Your SlideShare is downloading. ×
Handbook+of+pharmaceutical+excipients,+6th+edition
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Handbook+of+pharmaceutical+excipients,+6th+edition

75,786
views

Published on

excipientes farmaceuticos

excipientes farmaceuticos

Published in: Business, Health & Medicine

3 Comments
25 Likes
Statistics
Notes
No Downloads
Views
Total Views
75,786
On Slideshare
0
From Embeds
0
Number of Embeds
3
Actions
Shares
0
Downloads
3,442
Comments
3
Likes
25
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Handbook of Pharmaceutical Excipients
  • 2. Handbook ofPharmaceutical ExcipientsSIXTH EDITIONEdited byRaymond C Rowe BPharm, PhD, DSC, FRPharmS, FRSC, CPhys, MInstPChief ScientistIntelligensys Ltd, Stokesley, North Yorkshire, UKPaul J Sheskey BSc, RPhApplication Development LeaderThe Dow Chemical Company, Midland, MI, USAMarian E Quinn BSc, MScDevelopment EditorRoyal Pharmaceutical Society of Great Britain, London, UK London . Chicago
  • 3. Published by the Pharmaceutical PressAn imprint of RPS Publishing1 Lambeth High Street, London SE1 7JN, UK100 South Atkinson Road, Suite 200, Grayslake, IL 60030-7820, USAand the American Pharmacists Association2215 Constitution Avenue, NW, Washington, DC 20037-2985, USA# Pharmaceutical Press and American Pharmacists Association 2009 is a trade mark of RPS PublishingRPS Publishing is the publishing organisation of the Royal Pharmaceutical Society of Great BritainFirst published 1986Second edition published 1994Third edition published 2000Fourth edition published 2003Fifth edition published 2006Sixth edition published 2009Typeset by Data Standards Ltd, Frome, SomersetPrinted in Italy by L.E.G.O. S.p.A.ISBN 978 0 85369 792 3 (UK)ISBN 978 1 58212 135 2 (USA)All rights reserved. No part of this publication may bereproduced, stored in a retrieval system, or transmitted in anyform or by any means, without the prior written permissionof the copyright holder. The publisher makes no representation, express or implied,with regard to the accuracy of the information contained inthis book and cannot accept any legal responsibility orliability for any errors or omissions that may be made.A catalogue record for this book is available from the British Library
  • 4. ContentsPreface x Benzalkonium Chloride 56Arrangement xi Benzethonium Chloride 59Acknowledgments xiii Benzoic Acid 61Notice to Readers xiiiInternational Steering Committee xiv Benzyl Alcohol 64Editorial Staff xv Benzyl Benzoate 66Contributors xvi Boric Acid 68About the Editors xx Bronopol 70New Monographs xxi Butylated Hydroxyanisole 73Related Substances xxiiBibliography xxiv Butylated Hydroxytoluene 75Abbreviations xxv Butylene Glycol 77Units of Measurement xxvii Butylparaben 78MonographsA CAcacia 1 Calcium Acetate 82Acesulfame Potassium 3 Calcium Alginate 83Acetic Acid, Glacial 5 Calcium Carbonate 86Acetone 7 Calcium Chloride 89Acetyltributyl Citrate 8 Calcium Hydroxide 91Acetyltriethyl Citrate 10 Calcium Lactate 92Adipic Acid 11 Calcium Phosphate, Dibasic Anhydrous 94Agar 13 Calcium Phosphate, Dibasic Dihydrate 96Albumin 14 Calcium Phosphate, Tribasic 99Alcohol 17 Calcium Silicate 101Alginic Acid 20 Calcium Stearate 103Aliphatic Polyesters 23 Calcium Sulfate 105Alitame 28 Canola Oil 108Almond Oil 29 Carbomer 110Alpha Tocopherol 31 Carbon Dioxide 115Aluminum Hydroxide Adjuvant 34 Carboxymethylcellulose Calcium 117Aluminum Monostearate 35 Carboxymethylcellulose Sodium 118Aluminum Oxide 37 Carrageenan 122Aluminum Phosphate Adjuvant 38 Castor Oil 126Ammonia Solution 39 Castor Oil, Hydrogenated 128Ammonium Alginate 41 Cellulose, Microcrystalline 129Ammonium Chloride 42 Cellulose, Microcrystalline andAscorbic Acid 43 Carboxymethylcellulose Sodium 134Ascorbyl Palmitate 46 Cellulose, Powdered 136Aspartame 48 Cellulose, Silicified Microcrystalline 139Attapulgite 51 Cellulose Acetate 141 Cellulose Acetate Phthalate 143B Ceratonia 146Bentonite 53 Ceresin 148
  • 5. vi ContentsCetostearyl Alcohol 150 Erythritol 251Cetrimide 152 Ethyl Acetate 253Cetyl Alcohol 155 Ethyl Lactate 256Cetylpyridinium Chloride 157 Ethyl Maltol 257Chitosan 159 Ethyl Oleate 259Chlorhexidine 162 Ethyl Vanillin 261Chlorobutanol 166 Ethylcellulose 262Chlorocresol 168 Ethylene Glycol Stearates 267Chlorodifluoroethane (HCFC) 171 Ethylene Vinyl Acetate 268Chlorofluorocarbons (CFC) 173 Ethylparaben 270Chloroxylenol 176Cholesterol 178 FCitric Acid Monohydrate 181 Fructose 273Coconut Oil 184 Fumaric Acid 276Colloidal Silicon Dioxide 185Coloring Agents 189 G Gelatin 278Copovidone 196Corn Oil 199 Glucose, Liquid 282 Glycerin 283Corn Starch and Pregelatinized Starch 200 Glyceryl Behenate 286Cottonseed Oil 202Cresol 203 Glyceryl Monooleate 288 Glyceryl Monostearate 290Croscarmellose Sodium 206Crospovidone 208 Glyceryl Palmitostearate 293 Glycine 295Cyclodextrins 210 Glycofurol 297Cyclomethicone 215 Guar Gum 298DDenatonium Benzoate 217 HDextrates 218 Hectorite 301Dextrin 220 Heptafluoropropane (HFC) 303Dextrose 222 Hexetidine 304Dibutyl Phthalate 225 Hydrocarbons (HC) 306Dibutyl Sebacate 227 Hydrochloric Acid 308Diethanolamine 228 Hydrophobic Colloidal Silica 309Diethyl Phthalate 230 Hydroxyethyl Cellulose 311Difluoroethane (HFC) 232 Hydroxyethylmethyl Cellulose 314Dimethicone 233 Hydroxypropyl Betadex 315Dimethyl Ether 235 Hydroxypropyl Cellulose 317Dimethyl Phthalate 236 Hydroxypropyl Cellulose, Low-substituted 322Dimethyl Sulfoxide 238 Hydroxypropyl Starch 325Dimethylacetamide 241 Hypromellose 326Disodium Edetate 242 Hypromellose Acetate Succinate 330Docusate Sodium 244 Hypromellose Phthalate 333E IEdetic Acid 247 Imidurea 337Erythorbic Acid 250 Inulin 339
