Handbook of
`
`PHARMACEUTICAL
`
`EXCIPIEN TS
`
`
`
`Third Edition
`
`Edited by
`
`Arthur H. Kibbe, Ph.D.
`Professor and Chair
`
`Department of Pharmaceutical Sciences
`Wilkes University School of Pharmacy
`Wilkes-Barre, Pennsylvania
`
`,....®.§
`
`American Pharmaceutical Association
`
`Washington, D.C.
`
`(RP)
`
`Phurmuceulical Press
`
`London, United Kingdom
`
`Amgen Ex. 2005
`
`Complex Innovations v. Amgen
`
`|PR2016-00085
`
`Amgen Ex. 2005
`Complex Innovations v. Amgen
`IPR2016-00085
`
`

`
` Published by the American Pharmaceutical Association
`
`2215 Constitution Avenue NW, Washington, DC 20037-2985, USA
`www.aphanet.org
`and the Pharmaceutical Press
`1 Lambeth High Street, London SE1 7JN, UK
`www.pharmpress.com
`
`© 1986, 1994, 2000 American Pharmaceutical Association and Pharmaceutical Press
`
`First edition 1986
`Second edition 1994
`Third edition 2000
`
`Printed in the United States of America
`
`ISBN: 0-85369—38l-l (UK)
`ISBN: 0-917330-96—X (USA)
`
`Library of Congress Cataloging-in-Publication Data
`Handbook of pharmaceutical excipients / edited by Arthur H. Kibbe.--3rd ed.
`p.
`; cm.
`Includes bibliographical references and index.
`ISBN 0-917330-96—X
`
`1. Excipients--Handbooks, manuals, etc.
`Pharmaceutical Association.
`
`I. Kibbe, Arthur H. II. American
`
`[DNLM: 1. Excipients--Handbooks. QV 735 H236 2000]
`RS201.E87 H36 2000
`615'.l9--dc21
`
`A catalogue record for this book is available from the British Library.
`
`
`
`99-044554
`
`All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or
`by any means, without the prior written permission of the copyright holder. The publisher makes no representation, express or
`implied, with regard to the accuracy of the information contained in this book and cannot accept any legal responsibility or
`liability for any errors or omissions that may be made.
`
`Managing Editor: Melanie Segala
`Copyeditor:
`Paul Gottehrer
`Indexer:
`Lillian Rodberg
`Compositor:
`Roy Barnhill
`Cover Designer:
`Tim Kaage
`
`
`
`

`
`
`
`Contents
`
`Committees
`Contributors
`Additions to the Third Edition
`Related Substances
`Preface
`Acknowledgments
`Notice to Readers
`
`Selected Bibliography
`Abbreviations
`
`Units of Measurement
`
`Monographs
`Acacia
`Acesulfame Potassium
`Albumin
`Alcohol
`
`Alginic Acid
`Aliphatic Polyesters
`Alpha Tocopherol
`Ascorbic Acid
`Ascorbyl Palmitate
`Aspartame
`'
`Bentonite
`Benzalkonium Chloride
`Benzethonium Chloride
`Benzoic Acid
`
`Benzyl Alcohol
`Benzyl Benzoate
`Bronopol
`Butylated Hydroxyanisole
`Butylated Hydroxytoluene
`Butylparaben
`Calcium Carbonate
`Calcium Phosphate, Dibasic Anhydrous
`Calcium Phosphate, Dibasic Dihydrate
`Calcium Phosphate, Tribasic
`Calcium Stearate
`Calcium Sulfate
`Canola Oil
`Carbomer
`Carbon Dioxide
`
`Carboxymethylcellulose Calcium
`Carboxymethylcellulose Sodium
`Carrageenan
`Castor Oil, Hydrogenated
`Cellulose Acetate
`Cellulose Acetate Phthalate
`
`Cellulose, Microcrystalline
`Cellulose, Powdered
`Cellulose, Silicified Microcrystalline
`Cetostearyl Alcohol
`Cetrimide
`Cetyl Alcohol
`Chlorhexidine
`Chlorobutanol
`Chlorocresol
`Chlorodifluoroethane (HCFC)
`Chlorofluorocarbons (CFC)
`
`vii
`ix
`xii
`xiii
`xv
`xvii
`xviii
`xviii
`xix
`xx
`
`Cholesterol
`
`Citric Acid Monohydrate
`Colloidal Silicon Dioxide
`
`Coloring Agents
`Corn Oil
`Cottonseed Oil
`Cresol
`Croscarmellose Sodium
`
`Crospovidone
`Cyclodextrins
`Dextrates
`Dextrin
`Dextrose
`
`Dibutyl Sebacate
`Diethanolamine
`
`Diethyl Phthalate
`Difluoroethane (HFC)
`Dimethyl Ether
`Docusate Sodium
`Edetic Acid
`
`Ethylcellulose
`Ethyl Maltol
`Ethyl Oleate
`Ethylparaben
`Ethyl Vanillin
`Fructose
`Fumaric Acid
`Gelatin
`Glucose, Liquid
`Glycerin
`Glyceryl Monooleate
`Glyceryl Monostearate
`Glyceryl Palmitostearate
`Glycofurol
`Guar Gum
`
`Heptafluoropropane (HFC)
`Hydrocarbons (HC)
`Hydrochloric Acid
`Hydroxyethyl Cellulose
`Hydroxypropyl Cellulose
`Hydroxypropyl Cellulose, Low-substituted
`Hydroxypropyl Methylcellulose
`Hydroxypropyl Methylcellulose Phthalate
`Imidurea
`
`Isopropyl Alcohol
`Isopropyl Myristate
`Isopropyl Palmitate
`Kaolin
`Lactic Acid
`Lactitol
`Lactose
`Lanolin
`Lanolin Alcohols
`Lanolin, Hydrous
`Lecithin
`
`Magnesium Aluminum Silicate
`Magnesium Carbonate
`Magnesium Oxide
`Magnesium Stearate
`Magnesium Trisilicate
`
`138
`140
`143
`146
`154
`156
`158
`160
`163
`165
`169
`172
`175
`178
`180
`182
`184
`186
`188
`191
`195
`201
`203
`205
`208
`210
`213
`215
`218
`220
`223
`225
`228
`230
`232
`234
`236
`238
`240
`244
`249
`252
`256
`261
`263
`265
`267
`269
`272
`274
`276
`286
`288
`290
`292
`295
`299
`303
`305
`309
`
`

`
`
`
`vi Contents
`
`Malic Acid
`Maltitol
`Maltitol Solution
`Maltodextrin
`Maltol
`Maltose
`Mannitol
`
`Medium Chain Triglycerides
`Meglumine
`Menthol
`
`Methylcellulose
`Methylparaben
`Mineral Oil
`
`.
