof Chapter 28, Clinical Analysis.
`William E Fassett, BS, MBA / Assistant Professor, Departmentof
`PharmacyPractice, Schoo! of Pharmacy, University of Wash-
`ington; Coauthor of Chapter 11, Computer Sefence.
`Joseph L Fink IJI, BS(Pharm), JD / Assistant Dean and Profes-
`sor, College of Pharmacy, University of Kentueky; Coauthorof
`Chapter (07, Laws Governing Pharmacy.
`
`* Deceased
`
`Michael R Franklin, PhD / Professor of Pharmacology, College of
`Pharmacy and School of Medicine, University of Utah; Author
`of Chapter 52, Enzymes,
`Ruta Freimanis, BS, RPh / Associate Secretary, United States
`Adopted Names Council; Coauthor of Chapter 24, Drug No-
`menclature-~ United Stutes Adopted Names.
`James W Freston, MD, PhD / Professor and Chairman, Depart-
`ment of Medicine, University of Connecticut Health Center;
`Coauthor of Chapter34, Diseases: Manifestations and Patho-
`physiology.
`Robert L Giles, BA / Vice President and General Manager, Glenn
`Beall engineering Inc; Coauthor of Chapter80, Plastic Packag-
`ing Matertals.
`Yarold N Godwin, MS / Professor and Director of Pharmacy, The
`University of Kansas Medical Center: Author of Chapter 94,
`Institutional Patient Care,
`Frederick J Goldstein, PhD / Professor of Pharmacology, Phila-
`dolphia Colloge of Pharinacy and Science; Coauthor of Chapter
`69, Pharmacological Aspects of Substance Abuse.
`A Richard Goolkasian, BS, RPh / Director of Alumni and Profes-
`sional Affairs, Massachusetts College of Pharmacy and Allied
`Health Sciences; Author of Chapter 1, Scope.
`Gerald Hechi, PhD / Director Process Development, Alcon Lab-
`oratories; Coauthorof Chapter 86, Ophthalmic Preparations.
`Judith A esp, MS / Instructor in Information Science, Coordina-
`tor of Bibliographic Instruction, Joseph W FEengland Library,
`Philadelphia College of Pharmacy and Science; Coauthor of
`Chapter 7, Drug Information.
`Gregory J Higby, PhD / Director, AmericanInstitute of the Histo-
`ry of Pharmacy, Schooi of Pharmacy, University of Wisconsin-
`Madison; Author of Chapter 2, Evolution of Pharmacy.
`Andrew S Katocks, Jr, PhD / Senior Research Pharmacologisg,
`American Cyanainid Company, Medical Research Division;
`Coauthor of Chapter 27, Biological Testing.
`Calvin WU Knowlton, MDiv, RPh / Clinical Associate Professor of
`Pharmacy, Philadelphia College of Pharmacy and Science, Au-
`thor of Chapter4, The Practice of Community Pharmacy.
`Richard W Knueppel, RPh/ President, Knueppel Wome Health
`Care Center; Author of Chapter 104, Wealth Accessories.
`Barry B Kostenbauder, PhD / Associate Dean for Research, Col-
`lege of Pharmacy, University of Kentucky; Coauthor of Chap-
`ter 18, Renction Kinetics.
`Richard L Kronenthal, PhD / Director of Research, Ethicon inc;
`Author of Chapter 105, Surgical Supplies.
`Arthur d Lawrence, PhD, RPh / Office of the Assistant Secretary
`of Health, US Public Health Service; Author of Chapter 6,
`Pharmacists in Government,
`Eric J Lien, PhD / Professor of Pharmaey / Pharmaceutics and
`Biomedical Chemistry, School of Pharmacy, University of
`Southern California; Author of Chapter 13, Molecular Sérue-
`ture, Properties and States of Motter,
`Mark A Longer, PhD / MCR Research Fellaw, Department of
`Biological Sciences, University of Keele; Coauthor of Chapter
`91, Sustatned-Helease Drug Delivery Systems.