  • 6. Contents viiIron Oxides 340 Methionine 436Isomalt 342 Methylcellulose 438Isopropyl Alcohol 346 Methylparaben 441Isopropyl Myristate 348 Mineral Oil 445Isopropyl Palmitate 350 Mineral Oil, Light 447 Mineral Oil and Lanolin Alcohols 449K Monoethanolamine 450Kaolin 352 Monosodium Glutamate 452 Monothioglycerol 454L Myristic Acid 455Lactic Acid 355 Myristyl Alcohol 456Lactitol 357Lactose, Anhydrous 359 NLactose, Inhalation 362 Neohesperidin Dihydrochalcone 458Lactose, Monohydrate 364 Neotame 460Lactose, Monohydrate and Corn Starch 370 Nitrogen 461Lactose, Monohydrate and Microcrystalline Cellulose 371 Nitrous Oxide 463Lactose, Monohydrate and Povidone 373Lactose, Monohydrate and Powdered Cellulose 374 OLactose, Spray-Dried 376 Octyldodecanol 465Lanolin 378 Oleic Acid 466Lanolin, Hydrous 380 Oleyl Alcohol 468Lanolin Alcohols 382 Olive Oil 470Lauric Acid 383Lecithin 385 PLeucine 387 Palmitic Acid 473Linoleic Acid 389 Paraffin 474 Peanut Oil 476M Pectin 478Macrogol 15 Hydroxystearate 391 Pentetic Acid 480Magnesium Aluminum Silicate 393 Petrolatum 481Magnesium Carbonate 397 Petrolatum and Lanolin Alcohols 484Magnesium Oxide 400 Phenol 485Magnesium Silicate 402 Phenoxyethanol 488Magnesium Stearate 404 Phenylethyl Alcohol 490Magnesium Trisilicate 408 Phenylmercuric Acetate 492Maleic Acid 410 Phenylmercuric Borate 494Malic Acid 411 Phenylmercuric Nitrate 496Maltitol 414 Phospholipids 499Maltitol Solution 416 Phosphoric Acid 503Maltodextrin 418 Polacrilin Potassium 504Maltol 421 Poloxamer 506Maltose 422 Polycarbophil 509Mannitol 424 Polydextrose 513Medium-chain Triglycerides 429 Poly (DL-Lactic Acid) 515Meglumine 431 Polyethylene Glycol 517Menthol 433 Polyethylene Oxide 522
  • 7. viii ContentsPolymethacrylates 525 Sodium Citrate Dihydrate 640Poly(methyl vinyl ether/maleic anhydride) 534 Sodium Cyclamate 643Polyoxyethylene Alkyl Ethers 536 Sodium Formaldehyde Sulfoxylate 645Polyoxyethylene Castor Oil Derivatives 542 Sodium Hyaluronate 646Polyoxyethylene Sorbitan Fatty Acid Esters 549 Sodium Hydroxide 648Polyoxyethylene Stearates 554 Sodium Lactate 650Polyoxylglycerides 557 Sodium Lauryl Sulfate 651Polyvinyl Acetate Phthalate 562 Sodium Metabisulfite 654Polyvinyl Alcohol 564 Sodium Phosphate, Dibasic 656Potassium Alginate 566 Sodium Phosphate, Monobasic 659Potassium Alum 567 Sodium Propionate 661Potassium Benzoate 569 Sodium Starch Glycolate 663Potassium Bicarbonate 570 Sodium Stearyl Fumarate 667Potassium Chloride 572 Sodium Sulfite 669Potassium Citrate 574 Sodium Thiosulfate 671Potassium Hydroxide 576 Sorbic Acid 672Potassium Metabisulfite 577 Sorbitan Esters (Sorbitan Fatty Acid Esters) 675Potassium Sorbate 579 Sorbitol 679Povidone 581 Soybean Oil 682Propionic Acid 586 Starch 685Propyl Gallate 587 Starch, Pregelatinized 691Propylene Carbonate 590 Starch, Sterilizable Maize 695Propylene Glycol 592 Stearic Acid 697Propylene Glycol Alginate 594 Stearyl Alcohol 700Propylparaben 596 Sucralose 701Propylparaben Sodium 599 Sucrose 703Pyrrolidone 600 Sucrose Octaacetate 707 Sugar, Compressible 709R Sugar, Confectioner’s 710Raffinose 603 Sugar Spheres 712 Sulfobutylether b-Cyclodextrin 714S Sulfur Dioxide 718Saccharin 605 Sulfuric Acid 719Saccharin Sodium 608 Sunflower Oil 721Safflower Oil 610 Suppository Bases, Hard Fat 722Saponite 612Sesame Oil 614Shellac 616 TSimethicone 619 Tagatose 727Sodium Acetate 620 Talc 728Sodium Alginate 622 Tartaric Acid 731Sodium Ascorbate 625 Tetrafluoroethane (HFC) 733Sodium Benzoate 627 Thaumatin 735Sodium Bicarbonate 629 Thimerosal 736Sodium Borate 633 Thymol 739Sodium Carbonate 635 Titanium Dioxide 741Sodium Chloride 637 Tragacanth 744
  • 8. Contents ixTrehalose 746 Wax, White 779Triacetin 748 Wax, Yellow 780Tributyl Citrate 749Tricaprylin 751Triethanolamine 754Triethyl Citrate 756 XTriolein 757 Xanthan Gum 782 Xylitol 786VVanillin 760Vegetable Oil, Hydrogenated 762 ZVitamin E Polyethylene Glycol Succinate 764 Zein 790 Zinc Acetate 791W Zinc Stearate 793Water 766Wax, Anionic Emulsifying 770 Appendix I: Suppliers Directory 795Wax, Carnauba 772 Appendix II: List of Excipient ‘E’ Numbers 847Wax, Cetyl Esters 774 Appendix III: List of Excipient ‘EINECS’ Numbers 849Wax, Microcrystalline 775 Appendix IV: List of Excipient Molecular Weights 852Wax, Nonionic Emulsifying 777 Index 855
  • 9. PrefacePharmaceutical dosage forms contain both pharmacologically batch of a specific excipient have been retained as this wasactive compounds and excipients added to aid the formulation considered relevant to the behavior of a material in practice. Overand manufacture of the subsequent dosage form for administration the past few years, there has been an increased emphasis on theto patients. Indeed, the properties of the final dosage form (i.e. its harmonization of excipients. For information on the current statusbioavailability and stability) are, for the most part, highly for each excipient selected for harmonization, the reader is directeddependent on the excipients chosen, their concentration and to the General Information Chapter <1196> in the USP32–NF27,interaction with both the active compound and each other. No the General Chapter 5.8 in PhEur 6.0, along with the ‘State oflonger can excipients be regarded simply as inert or inactive Work’ document on the PhEur EDQM website (http://www.edq-ingredients, and a detailed knowledge not only of the physical and m.eu), and also the General Information Chapter 8 in the JP XV.chemical properties but also of the safety, handling and regulatory The Suppliers Directory (Appendix I) has also been completelystatus of these materials is essential for formulators throughout the updated with many more international suppliers included.world. In addition, the growth of novel forms of delivery has In a systematic and uniform manner, the Handbook ofresulted in an increase in the number of the excipients being used Pharmaceutical Excipients collects essential data on the physicaland suppliers of excipients have developed novel coprocessed properties of excipients such as: boiling point, bulk and tap density,excipient mixtures and new physical forms to improve their compression characteristics, hygroscopicity, flowability, meltingproperties. The Handbook of Pharmaceutical Excipients has been point, moisture content, moisture-absorption isotherms, particleconceived as a systematic, comprehensive resource of information size distribution, rheology, specific surface area, and solubility.on all of these topics. Scanning electron microphotographs (SEMs) are also included for The first edition of the Handbook was published in 1986 and many of the excipients. This edition contains over 130 near-infraredcontained 145 monographs. This was followed by the second (NIR) spectra specifically generated for the Handbook. Theedition in 1994 containing 203 monographs, the third edition in Handbook contains information from various international sources2000 containing 210 monographs and the fourth edition in 2003 and personal observation and comments from monograph authors,containing 249 monographs. Since 2000, the data has also been steering committee members, and the editors.available on CD-ROM, updated annually, and from 2004 online. All of the monographs in the