`Mineral Oil, Light
`Mineral Oil and Lanolin Alcohols
`Monoethanolamine
`
`Nitrogen
`Nitrous Oxide
`Oleic Acid
`
`I
`
`Paraffin
`Peanut Oil
`Petrolatum
`Petrolatum and Lanolin Alcohols
`Phenol
`
`Phenoxyethanol
`Phenylethyl Alcohol
`Phenylmercuric Acetate
`Phenylmercuric Borate
`Phenylmercuric Nitrate
`Polacrilin Potassium
`Poloxamer
`Polydextrose
`Polyethylene Glycol
`Polyethylene Oxide
`Polymethacrylates
`Polyoxyethylene Alkyl Ethers
`Polyoxyethylene Castor Oil Derivatives
`Polyoxyethylene Sorbitan Fatty Acid Esters
`Polyoxyethylene Stearates
`Polyvinyl Alcohol
`Potassium Chloride
`Potassium Citrate
`Potassium Sorbate
`Povidone
`
`Propylene Carbonate
`Propylene Glycol
`Propylene Glycol Alginate
`Propyl Gallate
`Propylparaben
`Saccharin
`Saccharin Sodium
`Sesame Oil
`Shellac
`Sodium Alginate
`
`311
`313
`315
`317
`320
`322
`324
`329
`332
`334
`336
`340
`345
`347
`349
`350
`352
`354
`356
`358
`360
`362
`365
`367
`370
`372
`374
`377
`379
`383
`386
`389
`392
`399
`401
`407
`412
`416
`420
`424
`426
`429
`431
`433
`440
`442
`445
`447
`450
`454
`457
`460
`462
`465
`
`Sodium Ascorbate
`Sodium Benzoate
`Sodium Bicarbonate
`Sodium Chloride
`Sodium Citrate Dihydrate
`Sodium Cyclamate
`Sodium Lauryl Sulfate
`Sodium Metabisulfite
`
`Sodium Phosphate, Dibasic
`Sodium Phosphate, Monobasic
`Sodium Propionate
`Sodium Starch Glycolate
`Sodium Stearyl Fumarate
`Sorbic Acid
`Sorbitan Esters (Sorbitan Fatty Acid Esters)
`Sorbitol
`
`Soybean Oil
`Starch
`
`Starch, Pregelatinized
`Starch, Sterilizable Maize
`Stearic Acid
`
`Stearyl Alcohol
`Sucrose
`
`Sugar, Compressible
`Sugar, Confectioner’s
`Sugar Spheres
`Suppository Bases, Hard Fat
`Talc
`Tartaric Acid
`Tetrafluoroethane (HFC)
`Thimerosal
`Titanium Dioxide
`Tragacanth
`Triacetin
`Triethanolamine
`
`Triethyl Citrate
`Vanillin
`
`Vegetable Oil, Hydrogenated, Type I
`Water
`
`Wax, Anionic Emulsifying
`Wax, Carnauba
`Wax, Cetyl Esters
`Wax, Microcrystalline
`Wax, Nonionic Emulsifying
`Wax, White
`Wax, Yellow
`Xanthan Gum
`
`Xylitol
`Zein
`Zinc Stearate
`
`Appendix I: Suppliers’ Directory
`Appendix II: HPE Laboratory Methods
`Index
`
`468
`471
`474
`478
`482
`485
`487
`490
`493
`496
`498
`501
`505
`508
`511
`515
`519
`522
`528
`31
`534
`537
`539
`544
`546
`548
`550
`555
`558
`560
`562
`565
`568
`570
`572
`574
`576
`578
`580
`585
`587
`589
`591
`593
`595
`597
`599
`602
`606
`608
`
`611
`641
`645
`
`

`
`
`
`Preface
`
`Pharmaceutical dosage forms contain both active ingredients
`and inactive materials called excipients. The behavior of the
`dosage form is dependent on process variables and the inter-
`relationship between the various excipients and their impact
`on the active ingredient. Suppliers of excipients have devel-
`oped novel excipient mixtures and new physical forms of ex-
`cipients, which give them improved characteristics. In addition,
`the international nature of the pharmaceutical industry and its
`suppliers demands that formulators throughout the world have
`as much information as possible about the chemical and phys-
`ical nature of excipients and combinations of excipients. For-
`mulators are also concerned about the effect of the finished
`product on the patient it is intended to treat. Therefore, they
`are concerned about general and specific toxic effects of the
`excipients, allergic reactions to excipients, disease-specific in-
`tolerance to excipients and interactions between the excipient
`and the active ingredient. In addition, formulators need to be
`aware of the potential environmental impact of the use of ex-
`cipients. Lastly, the effect of regulatory change associated with
`harmonization is also a concern of the professional formulator.