`Werner Lowenthal, PhD / Professor of Pharmacy and Pharma-
`ceutics and Professor of Educational Development and Plan-
`ning, School of Pharmacy, Medical Caliege of Virginia; Authar
`of Chapter9, Metrology and Calculation.
`Karen 2 Main, PhD / Physical Pharmacist, Pharmaceutical De-
`velopment Department, [CI Pharmaceuticals Group; Coauthor
`of Chapter 26, Analysis of Medicinals.
`Deane D Miller, PhD / Professor and Chairman, Division of Me-
`dicinal Chemistry and Pharmacognosy, College of Pharmacy,
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1013, p. 9 of 408
`
`

`

`
`
`The Ohio State University; Author of Chapter 25, Structure-
`Names Couneil; Conuthor of Chapter 24, Drug Nomenela-
`Actiity Reletionship and Drug Design.
`ture-—-United States Adopted Names.
`Michael Montagne, PhD / Associate Professor of Pharmacy Ad-
`Wangs Schott, PhD/Professor of Pharmaceutics and Colloid
`ministration, Philadelphia College of Pharmacy and Science;
`Chemistry, School of Pharmacy, Temple University, Coauthor
`Coauthor of Chapter 3, &thics and Authorof Chapter 99, Drug
`of Chapter 19, Disperse Systems and Author of Chapter 20,
`Education.
`/
`Rheology.
`John D Mullins, PhD / Consultant; Coauthor of Chapter 86, Oph-
`John J Sciarra, PhD / President, Retail Drug Institute / Professor
`thalmic Preparations.
`of Industrial Pharmacy, Arnold and Marie Schwartz College of
`Maven J Myers, PhD / Professor of Pharmacy Administration,
`Pharmacy and Health Sciences, Long Island University; Coau-
`Philadelphia College of Pharmacy and Science; Coauthor of
`thor of Chapter 92, Aerosols.
`Jokn BH Shinkai, PhD / Emeritus Professor of Pharmaceutical
`Chapter3, Ethics.
`JG Nairn, PhD / Professor of Pharmacy, Faculty of Pharmacy,
`Chemistry, Rutgers University, College of Pharmacy; Coauthor
`University of Toronto; Author of Chapter 83, Solations, Emual-
`of Chapter 22, Organic Pharmaceutical Chemistry.
`sions, Suspensions and Extracts.
`E Richard Shough, PhD/ Associate Dean and Professor, Univer-
`Paul J Niebergall, PhD / Professor of Pharmaceutical and Sci-
`sity of Oklahoma Wealth Sciences Center, College of Pharmacy;
`ences / Director, Pharmaceutical Development Center, Medi-
`Authorof Chapter 78, Aleryenic lextracts.
`cal University of South Carolina; Author of Chapter 17, Jonie
`Fredorick P Siege}, PhD / Professor of Pharmaceutics, Colloge of
`Solutions and Electrolytic Equilibria.
`Pharmacy, Universityof Hinois; Author of Chapter 79, Tonici-
`Rehert & O'Connor, PhD / Merck Frosst Canada, Inc; Coauthorof
`ty, Osmotieity, Osmalality and Osmolarity.
`Chapter BB, Pawders.
`Larry M Sisonsmeier, BS(Pharm), JD / Associate Dean and
`Melanie O'Neil} / Becton Dickinson & Company; Coauthor of
`Professor, College of Pharmacy, Washington State University;
`Coauthor of Chapter 107, Laws Governing Pharmacy.
`Chapter 78, Sterilization,
`Robert D Smyth, PhD / Vice President, Pharmaceutical Deyelop-
`Richard W Pecina, PhD / President, Richard W Pecina & Asso-
`ment, Bristol-Myers Company; Coauthor of Chapter 28, Clini-
`ciates; Coauthor of Chapter 80, Plastic Packaging Materials.
`cal Analysis.