Handbook are thoroughly cross-The fifth edition with its companion CD-ROM, Pharmaceutical referenced and indexed so that excipients may be identified by eitherExcipients 5, contained 300 monographs and was published in a chemical, a nonproprietary, or a trade name. Most monographs2006. This new edition contains 340 excipient monographs with a list related substances to help the formulator to develop a list ofnew text design and enhanced online features, compiled by over 140 possible materials for use in a new dosage form or product. Relatedexperts in pharmaceutical formulation or excipient manufacture substances are not directly substitutable for each other but, infrom Australia, Europe, India, Japan, and the USA. All the general, they are excipients that have been used for similar purposesmonographs have been reviewed and revised in the light of current in various dosage forms.knowledge. There has been a greater emphasis on including The Handbook of Pharmaceutical Excipients is a comprehensive,published data from primary sources although some data from uniform guide to the uses, properties, and safety of pharmaceuticallaboratory projects included in previous editions have been retained excipients, and is an essential reference source for those involved inwhere relevant. Variations in test methodology can have significant the development, production, control, or regulation of pharmaceu-effects on the data generated (especially in the case of the tical preparations. Since many pharmaceutical excipients are alsocompactability of an excipient), and thus cause confusion. As a used in other applications, the Handbook of Pharmaceuticalconsequence, the editors have been more selective in including data Excipients will also be of value to persons with an interest in therelating to the physical properties of an excipient. However, formulation or production of confectionery, cosmetics, and foodcomparative data that show differences between either source or products.x
  • 10. ArrangementThe information consists of monographs that are divided into 22 Section 6, Functional Category, Lists the function(s) that an excipi-sections to enable the reader to find the information of interest ent is generally thought to perform, e.g., diluent, emulsifyingeasily. Although it was originally intended that each monograph agent, etc.contain only information about a single excipient, it rapidly becameclear that some substances or groups of substances should be Section 7, Applications in Pharmaceutical Formulation or Technol-discussed together. This gave rise to such monographs as ‘Coloring ogy, Describes the various applications of the excipient.Agents’ and ‘Hydrocarbons’. In addition, some materials have morethan one monograph depending on the physical characteristics ofthe material, e.g. Starch versus Pregelatinized Starch. Regardless of Section 8, Description, Includes details of the physical appearancethe complexity of the monograph they are all divided into 22 of the excipient, e.g., white or yellow flakes, etc.sections as follows: Section 9, Pharmacopeial Specifications, Briefly presents the com-1 Nonproprietary Names pendial standards for the excipient. Information included is2 Synonyms obtained from the British Pharmacopoeia (BP), European Pharma-3 Chemical Name and CAS Registry Number copeia (PhEur), Japanese Pharmacopeia (JP), and the United4 Empirical Formula and Molecular Weight States Pharmacopeia/National Formulary (USP/USP–NF). Infor-5 Structural Formula mation from the JP, USP and USP–NF are included if the sub-6 Functional Category stance is in those compendia. Information from the PhEur is also7 Applications in Pharmaceutical Formulation or Technology included. If the excipient is not in the PhEur but is included in the8 Description BP, information is included from the BP. Pharmacopeias are conti-9 Pharmacopeial Specifications nually updated with most now being produced as annual editions.10 Typical Properties However, although efforts were made to include up-to-date infor-11 Stability and Storage Conditions mation at the time of publication of this edition, the reader is12 Incompatibilities advised to consult the most current pharmacopeias or supple-13 Method of Manufacture ments.14 Safety15 Handling Precautions Section 10, Typical Properties, Describes the physical properties of16 Regulatory Status the excipient which are not shown in Section 9. All data are for17 Related Substances measurements made at 208C unless otherwise indicated. Where18 Comments the solubility of the excipient is described in words, the following19 Specific References terms describe the solubility ranges:20 General References21 Authors Very soluble 1 part in less than 122 Date of Revision Freely soluble 1 part in 1–10 Descriptions of the sections appear below with information from Soluble 1 part in 10–30an example monograph if needed. Sparingly soluble 1 part in 30–100 Slightly soluble 1 part in 100–1000 Very slightly soluble 1 part in 1000–10 000Section 1, Nonproprietary Names, Lists the excipient names used Practically insoluble or insoluble 1 part in more than 10 000in the current British Pharmacopoeia, European Pharmacopeia,Japanese Pharmacopeia, and the United States Pharmacopeia/ For this edition, near-infrared (NIR) reflectance spectra of samplesNational Formulary. as received (i.e. the samples were not dried or reduced in particle size) were measured using a FOSS NIRSystems 6500 spectro- photometer (FOSS NIRSystems Inc., Laurel, MD, USA) fitted with aSection 2, Synonyms, Lists other names for the excipient, includ- Rapid Content Analyser against a ceramic standard supplied withing trade names used by suppliers (shown in italics). The inclusion the instrument. The instrument was controlled by Vision (versionof one supplier’s trade name and the absence of others should in 2.22) software. Spectra were recorded over the wavelength rangeno way be interpreted as an endorsement of one supplier’s pro- 1100–2498 nm (700 data points) and each saved spectrum was theduct over the other. The large number of suppliers internationally average of 32 scans. Solid powdered samples were measured in glassmakes it impossible to include all the trade names. vials of approximately 20 mm diameter. Each sample was measured in triplicate and the mean spectrum taken. When more than one batch of a material was available, the mean of all the batches isSection 3, Chemical Name and CAS Registry Number, Indicates presented. Liquid samples were measured by transflectance using athe unique Chemical Abstract Services number for an excipient gold reflector (2 Â 0.5 mm optical path-length, FOSS) placed in aalong with the chemical name, e.g., Acacia [9000-01-5]. 