`
`The Handbook of Pharmaceutical Excipients is a joint publica-
`tion of the American Pharmaceutical Association and the Royal
`Pharmaceutical Society of Great Britain. The Handbook of
`Pharmaceutical Excipients, originally published in 1986, was
`the first English-language publication to comprehensively and
`systematically describe the chemical and physical properties of
`pharmaceutical excipients. The first edition contained 145 mono-
`graphs, and the second contained 203. The present edition con-
`tains 210 monographs authored by experts in pharmaceutical
`formulation or excipient manufacture from around the world.
`This edition also contains the results of extensive laboratory
`testing carried out over the last two years in laboratories in
`Great Britain and the United States. Some data developed by
`the first edition’s laboratory project are retained. It is clearly
`noted as such in the monographs. The new data generated for
`this edition should help the formulator in the selection of ap-
`propriate excipients for various dosage forms. A major devel-
`opment since the publication of the last edition of the Handbook
`has been the trend towards global pharmaceutical harmonization.
`To reflect this, where appropriate, more detailed information on
`excipients used in Japan has been included in this edition. Ad-
`ditionally the index has been revised and expanded and the sup-
`pliers’ directory has been completely updated.
`The Handbook of Pharmaceutical Excipients collects in a sys-
`tcmatic and uniform manner essential data on the physical prop-
`erties of excipients such as: boiling point, bulk and tap density,
`compression characteristics, hygroscopicity, flowability, melting
`point, moisture content, moisture-absorption isotherms, particle
`size distribution, rheology, specific surface area, and solubility.
`Scanning electron microphotographs (SEMs) are also included
`for many of the excipients. The Handbook contains information
`from various international sources, but also includes laboratory
`data determined specifically for the Handbook and personal ob-
`servation and comments from the monograph author, steering
`committee members, and the editor. It also contains information
`on the safe use and potential toxicity of the materials.
`All of the monographs in the Handbook are thoroughly cross-
`referenced and indexed so that excipients may be identified
`by either a chemical, nonproprietary, or trade name. Most
`
`Preface xv
`
`monographs list related substancets) to help the formulator
`develop a list of possible materials for use in a new dosage
`form or product. Related substances are not directly substi-
`tutable for each other but are excipients that have been used
`for similar purposes in various dosage forms.
`
`The Handbook of Pharmaceutical Excipients is a comprehen-
`sive, uniform guide to the uses, properties, and safety of phar-
`maceutical excipients and is an essential referencesource for
`those involved in the development, production, control or reg-
`ulation of pharmaceutical preparations. Since many pharma-
`ceutical excipients are also used in other applications,
`the
`Handbook of Pharmaceutical Excipients will also be of value
`to persons with an interest in the formulation or production
`of confectionery, cosmetic, and food products.
`
`Arrangement
`
`The Handbook consists of monographs that are divided into 22
`sections to make it easy for the reader to go directly to the
`information of interest. Although it was originally intended that
`each monograph contain only information about a single excip-
`ient, it rapidly became clear that some substances or groups of
`substances must be discussed together. This gave rise to such
`monographs as ‘Coloring Agents’ and ‘Hydrocarbons.’ In addi-
`tion, some materials have more than one monograph depending
`on the physical characteristics of the material due mainly to its
`preparation. A good example of this is the various starch mono-
`graphs, particularly Starch vs. Pregelatinized Starch. Regardless
`of the complexity of the monograph they are all divided in 22
`sections as follows:
`
`xooo_\1cxLn.|>uo1\>
`
`1. Nonproprietary Names
`. Synonyms
`.Chemical Name and CAS Registry Number
`. Empirical Formula and Molecular Weight
`. Structural Formula
`
`. Functional Category
`Applications in Pharmaceutical Formulation or Technology
`. Description
`. Pharmacopeial Specifications
`10. Typical Properties
`11. Stability and Storage Conditions
`12. Incompatibilities
`13. Method of Manufacture
`
`14. Safety
`15. Handling Precautions
`16. Regulatory Status
`17. Pharmacopeias
`18. Related Substances
`19. Comments
`
`20. Specific References
`21. General References
`22. Authors
`
`To make it easy for the first time user, descriptions of the
`sections appear below with information from an example
`monograph if needed.
`Section 1, Nonproprietary Names, lists the excipient names
`used in the current British Pharmacopoeia, European Pharma-
`copeia, Japanese Pharmacopeia, and the United States Phar-
`macopeia. For nonpharmacopeial excipients the appropriate
`approved name, e.g., USAN or INN is indicated.