`Garnet E Peck, PhD / Profesaor of Industrial Pharmacy/ Direetor
`of the Industrial Pharmacy Laboratory, Purdue University;
`Thomas C Snader, PharmD / Consultant Pharmacist; Author of
`Author of Chapter 77, Separation.
`Chapter 95, Long-Term Care Facilities.
`Theodore D Sckoloski, PhD / Professor of Pharmacy, College of
`G Briggs Phillips, PhD / Becton Dickinson & Company; Coauthor
`Pharmacy, The Ohia State University; Author of Chapter 16,
`of Chapter 78, Sterilization.
`Solutions and Phase Equilibria.
`Nicholas G Popovich, Phi / Associate Professor of Pharmacy
`Robert B Stewart, MS / Professor and Chairman, Department of
`Practice, School of Pharmacy and Pharmacal Sciences, Purdue
`Pharmacy Practice, College of Pharmacy, University of Flori-
`University; Author of Chapter 93, Ambulatory Patient Care.
`da: Author of Chapter 67, Adverse Drug Reactions.
`Stuart C Porter, PhD / Vice President, Research and Develop-
`James Swarbrick, DSc, PhD / Professor and Chairman, Division
`ment, Colorcon; Author of Chapter 90, Coating of Pharmaceu-
`of Pharmaceutics, School of Pharmacy, University of North
`teal Dosage Forms.
`Carolina at Chapel Hill; Coauthor of Chapter 19, Disperse
`Galen Radebangh, PhD/ Director of Pharmaceutics, Parke-Davis
`Pharmaceutical Research Division, Warner-Lambert Compa-
`Systems.
`Anthony R Temple, MD / Director, Regulatory and Modical Af-
`ny; Coauthor of Chapter 75, Preformulation.
`fairs, MeNeil Consumer Products Company / Adjunct Asso-
`Paul L Ranolli, PhD / Assistant Professor of Pharmacy Adminis-
`ciate Professor, Department of Pediatrics, University of Penn-
`tration, Philadelphia College of Pharmacy and Science; Author
`sylvania School of Medicine / Lecturer, Philadelphia College af
`of Chapter 98, Patient Communication,
`Pharmacy and Science; Authorof Chapter 106, Paison Control.
`Louis J Ravin, PhD / Department of Pharmaceutics, Research and
`Jehn P Tischio, PhD / Principle Scientist, Immunohiology Re-
`Development, Smith Kline & French Laboratories; Coauthorof
`search Institute; Author of Chapter 68, Pharmacogenetics.
`Chapter 74, Preformulation.
`Salvatore J Turco, PharmD / Professor of Pharmacy, Temple
`Jack W Reich, PhD / Vice President Regulatory Affairs, Gensia
`University School of Pharmacy; Authorof Chapter 85, Jntrace-
`Pharmaceuticals, Inc; Author of Chapter 8, Research.
`nous Admixiures.
`James W Richards, MBA / Professor of Pharmacy Administra-
`Elizabeth B Vadas, PhD / Merck Frosst Canada, Inc; Author of
`tion, College of Pharmacy, University of Michigan; Author of
`Chapter 81, Stability of Pharmacettical Products.
`Chapter 108, Community Pharmacy Economics and Manage-
`ment.
`Ernestine Vandorveen, PhD / National Institute on Drug Abuse,
`ADAMHA;Coauthor of Chapter 51, Vitamins and Other Nu-
`Jack Robbina, PhD / Director, Pharmacy Affairs, Schering Lah-
`trients,
`oratories; Author of Chapter 5, Oppertunities for Pharmacists
`John E Vanderveen, PhD / Division of Nutrition, Pood and Drug
`in the Pharmaceutical Industry.
`Administration; Coauthor of Chapter 51, Vitamins and Other
`Joseph R Robinson, PhD / Professor of Pharmacy, School of
`Nutrients.
`Pharmacy, University of Wisconain; Coauthor of Chapter91,
`Vincont § Venturella, PhD / Section Manager, Pharmaceutical
`Sustained-Release Drug Delivery Systems.