45 mm silica reflectance cell against air as the reference. Spectra are presented as plots of (a) log(1/R) vs wavelength (dashed line, scale on right-hand side) and (b) second-derivative log(1/R) vs wave-Sections 4 and 5, Empirical Formula and Molecular Weight and length (solid line, scale on left-hand side). R is the reflectance andStructural Formula, Are self-explanatory. Many excipients are not log(1/R) represents the apparent absorbance. Second-derivativepure chemical substances, in which case their composition is spectra were calculated from the log(1/R) values using an 11 pointdescribed either here or in Section 8. Savitzky-Golay filter with second-order polynomial smoothing. xi
  • 11. xii ArrangementNote, peak positions and amplitudes in the second-derivative Section 15, Handling Precautions, Indicates possible hazards asso-spectrum are very sensitive to the method used to calculate the ciated with handling the excipient and makes recommendationssecond-derivative. for suitable containment and protection methods. A familiarity Where practical, data typical of the excipient or comparative data with current good laboratory practice (GLP) and current goodrepresentative of different grades or sources of a material are manufacturing practice (GMP) and standard chemical handlingincluded, the data being obtained from either the primary or the procedures is assumed.manufacturers’ literature. In previous editions of the Handbook alaboratory project was undertaken to determine data for a variety of Section 16, Regulatory Status, Describes the accepted uses inexcipients and in some instances this data has been retained. For a foods and licensed pharmaceuticals where known. However, thedescription of the specific methods used to generate the data readers status of excipients varies from one nation to another, and appro-should consult the appropriate previous edition(s) of the Hand- priate regulatory bodies should be consulted for guidance.book. Section 17, Related Substances, Lists excipients similar to theSection 11, Stability and Storage Conditions, Describes the condi- excipient discussed in the monograph.tions under which the bulk material as received from the suppliershould be stored. In addition some monographs report on storage Section 18, Comments, Includes additional information and obser-and stability of the dosage forms that contain the excipient. vations relevant to the excipient. Where appropriate, the different grades of the excipient available are discussed. Comments are theSection 12, Incompatibilities, Describes the reported incompatibil- opinion of the listed author(s) unless referenced or indicatedities for the excipient either with other excipients or with active otherwise.ingredients. If an incompatibility is not listed it does not mean itdoes not occur but simply that it has not been reported or is not Section 19, Specific References, Is a list of references cited withinwell known. Every formulation should be tested for incompatibil- the monograph.ities prior to use in a commercial product. Section 20, General References, Lists references which have gen-Section 13, Method of Manufacture, Describes the common meth- eral information about this type of excipient or the types ofods of manufacture and additional processes that are used to give dosage forms made with these excipients.the excipient its physical characteristics. In some cases the possibi-lity of impurities will be indicated in the method of manufacture. Section 21, Authors, Lists the current authors of the monograph in alphabetical order. Authors of previous versions of the mono-Section 14, Safety, Describes briefly the types of formulations in graph are shown in previous printed editions of the text.which the excipient has been used and presents relevant data con-cerning possible hazards and adverse reactions that have been Section 22, Date of Revision, Indicates the date on which changesreported. Relevant animal toxicity data are also shown. were last made to the text of the monograph.
  • 12. AcknowledgmentsA publication containing so much detail could not be produced excipient manufacturers and suppliers who provided helpfulwithout the help of a large number of pharmaceutical scientists information on their products.based world-wide. The voluntary support of over 140 authors has Thanks are also gratefully extended to the staff of thebeen acknowledged as in previous editions, but the current editors Pharmaceutical Press and American Pharmacists Association whowould like to thank them all personally for their contribution. were involved in the production of the Handbook: Tamsin Cousins,Grateful thanks also go to the members of the International Steering Simon Dunton, Rebecca Garner, Julian Graubart, Karl Parsons,Committee who advised the editors and publishers on all aspects of Linda Paulus, Jo Watts, Paul Weller, and John Wilson. The diligentthe Handbook project.Many authors and Steering Committee copy-editing and proofreading by Len Cegielka and Janet Pascoe,members have been involved in previous editions of the Handbook. respectively, helped the authors and editors, we hope, to expressFor others, this was their first edition although not, we hope, their their thoughts clearly, concisely, and accurately.last. We extend our thanks to all for their support. Thanks are alsoextended to Roger Jee, Kelly Palmer, and Tony Moffat at The School Raymond C Rowe, Paul J Sheskey, Marian E Quinnof Pharmacy, University of London for supplying the NIR spectra,to Pfizer PGRD, Sandwich, UK for supplying SEMs, and to July 2009Notice to ReadersThe Handbook of Pharmaceutical Excipients is a reference work is not intended as an endorsement of that supplier or its productscontaining a compilation of information on the uses and properties and, similarly, the unintentional omission of a supplier or productof pharmaceutical excipients, and the reader is assumed to possess from the directory is not intended to reflect adversely on thatthe necessary knowledge to interpret the information that the supplier or its product.Handbook contains. The Handbook of Pharmaceutical