`Section 2, Synonyms, lists other names for the excipient, in-
`cluding trade names used by suppliers; trade names are listed
`in italics. The inclusion of one supp1ier’s trade name and the
`absence of others should in no way be interpreted as an
`
`

`
`
`
`xvi Preface
`
`endorsement of one supplier’s product over the other. The
`large number of suppliers internationally makes it impossible
`to include all the trade names.
`
`Section 3, Chemical Name and CAS Registry Number, indi-
`cates the unique Chemical Abstract Services number for an ex-
`cipient along with the chemical name, e.g., Acacia [9000—0l-5].
`
`Sections 4 and 5, Empirical Formula and Molecular Weight
`and Structural Formula, are self-explanatory. Many excipi-
`ents are not pure chemical substances,
`in which case their
`composition is described either here or in Section 8.
`
`Section 6, Functional Category, lists the function(s) that an
`excipient is generally thought to perform, e.g., diluent, emul-
`sifying agent, etc.
`
`Section 7, Applications in Pharmaceutical Formulation or
`Technology, describes the various applications of the excipient.
`
`Section 8, Description, includes details of the physical ap-
`pearance of the excipient, e.g., white or yellow flakes, etc.
`
`Section 9, Pharmacopeial Specifications, briefly presents the
`compendial standards for the excipient. Information included is
`obtained from the British Pharmacopoeia (BP), European Phar-
`macopeia (PhEur), Japanese Pharmacopeia (JP), and the United
`States Pharmacopeia"/National Formulary (USP). Information
`from the JP and USP are included if the substance is in those
`compendia. Information from the PhEur is also included. If the
`excipient is not in the PhEur but is included in the BP, information
`is included from the BP. The pharmacopeias are continually up-
`dated and revisions or supplements are published. It was neces-
`sary to select a point in time and use that as our reference when
`selecting the information to be included in this section. Therefore
`the information is from the following volumes:
`BP — 1998 Edition
`JP — Thirteenth Edition 1996
`
`PhEur — Third Edition plus supplements to 1999
`USP — USP 24 NF 19 2000 Edition
`
`Since the USP and NF were combined into a single reference
`many years ago it was felt that a single abbreviation would
`be sufficient. Therefore throughout the Handbook whenever
`the USP abbreviation is used it refers to this combined text.
`
`Section 10, Typical Properties, describes the physical prop-
`erties of the excipient which are not shown in Section 9. All
`data are for measurements made at 20°C unless otherwise
`indicated. Where the solubility of the excipient is described
`in words, the following terms describe the solubility ranges:
`
`Very soluble
`Freely soluble
`Soluble
`Sparingly soluble
`Slightly soluble
`Very slightly soluble
`Practically insoluble
`or insoluble
`
`1 part in less than 1
`1 part in 1-10
`1 part in 10-30
`1 part in 30-100
`1 part in 100-1000
`1 part in 1000-10 000
`1 part in more than 10 000
`
`Experimental data were determined specifically for the Hand-
`book and are included in this section. Data from the HPE
`Laboratory Project in support of the third edition are clearly
`marked as such. The methods that were used to collect that
`data are included in Appendix II: HPE Laboratory Meth-
`ods. Data from the HPE Laboratory Project performed for the
`first edition are either replaced by the new data or referenced
`as such in each monograph. The reader is referred to the ear-
`lier editions of this book for the methods used.
`
`Section 11, Stability and Storage Conditions, describes the con-
`ditions under which the bulk material as received from the sup-
`plier should be stored. In addition some monographs report on
`storage and stability of the dosage forms that contain the excip-
`ient.
`
`Section 12, Incompatibilities, describes the reported incompati-
`bilities for the excipient either with other excipients or with active
`ingredients. If an incompatibility is not listed it does not mean it
`does not occur but simply that it has not been reported or is not
`well known. Every formulation should be tested for incompati-
`bilities prior to use in a commercial product.
`
`Section 13, Method of Manufacture, describes the common
`methods of manufacture and additional processes that are used
`to give the excipient its physical characteristics. In some cases
`the possibility of impurities will be indicated in the method
`of manufacture.
`
`Section 14, Safety, describes briefly the types of formulations in
`which the excipient has been used and presents relevant data con-
`cerning possible hazards and adverse reactions that have been re-
`ported. Relevant animal toxicity data are also shown.
`
`Section 15, Handling Precautions, indicates possible hazards
`associated with handling the excipient and makes recommen-
`dations for suitable containment and protective methods. A
`familiarity with current good laboratory practice (GLP) and
`current good manufacturing practice (GMP) and standard
`chemical handling procedures is assumed.
`_
`
`Section 16, Regulatory Status, describes the accepted uses
`in foods and licensed pharmaceuticals where known. The sta-
`tus of excipients varies from one nation to another, even in
`this time of harmonization. Dependence on this reference in
`place of checking with the regulatory body in the nation in
`which the product is to be sold is unwise.
`
`Section 17, Pharmacopeias, lists the pharmacopeias in which
`the excipient is listed. If the excipient is listed in the European
`Pharmacopeia (PhEur), countries that are party to the PhEur
`are not listed; only “Eur” is. The following countries are party
`to the PhEur: Austria, Belgium, Bosnia-Herzegovina, Croatia,
`Cyprus, Czech Republic, Denmark, Finland, France, Germany,
`Greece, Iceland, Ireland, Italy, Luxembourg, the Netherlands,
`Norway, Portugal, Slovakia, Slovenia, Spain, Sweden, Swit-
`zerland, Turkey,
`the United Kingdom of Great Britain and
`Northern Ireland, and the former Yugoslav Republic of Mace-
`donia. The information from the four major pharmacopeias is
`listed in Section 9.