`Research, Anaqueal, Div of BOC; Author of Chapter 23, Natu-
`Frank Roia, PhD / Professor of Biology, Philadelphia College of
`ral Products,
`Pharmacy and Science; Author of Chapter 72, Immunizing
`Albert I Wertheimer, PhD / Professor and Director, Department
`Agents and Diagnostic Skin Antigens.
`of Graduate Studies in Social and Adininistrative Pharmacy,
`Douglas E Rollins, MD, PhD / Associate Professor of Medicine
`College of Pharmacy, University of Minnesota; Author of
`and Pharmacology, School of Medicine and College of Pharma-
`Chapter 97, The Patient: Behavioral Determinants.
`cy, University of Utah; Author of Chapter87, Clinical Pharma-
`cohkinetics,
`Timothy S Wiedmann, PhD / Avsistant Professor, College of
`Pharmacy, University of Minnesota; Author of Chapter 15,
`G Vietor Rosai, PhD / Vice Presidont of Academic Affairs / Pro-
`Thermodynamics.
`fessor of Pharmacology, Philadelphia College of Pharmacy and
`C Dean Withrow, PHD / Associnte Professor of Pharmacology,
`Science; Coauthor of Chapter 27, Biological Testing and Coau-
`School of Medicine, University of Utah; Coauthor of Chapter
`thor of Chapter 69,
`36, Basie Pharmacokinetics, Conuthor of Chapter 41, Cardio-
`Edward Rudnic, PhD / Director, Formulation Development,
`vascular Drugs and Coauthor of Chapter 50, Hormones.
`Scharing Research; Coauthor of Chapter 89, Oral Solid Dosage
`farms,
`George Zografi, PhD / Professor, School of Pharmacy, University
`of Wisconsin; Coauthor of Chapter 19, Disperse Systems.
`Donald O Schiffman, PhD/Secretary, United States Adopted
`xi
`
`
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1013, p. 10 of 408
`
`

`

`
`
`Preface to the First Edition
`
`The rapid and substantial progress made in Pharmacy
`within the last. decade has created a necessity for a work
`treating of the improved apparatus, the revised processes,
`and the recently introduced preparations of the age.
`The vast. advances made in theoretical and applied chem-
`istry and physics have muchto do with the development of
`pharmaceutical science, and these have been reflectedinall
`the revised editions of the Pharmacopoeias which have been
`recently published. When the autbor was elected in 1874 Lo
`the chair of Theory and Practice of Pharmacyin the Phila-
`delphia College of Pharmacy, the outlines of study which
`had heen socarefully prepared for the classes by his eminent
`predecessors, Professor William Procter, Ji, and Professor
`Jédward Parrish, were found to be not strictly in accord,
`either in their arrangementofthe subjects or in their method
`of treatment. Desiring to preserve the distinctive charac-
`teristics of each, an effort was ai once made to frame a
`system which should embody their valuable features, em-
`brace new subjects, andstill retain that harmonyof plan and
`proper sequence which are absolutely essential to the suc-
`cess of any system.
`Thestrictly alphabetical classification of subjects whichis
`now universally adopted by pharmacopoeias and dispensa-
`tories, although admirable in works of reference, presents an
`effectual stumbling hlock bo the acquisition of pharmaceuti-
`cai knowledge through systematic study; the vast accumula-
`tion of facts collected under each head being arranged lexi-
`caily, they necessarily have no connection with one another,
`and thus the saving of labor effected by considering similar
`groups together, and the value of the associationof kindred
`subjects, are lost to the student.
`In the method ofgrouping
`the suhjects which is herein adopted, the constant aim has
`been to arrange the latter in such a manner that the reader
`shall be gradually led from the consideration of elementary
`subjects to those which Involve more advanced knowledge,
`whilst the groups themselves are so placed as to follow one
`anotherin a natural sequence.
`The work is divided into six parts. Part I is devoted to
`detailed descriptions of apparatus and definitions and com-
`ments on general pharmaceutical processes.
`The Official Preparations alone are considered in Part II.