Excipients Although diligent effort was made to use the most recenthas no official status and there is no intent, implied or otherwise, compendial information, compendia are frequently revised andthat any of the information presented should constitute standards the reader is urged to consult current compendia, or supplements,for the substances. The inclusion of an excipient, or a description of for up-to-date information, particularly as efforts are currently inits use in a particular application, is not intended as an endorsement progress to harmonize standards for excipients.of that excipient or application. Similarly, reports of incompat- Data presented for a particular excipient may not be representa-ibilities or adverse reactions to an excipient, in a particular tive of other batches or samples.application, may not necessarily prevent its use in other applica- Relevant data and constructive criticism are welcome and may betions. Formulators should perform suitable experimental studies to used to assist in the preparation of any future editions or electronicsatisfy themselves and regulatory bodies that a formulation is versions of the Handbook. The reader is asked to send anyefficacious and safe to use. comments to the Editor, Handbook of Pharmaceutical Excipients, While considerable efforts were made to ensure the accuracy of Royal Pharmaceutical Society of Great Britain, 1 Lambeth Highthe information presented in the Handbook, neither the publishers Street, London SE1 7JN, UK, or Editor, Handbook of Pharmaceu-nor the compilers can accept liability for any errors or omissions. In tical Excipients, American Pharmacists Association, 2215 Consti-particular, the inclusion of a supplier within the Suppliers Directory tution Avenue, NW, Washington, DC 20037-2985, USA. xiii
  • 13. International Steering CommitteeGregory E Amidon Bruce R KinseyUniversity of Michigan Ashland Aqualon Functional IngredientsAnn Arbor, MI, USA Harleysville, PA, USAGraham Buckton William J LambertUniversity of London Pacira Pharmaceuticals, Inc.London, UK San Diego, CA, USAColin G Cable Jian-Xin LiRoyal Pharmaceutical Society of Great Britain Evonik Degussa CorporationEdinburgh, UK Piscataway, NJ, USAWalter Cook Brian R MatthewsPfizer Global R & D Alcon Laboratories (UK) LtdKent, UK Hertfordshire, UKHenk J de Jong R Christian MoretonPuteaux, France FinnBrit Consulting Waltham, MA, USAStephen EdgeNovartis Pharma AG Gary MossBasel, Switzerland University of Hertfordshire Hertfordshire, UKRobert T ForbesUniversity of Bradford Marian E QuinnBradford, UK Royal Pharmaceutical Society of Great Britain London, UKJulian I Graubart Raymond C RoweAmerican Pharmacists Association Intelligensys LtdWashington, DC, USA Stokesley, UKRoger T Guest Niklas SandlerGlaxoSmithKline University of HelsinkiWare, Hertfordshire, UK Helsinki, FinlandBruno C Hancock Shirish A ShahPfizer Inc ICON Development SolutionsGroton, CT, USA Phoenix, AZ, USAKaren P Hapgood Catherine M SheehanMonash University United States PharmacopeiaClayton, Victoria, Australia Rockville, MD, USAStephen W Hoag Paul J SheskeyUniversity of Maryland at Baltimore The Dow Chemical CompanyBaltimore, MD, USA Midland, MI, USAJennifer C Hooton Kamalinder K SinghAstraZeneca SNDT Women’s UniversityCheshire, UK Mumbai, IndiaAnne Juppo Hirofumi TakeuchiUniversity of Helsinki Gifu Pharmaceutical UniversityHelsinki, Finland Gifu, JapanArthur H Kibbe Paul J WellerWilkes University School of Pharmacy Royal Pharmaceutical Society of Great BritainWilkes-Barre, PA, USA London, UKxiv
  • 14. Editorial StaffEditorial Staff of the Pharmaceutical PressRebecca GarnerMarian E QuinnJo WattsPaul J WellerProduction Staff of the Pharmaceutical PressTamsin CousinsSimon DuntonKarl ParsonsLinda PaulusJohn WilsonEditorial Staff of the American Pharmacists AssociationJulian I Graubart xv
  • 15. ContributorsO AbuBaker JH CollettGlaxoSmithKline Inc University of ManchesterKing of Prussia, PA, USA Manchester, UKKS Alexander W CookUniversity of Toledo Pfizer Global R&DToledo, OH, USA Kent, UKLV Allen Jr A CramInternational Journal of Pharmaceutical Compounding Pfizer Global R&DEdmond, OK, USA Kent, UKFA Alvarez-Nunez TC DahlAmgen Inc Gilead SciencesThousand Oaks, CA, USA Foster City, CA, USAGE Amidon PD DaugherityUniversity of Michigan Pfizer IncAnn Arbor, MI, USA Groton, CT, USAGP Andrews A DayThe Queen’s University of Belfast AstraZenecaBelfast, UK Macclesfield, Cheshire, UKNA Armstrong HJ de JongHarpenden, Hertfordshire, UK Puteaux, FranceTI Armstrong E DraganoiuWyeth Consumer Healthcare Lubrizol Advanced Materials IncHavant, Hampshire, UK Cleveland, OH, USAAC Bentham D DubashPfizer Global R&D Solvay Pharmaceuticals IncSandwich, Kent, UK Marietta, GA, USAM Bond S EdgeDanisco (UK) Ltd Novartis Pharma AGRedhill, Surrey, UK Basel, SwitzerlandMC Bonner C EggerUniversity of Bradford Rockwood PigmentsBradford, UK Turin, ItalyCG Cable T FarrellRoyal Pharmaceutical Society of Great Britain Colorcon IncEdinburgh, UK West Point, PA, USAAM Campeta RA FerrainaPfizer Inc Pfizer Global R&DGroton, CT, USA Groton, CT, USAWG Chambliss RT ForbesUniversity of Mississippi University of BradfordUniversity, MS, USA Bradford, UKRK Chang SO FreersSupernus Pharmaceutical Inc Grain Processing CorporationRockville, MD, USA Muscatine, IA, USAR Chen B FritzschingPfizer Inc BENEO-Palatinit GmbHGroton, CT, USA Mannheim, Germanyxvi
  • 16. Contributors xviiGP Frunzi P HoppuTime-Cap Labs Inc University of HelsinkiFarmingdale, NY, USA Helsinki, FinlandLY Galichet WL HulseLondon, UK University of Bradford Bradford, UKPL GogginPfizer Global R&D JT IrwinKent, UK Perrigo Company Allegan, MI, USAS GoldAstraZeneca M IsrebMacclesfield, Cheshire, UK University of Bradford Bradford, UKSR GoskondaSunnyvale, CA, USA H Ito NOF CorporationRT GuestGlaxoSmithKline Hyogo-ken, JapanWare, Hertfordshire, UK BR JastiRT Gupta University of the PacificSNDT Women’s University Stockton, CA, USAMumbai, India BA JohnsonVK Gupta Pfizer IncCovidien Groton, CT, USAWebster Groves, MO, USA DS JonesA Guy The Queen’s University BelfastBalchem Encapsulates Belfast, UKNew Hampton, NY, USA M JulienS Haley Gattefosse SASAstraZeneca Saint-Priest, FranceMacclesfield, Cheshire, UK MA KabirBC Hancock Schering-Plough Consumer HealthcarePfizer Inc Memphis, TN, USAGroton, CT, USA JS KaergerBA Hanson Aeropharm GmbHSchering-Plough Research Institute Rudolstadt, GermanySummit, NJ, USA AS KearneyKP Hapgood GlaxoSmithKline IncMonash University King of Prussia, PA, USAClayton, Victoria, Australia VL KettO Hausler ¨ The Queen’s University of BelfastRoquette Europe Belfast, UKLestrem, FranceX He AH KibbeGlaxoSmithKline Wilkes University School of PharmacyResearch Triangle Park, NC, USA Wilkes-Barre, PA, USASL Hem PB KlepakPurdue University Reheis IncWest Lafayette, IN, USA Berkeley Heights, NJ, USAL Hendricks DD LadipoInnophos Inc Pfizer Global R&DCranbury, NJ, USA Groton, CT, USAJC Hooton WJ LambertAstraZeneca Pacira Pharmaceuticals IncMacclesfield, Cheshire, UK San Diego, CA, USA