`
`Section 18, Related Substances, lists the excipients similar
`to the excipient discussed in the monograph. The reader
`should look at the monographs for the related substance for
`comparative information.
`
`Section 19, Comments, includes additional information and
`observations relevant to the excipient. Where appropriate, the
`different grades of the excipient available are discussed. Com-
`ments are the opinion of the listed author(s) unless referenced
`or indicated otherwise.
`
`Section 20, Specific References, is a list of references cited
`within the monograph.
`
`Section 21, General References, lists references which have
`general information about this type of excipient or the types
`of dosage forms made with these excipients.
`
`Section 22, Authors, lists in alphabetical order the current authors
`of the monograph. Authors of previous editions can be found in
`the earlier editions.
`
`

`
`Index
`
`Note: In this index, proprietory names are in
`italic type; functional categories are in
`boldface type; See also refers to related
`categories.
`
`A—17, 236
`A-31, 236
`A-70, 236
`Ablunol 80, 511
`Ablunol S—40, 511
`Ablunol S-60, 511
`Ablunol S-85, 511
`Abmcol LG, 225
`Absolute alcohol, 8
`Absorbable dusting powder, 531
`Acacia,
`1
`Acaciae gummi, 1
`Ac-Di—S0l, 160
`Acesulfame K, 3
`Acesulfame potassium, 3, 28
`Acetate, phenylmercuric, 374, 378, 381, 562
`(Acetato—0)phenylmercury, 374
`(Acetato)phenylmercury, 374
`Acetone, dihydroxy, 149
`Acetone chloroform, 126
`Acetoxyphenylmercury, 374
`Acetyl phthalyl cellulose, 99
`Acetylic acid, 535
`Acetyltributyl citrate, 573
`Acetyltriethyl citrate, 574
`Acid(s). See also Ester(s)
`acetylic, 535
`aleurific, 463
`alginic, 10, 445, 446, 465, 466
`allomalenic, 213
`apple, 311
`_
`ascorbic, 21, 26, 469
`2—benzenedicarboxylic, 182
`benzeneformic, 38
`benzeneocarboxylic, 38
`benzoic, 38, 472
`beta-apo—8’ carotenoic, ethyl ester of (C30),
`146
`boletic, 213
`(E)—2—butenedioic, 213
`trans—butenedioic, 213
`carbolic, 367
`carbonic, 56, 440
`carotenoic, beta—apo—8’, ethyl ester of
`(C30), 146
`cevitaminic, 21
`chlorohydric, 238
`citric, 141, 312, 573
`citric monohydrate, 140
`cordycepic, 324
`cresylic, 158
`decanedioic, 178
`(2R, 3R)-2,3—dihydroxybutane—1,4-dioic,
`558
`
`[R—(R+vR+)]-2,3-dihydroxybutanedioic, 558
`[S-(R‘"'R+)]-2,3-dihydroxybutanedioic, 558
`2,3—dihydroxybutanedioic, 558
`2,3-dihydroxysuccinic, 558
`disulfurous, 490
`dracylic, 38
`L—(+)—2,3-dyhydroxybutanedioic, 558
`edetic, 191
`eliac, 356
`1,2-ethenedicarboxylic, 213
`ethylenediaminetetraacetic, 191
`(ethylenedinitro)tetraacetic, 191
`ethylformic, 498, 499
`ethyl pyromeconic, 201
`fumaric, 213, 312, 505
`hexadecanoic, 535
`hexadecylic, 535
`(E,E)-hexa-2,4—dienoic, 508
`2,4—hexadienoic, 508
`hydrochloric, 238
`concentrated, 239
`dilute, 239
`2—hydroxy-1,4—butanedioic, 31 1
`hydroxybutanedioic, 31 1
`(RS)—(i)-hydroxybutanedioic, 31 1
`1—hydroxy—1,2-ethanecarboxylic, 31 1
`7-hydroxypropionic, 272
`(R)—(—)—2—hydroxypropionic, 272
`(S)—(+)—2—hydroxypropionic, 272
`2—hydroxypropionic, 272
`2-hydroxysuccinic, 311
`D1.-lactic, 272
`lactic, 16, 272
`larixinic, 320
`lichenic, 213
`D—malic, 311, 312
`L—malic, 311, 312
`malic, 214, 311
`methylacetic, 498, 499
`2-methyl pyromeconic, 320
`milk, 272
`myristic, isopropyl ester of, 265
`cis—9-octadecanoic, 356
`(Z)—9—octadecanoic, 356
`9,10-octadecanoic, 356
`octadecanoic, 225, 534