`Due weight. and prominenceare thus given to the Pharmaco-
`poeia, the National authority, which is now so thoroughly
`recognized.
`in order Lo suil the convenience of pharmacists whoprefer
`to weigh solids and measure liquids, the official formulas are
`expressed, in addition to parts by weight,
`in avoirdupois
`weight and apothecaries’ measure. These equivalents are
`
`printed in bald bype near the margin, and arranged so as to
`fit them for quick and accurate reference.
`Payt THtreats of Inorganic Chemical Substances. Prece-
`dence is of course givento official preparation inthese.
`‘The
`descriptions, solubilities, and tests for identity and impuri-
`ties of each substance axe systematically tabulated underits
`proper title.
`It is confidently believed that by this methad
`of arrangement the valuable descriptive features of the
`Pharmacopoeia will be more prominently developed, ready
`reference facilitated, andclose study of the details rendered
`easy. Each chemical operation is accompanied by equa-
`tions, whilst the reactionis, in addition, explained in words.
`The Carbon Compounds, or Organic Chemical Sub-
`stances, are considered in Part TV. These are naturally
`grouped according to the physical and medical properties of
`their principal constituents, beginning with simple bodies
`like cellulin, gum, efc, and progressing to the mast. highly
`organized alkaloids, ete.
`Part V is devoted to Extemporaneous Pharmacy. Care
`has been takento treat. of the practice which would be best
`adapted for the needs of the many pharmacists who conduct.
`operations upon a moderate scale, rather than for those of
`the few who manage verylarge establishments.
`Inthis, as
`well as in otherparts of the work, operations are illustrated
`which are conducted by manufacturing pharmacists.
`Part VI contains a formulary of Pharmaceutical Prepara-
`tions which have not. been recognized by the Pharmacopoeia.
`Therecipes selected are chiefly those which have heen here-
`tofore ratherdifficult of access to most pharmacists, yet such
`as are likely to be in request. Many private formulas are
`embraced in the collection; and such of the preparations of
`the old Pharmacopocias as have not been included in the
`new edition, but are still in use, have been inserted.
`In conclusion, the author ventures to express the hope
`that the work will prove an efficient help Lo the pharmaceu-
`tical student as weil as to the pharmacist and the physician.
`Although the labor has been mainly performed amidst. the
`harassing cares of active professional duties, and perfection
`is known to be unattainable, no pains have been spared to
`discover and correct errors and omissions in the text. The
`auLhor’s warmest acknowledgments, are tendered to Mr AB
`Taylor, Mr Joseph McCreery, and Mr George M Smith for
`their valuable assistance in revising the proof sheets, and to
`the latter especially for his work on the index. The outline
`illustrations, by Mr John Collins, were drawneither from the
`actual objects or from photographs taken by the author.
`
`Philadelphia, October, 1885
`
`JPR,
`
`xii
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1013, p. 11 of 408
`
`

`

`
`
`Preface to the Eighteenth Edition
`
`In anticipation of setting forth this Preface and priorto
`gathering thoughts on paper (or more accurately, the word
`processor|}, this Editor paused to reread the preface to the
`first edition of Remington, published in 1885. Since it ap-
`pears on the preceding page of this book it is recommended
`highly. The first paragraph would he just as suitable today
`as penned by Professor Remington 105 years ago.
`Bach decade transcends the previous one and the pharma-
`ceutical and health sciences are not laggards. Every revi-
`sion of Remington has encompassed new viewpoints, ideas,
`doctrines or principles which, perhaps, were inconceivable
`for the previous edition.
`It ia a tribute to the authors and
`editors that they have kept abreast of the burgeoning litera-
`ture in their respective fields of expertise.
`Change not withstanding, the organization of this edition
`is similar to its immediate predecessors, being divided into 9
`Parts, each subdivided into several chapters. Every chapter
`has been culled, revised and rewritten to update the material
`presented.
`Two new chapters are evident; Biotechnology and Drugs
`(Chapter 74) and Drug Education (Chapter 99).