  • 17. xviii ContributorsBA Langdon C MrozPfizer Global R&D Colorcon LtdGroton, CT, USA Dartford, Kent, UKD Law MP MullarneyAbbott Laboratories Pfizer IncNorth Chicago, IL, USA Groton, CT, USAMG Lee K MurakamiMHRA Tomita Pharmaceutical Co LtdLondon, UK Tokushima-ken, JapanCS Leopold S MurdandeUniversity of Hamburg Pfizer IncHamburg, Germany Groton, CT, USA BJ MurphyX Li Pfizer IncUniversity of the Pacific Groton, CT, USAStockton, CA, USA RG NauseEB Lindblad Pfizer IncBrenntag Biosector Groton, CT, USAFrederikssund, Denmark S NemaO Luhn Pfizer Global R&DBENEO-Palatinit GmbH Chesterfield, MO, USAMannheim, Germany S ObaraPE Luner Shin-Etsu Chemical Co. LtdPfizer Inc Niigata, JapanGroton, CT, USA A PalmieriBR Matthews University of FloridaAlcon Laboratories (UK) Ltd Gainesville, FL, USAHertfordshire, UK MA PellettJS Maximilien Wyeth Consumer HealthcarePfizer Global R&D Havant, Hampshire, UKKent, UK L PeltonenCP McCoy University of HelsinkiThe Queen’s University of Belfast Helsinki, FinlandBelfast, UK Y PengC Medina AstraZeneca PharmaceuticalsAmgen Inc Wilmington, DE, USAThousand Oaks, CA, USA M PenningR Milallos Mainz, GermanyUniversity of Toledo JD PipkinToledo, OH, USA CyDex Pharmaceuticals Inc Lenexa, KS, USAMA MitchellPfizer Inc P PlumbSt Louis, MO, USA AstraZeneca Macclesfield, Cheshire, UKRC MoretonFinnBrit Consulting F PodczeckWaltham, MA, USA Tyne and Wear, UKGL Mosher P PopleVerrow Pharmaceuticals Inc SNDT Women’s UniversityLenexa, KS, USA Mumbai, IndiaG Moss W QuUniversity of Hertfordshire University of TennesseeHertfordshire, UK Memphis, TN, USA
  • 18. Contributors xixME Quinn N SeidoRoyal Pharmaceutical Society of Great Britain Takasago International CorporationLondon, UK Tokyo, JapanA Rajabi-Siahboomi HC ShahColorcon Inc SNDT Women’s UniversityWest Point, PA, USA Mumbai, IndiaRD Reddy SA ShahPfizer Inc ICON Development SolutionsGroton, CT, USA Phoenix, AZ, USAJP Reo U ShahSchering-Plough Consumer Healthcare Solvay Pharmaceuticals IncMemphis, TN, USA Marietta, GA, USAMA Repka RM ShankerUniversity of Mississippi Pfizer IncUniversity, MS, USA Groton, CT, USAB Richard JJ ShengPacira Pharmaceuticals Inc AstraZenecaSan Diego, CA, USA Wilmington, DE, USATL Rogers PJ SheskeyThe Dow Chemical Co The Dow Chemical CompanyBomlitz, Germany Midland, MI, USARC Rowe AJ ShuklaIntelligensys Ltd University of TennesseeStokesley, UK Memphis, TN, USAT Sakurai J ShurUeno Fine Chemicals Industry Ltd University of BathOsaka-shi, Japan Bath, UKN Sandler D SimonUniversity of Helsinki Roquette Freres `Helsinki, Finland Lestrem, FranceB Sarsfield A SinghBristol-Myers Squibb University of MississippiNew Brunswick, NJ, USA MS, USAM Savolainen KK SinghUniversity of Copenhagen SNDT Women’s UniversityCopenhagen, Denmark Mumbai, IndiaA Schoch JLP SohBENEO-Palatinit GmbH Pfizer Global R&DMannheim, Germany Kent, UKDR Schoneker RA StoreyColorcon Inc AstraZenecaWest Point, PA, USA Macclesfield, Cheshire, UKJ Schrier C SunPacira Pharmaceuticals Inc University of Minnesota College of PharmacySan Diego, CA, USA Minneapolis, MN, USACJ Sciarra AK TaylorSciarra Laboratories Baton RougeHickesville, NY, USA LA, USAJJ Sciarra J TeckoeSciarra Laboratories Colorcon LtdHickesville, NY, USA Dartford, Kent, UK
  • 19. xx About the EditorsMS Tesconi HM UnvalaWyeth Research Bayer CorpPearl River, NY, USA Myerstown, PA, USAD Thassu D WallickUCB Pharma Inc The Dow Chemical CompanyRochester, NY, USA Midland, MI, USAF Tian PJ WellerUniversity of Copenhagen Royal Pharmaceutical Society of Great BritainCopenhagen, Denmark London, UKS Tiwari P YingColorcon Inc Pacira Pharmaceuticals IncWest Point, PA, USA San Diego, CA, USAN TrivediCovidien PM YoungWebster Groves, MO, USA University of Sydney Sydney, NSW, AustraliaBF TruittBilcare Inc D ZhangPheonixville, PA, USA Merck Co Inc Rahway, NJ, USACK TyePfizer IncGroton, CT, USAAbout the EditorsRaymond C Rowe the Dow-Wolff Cellulosics R&D Group at The Dow Chemical Company in Midland, Michigan, USA. Paul received his BSc degreeBPharm, PhD, DSC, FRPharmS, FRSC, CPhys, MInstP in pharmacy from Ferris State University. Previously, he has workedRaymond Rowe has been involved in the Handbook of Pharma- as a research pharmacist in the area of solid dosage formceutical Excipients since the first edition was published in 1986, development at the Perrigo Company and the Upjohn (Pfizer)initially as an author then as a Steering Committee member. In Company. Paul has authored numerous journal articles in the areaaddition to his position as Chief Scientist at Intelligensys, UK, he is of pharmaceutical technology. He is a member of the AAPS and thealso Professor of Industrial Pharmaceutics at the School of Controlled Release Society.Pharmacy, University of Bradford, UK. He was formerly SeniorPrincipal Scientist at AstraZeneca, UK. In 1998 he was awarded the Marian E QuinnChiroscience Industrial Achievement Award, and in 1999 he wasthe British Pharmaceutical Conference Science Chairman. He has BSc, MSccontributed to over 350 publications in the pharmaceutical sciences Marian Quinn joined the publications department of the Royalincluding a book and eight patents. Pharmaceutical Society of Great Britain in 2007 for the sixth edition of the Handbook of Pharmaceutical Excipients, having previouslyPaul J Sheskey worked on the 34th and 35th editions of Martindale: The Complete Drug Reference. She has also previously worked at the NationalBSc, RPh Institute for Medical Research, Blackwell Publishing, and Elsevier.Paul Sheskey has been involved in the Handbook of Pharmaceutical Marian received her BSc (Hons) degree in microbiology from theExcipients as an author and member of the Steering Committee University of Surrey, and her MSc in molecular genetics from thesince the third edition. He is an Application Development Leader in University of Leicester.