`9—octadecanoic (Z), monoester with
`1,2,3-propanetriol, 223
`(Z)—9—octadecenoic, 203
`oleic, 203, 204, 356
`oleinic, 356
`palmitic, 535
`phenic, 367
`phenolic, 367
`phenylcarboxylic, 38
`phenylformic, 38
`phenylic, 367
`phosphoric, 493
`polyacrylic, 79
`polymannuronic, 10
`propanoic, 498, 499
`2-propenylacrylic, 508
`propionic, 499
`sebacic, 178
`shelloic, 463
`silicic, light anhydrous, 143
`
`Index 645
`
`sorbic, 432, 508
`stearic, 72, 305, 422, 534, 608, 609
`'purified, 535, 536
`sulfo-butanedioic, 188
`D-(—)-tartaric, 559
`DL-(i-)-tartaric, 558
`ll-tartaric, 558
`dl-tartaric, 558
`L-tartaric, 558
`l—tartaric, 558
`tartaric, 214, 312, 558
`tetracemic, 191
`tetradecanoic, 1—methylethyl ester of, 265
`trans—butenedioc, 213
`trans—1,2-ethylenedicarboxylic, 213
`trisodium 2—hydroxy—1,2,3—
`propanetricarboxylic, 483
`Acid brilliant green BS (lissamine green), 146
`Acidfuchsine (D&C red #33), 147
`Acid fuchsine (D&C red #33 lake), 148
`Acidifying agents. See also Acidulants
`hydrochloric acid, 238
`lactic acid, 272
`tartaric acid, 558
`Acid sodium phosphate, 496
`Acidulants. See also Acidifying agents
`fumaric acid, 213
`lactic acid, 272
`malic acid, 311
`tartaric acid, 558
`Acidum ascorbicum, 21
`Acidum benoicum, 38
`Acidum hydrochloricum concentratum, 238
`Acidum hydrochloricum dilutum, 239
`Acidum oleum, 356
`Acidum stearicum, 534
`Acidum tartaricum, 558
`Acritamer, 79
`Acrylic acid polymer, 79
`Additives, color. See Coloring agents and
`specific agents
`Adseps lanae, 286
`Adeps lanae cum aqua, 290
`Adeps neutralis, 550
`Adeps solidus, 550
`Admul, 225
`Adsorbents
`bentonite, 30
`cellulose
`
`microcrystalline, 102, 109
`powdered, 107
`colloidal silicon dioxide, 143
`kaolin, 269
`magnesium aluminum silicate, 295
`Advantose 100, 322
`Advawax I40, 225
`Aeropres I7, 236
`Aeropres 31, 236
`Aeropress I08, 236
`Aerosil, 143
`Aerosol propellants, 83
`chlorodifluoroethane (HCFC), 132
`difluoroethane (HFC), 184
`dimethyl ether, 186
`HCFC (chlorodifluoroethane), 132
`heptafluoropropane (HFC), 234
`
`L
`
`

`
`646 Index
`
`HFC (difluoroethane), 184
`hydrocarbons (HC), 236
`nitrogen, 352
`nitrous oxide, 353, 354
`tetrafluoroethane (HFC), 560
`Air displacement agents
`carbon dioxide, 83
`nitrogen, 352
`Airvol, 424
`Akucell, 87
`Alba red (D&C red #39), 147
`Alboline, 345
`Albuconn, 5
`Albumin, 5
`bovine serum, 6
`human solution, 5
`Albuminar, 5
`Albumini humani solutio, 5
`Albuminisol, 5
`Albumin solution, 5
`Albuspan, 5
`Albutein, 5
`Alcohol(s), 7
`absolute, 8
`[3—aminoethyl, 350
`benzyl, 41
`cetearyl, 112
`cetostearyl, 112, 120, 538, 586
`cetyl, 113, 117, 538
`dehydrated, 8
`denatured, 8
`dilute, 8
`furfuryl, 230
`[3-hydroxyethyl phenyl, 370
`isopropyl, 8, 263
`lanolin, 139, 287, 288-290, 346, 348, 349,
`363, 365
`mineral oil, 346, 348, 349
`octadecyl, 537
`paraffin, 365
`petrolatum, 289, 363, 365
`B—phenylethyl, 372
`2-phenylethyl, 372
`phenylethyl, 127, 372
`phenylic, 367
`polyvinyl, 424
`sec—propyl, 263
`propyl, 264
`propylic, 264
`stearyl, 113, 120, 537, 635
`B,B,B-trichloro-tert—butyl, 126
`wool, 288, 365
`Alcohol benzylicus, 41
`Alcohol cetylicus, 117
`Alcohol cetylicus et stearylicus, 112
`Alcohol isopropylicus, 263
`Alcohol stearylicus, 537
`Alcoholis adipis lanae, 288
`Alcoramnosan, 240
`Aldehyde
`ethylprotocatechuic, 208
`methylprotocatechoic, 576
`vanillin, 576
`Aldo MS, 225
`Aldo M0, 223
`Aleuritic acid, 463
`
`Alfadex, 165
`Algin, 465
`.