`‘Three
`chapters of the previous edition, which embraced Interfacial
`and Particle Phenomena and Colloidal and Coarse Disper-
`sions have been winnowed and combined into a single chap-
`ter entitled, Disperse Systems (Chapter 19}.
`The current revision contains an additional] 21 pages. A
`large amount of space (about 19 pages) gleaned from the
`review and condensation process, coupled with the extra
`pages, have been devoted primarily to expanding the con-
`tents of Part 6, Pharmaceutical and Medicinal Agents and
`Part 9, Pharmaceutical Practice.
`Excessive duplication of text is the bane of any editor
`dealing with a multitude of authors. While some duplica-
`tion in the discussion of rudimentary concepts is beneficial,
`there has been a special effort to cross-reference and elimi-
`nate unnecessary repetition. Space is at such a premium
`that it is hoped the reader will not be offended by being
`diverted to a different section of the text in order to obtain
`supplementary information.
`Photographs which depicted the typical “black box” have
`been eliminated almost completely and replaced by line
`drawings or schematic diagrams whichare instructive rather
`than picturesque.
`Most of the drug monographs have been revamped not
`only as a meansof updating, but to gain a degree of uniformi-
`ty. All structural formulas are now in the standard USAN
`form. Duplication of chemical names has been minimized
`and theinclusion of trade names increased. No attempt has
`been made to ferret out every trade name by which a product
`is known, and only the most commonare mentioned. The
`standard format for the major monographs is: Official
`Name, chemical name (CAS---inverted), trade name(s) and
`manufacturer(s), structural formula, CAS (Chemical Ab-
`stracts System} registry number (in brackets), molecular
`formula and formula weight (Gin parenthesis). This is fol-
`lowed by the method of preparation (or a reference if the
`method is lengthy), physical description, solubility, uses,
`dose and dosage forma.
`The number of authors remains at 97, however, 36 new
`authors have joined as contributors to Remington. As the
`credentials of the new authors touch upon many arens of
`pharmacy, every section of the book has been invigorated by
`the incorporation of updated and fresh concepts.
`
`As one primarily responsible for the production of a com-
`prehensive text devoted to the acience and practice of phar-
`macy, the wisdom of Dr Eric Martin, editor of the 13th
`Kdition, in creating an Editorial Board to share the enor-
`mous burden, has been evident constantly. Fach of the
`sectioneditors labored diligently to complywith the logistics
`of maintaining a smooth flow of manuscripts and proofs.
`Also, each section editor doubled as an author or coauthorof
`one or more chapters.
`It would be remiss not to extend
`special mention to this groupof dedicated people.
`Four memhers of the [editorial Board are serving for the
`first time after having been authors for several editions. Dr
`Ava DerMaxderosianof PCP&S, Editorfor Part 1; Dr Daniel
`Wussar, also of PCP&S, Part $9; Dr Edward Rippie of the
`University of Minnesota, Part 2; and Dr Joseph Schwartz of
`PCP&S, Part 8. Bach of the new members literally “jumped
`into the fray,” gave much of their precious time and have
`become “blooded” membersof the staff.
`The stalwarts of the Editorial Board surviving the trihula-
`tions of one or more previous editions of this work demand
`singular attention. Dr Grafton Chase of PCP&Sfor Part5,
`Radioisotopes in Pharmacy & Medicine; Dr ‘Thomas Med-
`wick of Rutgers University for Part 3, Pharmaceutical
`Chemistry and Part 4, Testing and Analysis; and Dr Gilbert
`Zink of PCP&S for Part 7, Biological Products.
`‘Two dauntiless, prolific contributors claim special recogni-
`tion. Drs Stewart Harvey and Ewart Swinyard, both of the
`University of Utah, have served on the Editorial Board for
`twenty and twenty-five years respectively, They bear the
`burden of Part 6, Pharmaceutical & Medicinal Agents,
`which comprises overone-third of the book. Their diligence
`and meticulous attention to deta