  • 20. New MonographsThe following new monographs have been added to the Handbook of Pharmaceutical Excipients, 6th edition.Adipic Acid Maleic AcidAmmonium Chloride MethionineButylene Glycol Myristyl AlcoholCalcium Acetate NeotameCalcium Chloride Pentetic AcidCalcium Hydroxide PhospholipidsCalcium Lactate Poly(DL-Lactic Acid)Calcium Silicate PolyoxylglyceridesCellulose, Microcrystalline and Carboxymethylcellulose Sodium Potassium AlumCeresin Propylparaben SodiumCoconut Oil Safflower OilCorn Starch and Pregelatinized Starch Sodium CarbonateGlycine Sodium Formaldehyde SulfoxylateHydrophobic Colloidal Silica Sodium ThiosulfateHydroxypropyl Betadex Sucrose OctaacetateLactose, Inhalation Sulfur DioxideLactose, Monohydrate and Corn Starch TagatoseLactose, Monohydrate and Microcrystalline Cellulose TricaprylinLactose, Monohydrate and Povidone TrioleinLactose, Monohydrate and Powdered Cellulose Vitamin E Polyethylene Glycol Succinate xxi
  • 21. Related SubstancesAcetic acid see Acetic Acid, Glacial Dilute sulfuric acid see Sulfuric AcidActivated attapulgite see Attapulgite Dimethyl-b-cyclodextrin see CyclodextrinsAleuritic acid see Shellac Dioctyl phthalate see Dibutyl Phthalated-Alpha tocopherol see Alpha Tocopherol Dipotassium edetate see Edetic Acidd-Alpha tocopheryl acetate see Alpha Tocopherol Docusate calcium see Docusate Sodiumdl-Alpha tocopheryl acetate see Alpha Tocopherol Docusate potassium see Docusate Sodiumd-Alpha tocopheryl acid succinate see Alpha Tocopherol Dodecyl gallate see Propyl Gallatedl-Alpha tocopheryl acid succinate see Alpha Tocopherol Dodecyltrimethylammonium bromide see CetrimideAluminum distearate see Aluminum Monostearate Edetate calcium disodium see Edetic AcidAluminum tristearate see Aluminum Monostearate Eglumine see MeglumineAnhydrous citric acid see Citric Acid Monohydrate Ethyl gallate see Propyl GallateAnhydrous sodium citrate see Sodium Citrate Dihydrate Ethyl linoleate see Linoleic AcidAnhydrous sodium propionate see Sodium Propionate Ethylene glycol monopalmitate see Ethylene Glycol StearatesAqueous shellac solution see Shellac Ethylene glycol monostearate see Ethylene Glycol StearatesArtificial vinegar see Acetic Acid, Glacial Ethylparaben potassium see EthylparabenAspartame acesulfame see Aspartame Ethylparaben sodium see EthylparabenBacteriostatic water for injection see Water Extra virgin olive oil see Olive OilBentonite magma see Bentonite Fine virgin olive oil see Olive OilBeta tocopherol see Alpha Tocopherol Fuming sulfuric acid see Sulfuric AcidBeta-carotene see Coloring Agents Gamma tocopherol see Alpha Tocopheroln-Butyl lactate see Ethyl Lactate Glyceryl triisooctanoate see TricaprylinButylparaben sodium see Butylparaben Glycine hydrochloride see GlycineCalcium acetate monohydrate see Calcium Acetate Hard water see WaterCalcium ascorbate see Sodium Ascorbate Hesperidin see Neohesperidin DihydrochalconeCalcium cyclamate see Sodium Cyclamate Hexadecyltrimethylammonium bromide see CetrimideCalcium diorthosilicate see Calcium Silicate High-fructose syrup see FructoseCalcium polycarbophil see Polycarbophil Hyaluronic acid see Sodium HyaluronateCalcium propionate see Sodium Propionate Hydrogenated lanolin see LanolinCalcium sorbate see Sorbic Acid Hydrogenated vegetable oil, type II see Vegetable Oil, Hydro-Calcium sulfate hemihydrate see Calcium Sulfate genatedCalcium trisilicate see Calcium Silicate 2-Hydroxyethyl-b-cyclodextrin see CyclodextrinsCalcium trisodium pentetate see Pentetic Acid 3-Hydroxypropyl-b-cyclodextrin see Hydroxypropyl BetadexCapric acid see Lauric Acid Indigo carmine see Coloring AgentsCarbon dioxide-free water see Water Invert sugar see SucroseCationic emulsifying wax see Wax, Nonionic Emulsifying Isotrehalose see TrehaloseCeratonia extract see Ceratonia Laccaic acid B see ShellacCetylpyridinium bromide see Cetylpyridinium Chloride Lampante virgin olive oil see Olive OilChlorhexidine acetate see Chlorhexidine Lanolin alcohols ointment see Petrolatum and Lanolin AlcoholsChlorhexidine gluconate see Chlorhexidine DL-Leucine see LeucineChlorhexidine hydrochloride see Chlorhexidine Liquefied phenol see PhenolChlorodifluoromethane see Chlorodifluoroethane (HCFC) Liquid fructose see FructoseChlorophenoxyethanol see Phenoxyethanol Magnesium carbonate anhydrous see Magnesium CarbonateCorn syrup solids see Maltodextrin Magnesium carbonate hydroxide see Magnesium Carbonatem-Cresol see Cresol Magnesium lauryl sulfate see Sodium Lauryl Sulfateo-Cresol see Cresol Magnesium metasilicate see Magnesium Silicatep-Cresol see Cresol Magnesium orthosilicate see Magnesium SilicateCrude olive-pomace oil see Olive Oil Magnesium trisilicate anhydrous see Magnesium TrisilicateCyclamic acid see Sodium Cyclamate D-Malic acid see Malic AcidDe-aerated water see Water L-Malic acid see Malic AcidDehydrated alcohol see Alcohol d-Menthol see MentholDelta tocopherol see Alpha Tocopherol l-Menthol see MentholDenatured alcohol see Alcohol D-Methionine see MethionineDextrose anhydrous see Dextrose DL-Methionine see MethionineDiazolidinyl urea see Imidurea Methyl lactate see Ethyl LactateDibasic potassium phosphate see Sodium Phosphate, Dibasic Methyl linoleate see Linoleic AcidDiethylene glycol monopalmitostearate see Ethylene Glycol Stea- Methyl methacrylate see Polymethacrylates rates Methyl oleate see Ethyl OleateDilute acetic acid see Acetic Acid, Glacial Methylparaben potassium see MethylparabenDilute alcohol see Alcohol Methylparaben sodium see MethylparabenDilute ammonia solution see Ammonia Solution N-Methylpyrrolidone see PyrrolidoneDilute hydrochloric acid see Hydrochloric Acid Microcrystalline cellulose and carrageenan see Cellulose, Micro-Dilute phosphoric acid see Phosphoric Acid crystallinexxii