`Alginate, 6
`Alginic acid, 10, 445, 446, 465, 466
`Aliphatic polyesters, 13, 272, 273
`Alixural purple SS (D&C violet #2 lake), 148
`Alizarin cyanine (D&C green #5), 147
`Alizarin cyanine (D&C green #5 lake), 148
`Alizurol purple SS (D&C violet #2), 147
`Alkalizing agents
`diethanolamine (DEA), 180
`monoethanolamine, 350
`potassium citrate, 429
`sodium bicarbonate, 474
`sodium citrate, 482
`triethanolamine, 572
`Alkamuls SMS, 511
`Alkamuls STS, 511
`Alkylbenzyldimethylammonium chloride, 33
`Alkyl benzyl dimethyl ammonium chloride, 33
`Alkyldimethyl(phenylmethyl)ammonium
`chloride, 33
`Allomalenic acid, 213
`Allura red AC (D&C red #40), 147
`Alpha-carotene, 146
`Alpha-cyclodextrin, 165
`Alpha-cyclosamylose, 165
`Alpha-dextrin, 165
`Alpha tocopherol, 18
`d-Alpha tocopherol, 19
`d—Alpha tocopheryl acetate, 19
`dl—Alpha tocopheryl acetate, 19
`d~A1pha tocopheryl acid succinate, 19
`dl—Alpha tocopheryl acid succinate, 19
`Alphazurine FG (D&C blue #4), 147
`Alphazurine FG (D&C blue #4 lake), 148
`Alumina, 149
`Aluminum magnesium silicate, 295
`Aluminum powder, 149
`Aluminum silicate, hydrated, 269
`Alvanol, 424
`Amalty, 313
`Amberlite IRP-88, 383
`Amberlite resins, physico-chemical properties
`summary, 384
`Amerchol CAB, 365
`Americhal L-101, 349
`Amido, 522
`Amidon, 522
`Amilo, 522
`2—Aminoethanol, 350
`[3—Arninoethyl alcohol, 350
`3-Amino-N-(oc-carboxyphenethyl)succinamic
`acid N-methyl ester, 27
`3-Amino—N-(cc-methoxycarbonylphenethy1)—
`succinnamic acid, 27
`Ammonio methacrylate copolymer, 401
`Ammonium, saccharin, 455 ‘
`Ammonium citrate, ferric, 149
`Ammonium ferrocyanide, ferric, 149
`Amorphous wax, 591
`Amylopectin, 527
`0t—Amy1ose, 527
`Amylum, 522
`Anatase titanium dioxide, 565
`
`r
`1
`Anhydride, titanic, 565
`
`1,4—Anhydro—D—glucitol, 511
`Anhydrosorbital monoisostearate, 511
`Anhydrosorbitol monostearate, 511
`Anhydrous citric acid, 141
`Anhydrous dextrose, 177
`Anhydrous dibasic calcium phosphate, 60
`Anhydrous dibasic sodium phosphate, 493
`Anhydrous Emcompress, 60
`Anhydrous 4-0—oc-D-glucopyranosyl-[3-D-
`glucopyranose, 322
`Anhydrous lanolin, 286
`Anhydrous magnesium carbonate, 301
`Anhydrous monobasic sodium phosphate,
`496
`
`Anhydrous potassium citrate, 430
`Anhydrous silicic acid, light, 143
`Anhydrous sodium citrate, 483
`Anhydrous sodium propionate, 499
`Anhydrous sodium salt, 499
`Anhydrous sodium sulfite, 491
`Anion—exchange Amberlite resins, 384
`Anionic emulsifying wax, 585
`Annatto extract, 149
`Anthocyanins, 146
`Anthracine 12, 49
`Anticaking agents
`calcium phosphate, tribasic, 68
`magnesium trisilicate, 309
`talc, 555
`Anticoagulants
`editic acid (EDTA), 191
`Antimicrobial preservatives. See also
`Antiseptics; Disinfectants
`
`acids
`benzoic, 38
`editic (EDTA), 191
`phenolic, 367
`sorbic, 508
`alcohols, 7
`benzyl, 41
`isopropyl, 263
`benzethonium chloride, 33
`bronopol, 46
`butylparaben, 53
`,
`cetrimide, 114
`chlorhexidine, 121
`chlorobutanol, 126
`chlorocresol, 129
`cresol, 158
`ethylparaben, 205
`glycerol, 220
`imidurea, 261
`methylparaben, 340
`phenol, 367
`phenoxyethanol, 370
`phenylethyls, alcohol, 372
`phenylmercuric acetate, 374, 378, 381
`phenylmercuric borate, 377, 381
`phenylmercuric nitrate, 379
`potassium sorbate, 431
`propylene glycol, 442
`propylparaben, 450
`sodium benzoate, 471
`sodium propionate, 498
`sorbic acid, 508
`thimerosol, 562
`
`

`
`
`
`Avicel, 102
`Aytex R 522
`Azote, 352
`
`B-1459, 599
`
`Bacteriostatic water, for injection, 583
`Bases
`
`for medicated confectionery
`polydextrose, 389
`sucrose, 539
`ointment
`alcohols, 288, 365
`lanolin, 286, 290
`paraffin, 358
`petrolatum, 362
`polyethylene glycol, 392
`organic, meglumine, 332
`suppository, 398, 579
`hard fat, 550
`polyethylene glycol, 392
`Basic phenylmercury nitrate, 379
`Beeswax, white, 595
`Beetroot red (betanin), 146
`Beet sugar, 539
`1,2—Benisothiazolin-3—one 1,1-dioxide, 454
`Benne oil, 460
`Bentonite, 30, 269
`Bentonite magma, 32
`Bentonitum, 30
`Benzalkonii chloridum, 33
`Benzalkonium chloride, 33
`Benzene, [3-hydroxyethyl, 372
`l,2—Benzenedicarboxylic acid, 182
`1,2-Benzenedicarboxylic acid dibutyl ester,
`183
`Benzeneethanol, 372
`Benzeneformic acid, 38
`Benzenemethanol, 41
`Benzenocarboxylic acid, 38
`Benzenylcarboxylate, 44
`Benzethonium chloride, 35
`1,2—Benzisothiazol—3(2H)—one 1,1 dioxide, 454
`Benzoic acid, 38, 472
`Benzoic acid benzyl ester, 44
`Benzoic acid phenylmethyl ester, 44
`Benzoic sulfimide, 454
`Benzosulfimide, 454
`1,2-Benzothiazolin-3—one 1,1-dioxide sodium
`salt, 457
`Benzyl alcohol, 41
`Benzyl benzoate, 44
`Benzyl carbinol, 372
`Benzylis benzoas, 44
`Benzylmethanol, 372
`Benzyl phenylformate, 44
`Beta—apo—8'-carotenal, 146
`Beta—apo—8’—carotenoic acid, ethyl ester of
`(C30), 146
`Beta-carotene, 146, 149, 150
`Beta-cycloamylose, 165
`Beta cyclodextrin, 165
`Betacyclodextrinun, 165
`Betadex, 165
`Beta-dextrin, 165
`Betanin (beetroot red), 146
`Beta tocopherol, 20
`
`Index 647
`
`Betonite, 298
`BFI (Brittle Fracture Index), 637
`BHA, '49
`Bicarbonate
`potassium, 476
`sodium, 474
`Binders
`1
`acacia,
`alginic acid, 10
`carboxymethylcellulose, 87
`cellulose
`hydroxyethyl, 240
`hydroxypropyl, 244, 249
`dcxtrin, 172
`flavoring fixative, ethylcellulose, 195
`gelatin, 215
`glucose, liquid, 218
`guar gum, 232
`hydrogenated Vegetable oil, type I, 578
`hydroxyethyl cellulose, 240
`hydroxypropyl methylcellulose, 252
`liquid glucose, 218
`magnesium aluminum silicate, 295
`maltodextrin, 317
`methylcellulose, 252, 336
`polyethylene oxide, 399
`polymethacrylates, 401
`povidone, 433
`sodium alginate, 465
`starch, 522, 528
`vegetable oil, hydrogenated, type I, 578
`zein, 606
`Biopure 100, 261
`Biphosphate, sodium, 496
`N,N’5Bis(4—chlorophenyl)—3,1,2-diimino—
`2,4,1 1, 13—tetraaztetradecane-
`diimidamine, 121
`1,4-Bis(2-ethylhexyl) ester, 188
`Bis(2-ethylhexyl) sodium sulfosuccinate, 188
`1,2—Bis(2—ethylhexyl) sulfosuccinate, 189
`Bis(hydroxyethyl)amine, 180
`Bismuth oxychloride, 149
`l,6—Bis [N’-(p—chlorophenyl)]—N5' biguanido
`hexane, 121
`Bisomel, 265
`Bis-sorb, 531
`Bisulfite, 491
`BKC, 33
`Black PN, 150
`Blanose, 87
`Bleached shellac, 462
`Bleached wax, 595
`Blue coloring agents, 147
`BNPDBron0sol, 46
`Boletic acid, 213
`Bolus alba, 269
`Bonding Index (B1), 637
`Borate
`
`phenylmercuric, 375, 377, 562
`phenylmercury, 377
`Borculo whey products, lactoses, 279, 282
`Bourbonal, 208
`Bovine serum albumin, 6
`Brazil wax, 587
`Breox PEG, 392
`Brij, 407
`
`Antioxidant synergists
`editic acid (EDTA), 191
`Antioxidants
`acids
`ascorbic, 21
`fumaric, 213
`malic, 311
`alpha tocopherol, 18
`ascorbic acid palmitate, 25
`butylated hydroxyanisole, 49
`propyl gallate, 447
`sodium ascorbate, 468
`sodium metabisulfite, 490
`Antiseptics, 46. See also Antimicrobial
`preservatives; Disinfectants
`benzalkonium chloride, 33
`cetrimide, 114
`chlorhexidine, 121
`phenylmercuric acetate, 374, 378
`phenylmercuric borate, 377
`phenylmercuric nitrate, 379
`thimerosol, 562
`APM, 27
`Apple acid, 311
`Aquacoat, 195
`Aqua purificata, 580
`Aquasorb, 87
`Aquuteric, 99
`Aracel 161, 225
`Aracel 169, 225
`Arachis oil, 360
`Arachis oleum, 360
`Arcton, 134
`Argilla, 269
`Arlacel C, 511
`Arlacel 20, 511
`Arlacel 40, 511
`Arlacel 60, 511
`Arlacel 80, 511
`Arlacel 83, 511
`Arlacel 85, 511
`Arlacel I80, 223
`Arlacel 987, 511
`Arlatone, 412
`Armostat 801, 225
`Armotan M5, 511
`Armotan ML, 511
`Armotan M0, 511
`Armatan MP, 511
`Ascorbic acid, 21, 26
`Ascorbic acid 6-hexadecanoate, 25
`L—Ascorbic acid monosodium salt, 468
`Ascorbilis palmitas, 25
`Ascorbyl palmitate, 23, 25, 4-69
`Aspartame, 4, 27
`N—ot-L-Aspartyl-L—phenylalanine 1-methyl
`ester, 27
`Aspartyl phenylamine methyl ester, 27
`Assugrin, 485
`A-