  • 22. Related Substances xxiiiMicrocrystalline cellulose and guar gum see Cellulose, Microcrys- Sodium borate anhydrous see Sodium Borate talline Sodium carbonate decahydrate see Sodium CarbonateMicrocrystalline cellulose spheres see Sugar Spheres Sodium carbonate monohydrate see Sodium CarbonateModified lanolin see Lanolin Sodium edetate see Edetic AcidMonobasic potassium phosphate see Sodium Phosphate, Mono- Sodium erythorbate see Erythorbic Acid basic Sodium glycinate see GlycineMontmorillonite see Magnesium Aluminum Silicate Sodium laurate see Lauric AcidNeotrehalose see Trehalose Sodium myristate see Myristic AcidNormal magnesium carbonate see Magnesium Carbonate Sodium palmitate see Palmitic AcidNPTAB see Sugar Spheres Sodium sorbate see Sorbic AcidOctyl gallate see Propyl Gallate Sodium sulfite heptahydrate see Sodium SulfiteOleyl oleate see Oleyl Alcohol Soft water see WaterOlive-pomace oil see Olive Oil Spermaceti wax see Wax, Cetyl EstersPalmitin see Palmitic Acid Stearalkonium hectorite see HectoritePentasodium pentetate see Pentetic Acid Sterile water for inhalation see WaterPharmaceutical glaze see Shellac Sterile water for injection see WaterPhenoxypropanol see Phenoxyethanol Sterile water for irrigation see WaterPolacrilin see Polacrilin Potassium Sugartab see Sugar, CompressiblePoly(methyl methacrylate) see Polymethacrylates Sunset yellow FCF see Coloring AgentsPotassium bisulfite see Potassium Metabisulfite Synthetic paraffin see ParaffinPotassium myristate see Myristic Acid DL-Tagatose see TagatosePotassium propionate see Sodium Propionate L-Tagatose see TagatosePowdered fructose see FructosePropan-1-ol see Isopropyl Alcohol Tartrazine see Coloring Agents(S)-Propylene carbonate see Propylene Carbonate Theobroma oil see Suppository Bases, Hard FatPropylparaben potassium see Propylparaben Tocopherols excipient see Alpha TocopherolPurified bentonite see Bentonite Tribasic sodium phosphate see Sodium Phosphate, DibasicPurified stearic acid see Stearic Acid Trimethyl-b-cyclodextrin see CyclodextrinsQuaternium 18-hectorite see Hectorite Trimethyltetradecylammonium bromide see CetrimideRapeseed oil see Canola Oil Trisodium edetate see Edetic AcidRefined almond oil see Almond Oil Virgin olive oil see Olive OilRefined olive-pomace oil see Olive Oil Water for injection see WaterSaccharin ammonium see Saccharin White petrolatum see PetrolatumSaccharin calcium see Saccharin Zinc formaldehyde sulfoxylate see Sodium Formaldehyde Sulfox-Safflower glycerides see Safflower Oil ylateSelf-emulsifying glyceryl monostearate see Glyceryl Monostearate Zinc propionate see Sodium PropionateSodium bisulfite see Sodium Metabisulfite Zinc trisodium pentetate see Pentetic Acid
  • 23. BibliographyA selection of publications and websites which contain useful information on pharmaceutical excipients is listed below:Ash M, Ash I. Handbook of Pharmaceutical Additives, 3rd edn, Kemper FH, et al. Blue List Cosmetic Ingredients, Aulendorf, Endicott, NY: Synapse Information Resources, 2007. Germany: Editio Cantor, 2000.Aulton ME. Aulton’s Pharmaceutics: The Design and Manufacture Lewis RJ. Sax’s Dangerous Properties of Industrial Materials, 11th of Medicines, 3rd edn, Edinburgh: Churchill Livingstone, 2007. edn, New York: John Wiley, 2004.Banker GS. Rhodes CT. Modern Pharmaceutics, 4th edn, New Lund W. The Pharmaceutical Codex: Principles and Practice of York: Marcel Dekker, 2002. Pharmaceutics, 12th edn, London: Pharmaceutical Press, 1994.British Pharmacopoeia 2009, London: The Stationery Office, 2009. Matthews BR. Pharmaceutical Excipients: A Manufacturer’s Hand-Bugay DE, Findlay WP. Pharmaceutical Excipients Characteriza- book, Bethesda, MD: PDA Books, 2005. tion by IR, Raman, and NMR Spectroscopy, New York: Marcel National Library of Medicine. TOXNET. http://toxnet.nlm.nih.gov Dekker, 1999. (accessed 5 February 2009).European Pharmacopoeia, 6th edn, Strasbourg: Council of Europe, O’Neil MJ, et al. The Merck Index: an Encyclopedia of Chemicals, 2008. Drugs, and Biologicals, 14th edn, Whitehouse Station, NJ:Florence AT. Salole EG. Formulation Factors in Adverse Reactions, Merck, 2006. London: Butterworth, 1990. Smolinske SC. Handbook of Food, Drug and Cosmetic Excipients,Food and Drug Administration. Inactive Ingredients Database. Boca Raton, FL: CRC Press, 1992. http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm Swarbrick J. Boylan JC. Encyclopedia of Pharmaceutical Technol- (accessed 5 February 2009). ogy, 2nd edn, New York: Marcel Dekker, 2002.Food Chemicals Codex, 6th edn, Bethesda, MD: United States Sweetman SC. Martindale: the Complete Drug Reference, 36th edn, Pharmacopeia, 2008. London: Pharmaceutical Press, 2009.Health and Safety Executive. EH40/2005: Workplace Exposure United States Pharmacopeia 32 and National Formulary 27, Limits. Sudbury: HSE Books, 2005 (updated 2007). http:// Rockville, MD: United States Pharmacopeial Convention, 2009. www.hse.gov.uk/coshh/table1.pdf (accessed 5 February 2009). University of the Sciences in Philadelphia, Remington: the ScienceHealth Canada. Canadian List of Acceptable Non-medicinal and Practice of Pharmacy, 21st edn, Baltimore: Lippincott Ingredients. http://www.hc-sc.gc.ca/dhp-mps/prodnatur/legisla- Williams and Wilkins, 2005. tion/docs/nmi-imn_list1-eng.php (accessed 5 February 2009). Weiner M, Bernstein IL. Adverse Reactions to Drug FormulationHoepfner E, et al. Fiedler Encyclopedia of Excipients for Agents: A Handbook of Excipients, New York: Marcel Dekker, Pharmaceuticals, Cosmetics and Related Areas, Aulendorf, 1989. Germany: Editio Cantor, 2002. Weiner ML. Kotkoskie LA. Excipient Toxicity and Safety, NewJapan Pharmaceutical Excipients Council, Japanese Pharmaceutical York: Marcel Dekker, 2000. Excipients 2004, Tokyo: Yakuji Nippo, 2004.Japanese Pharmacopeia, 15th edn, Tokyo: Yakuji Nippo, 2006.xxiv
  • 24. AbbreviationsSome units, terms, and symbols are not included in this list as they are defined in the text. Common abbreviations have been omitted. Thetitles of journals are abbreviated according to the general style of the Index Medicus.% approximately. IV intravenous.Ad Addendum. J joule(s).ADI acceptable daily intake. JP Japanese Pharmacopeia.approx approximately. JPE Japanese Pharmaceutical Excipientsatm atmosphere. kcal kilocalorie(s).BAN British Approved Name. kg kilogram(s).bp boiling point. kJ kilojoule(s).BP British Pharmacopoeia. kPa kilopascal(s).BS British Standard (specification). L liter(s).BSI British Standards Institution. LAL Limulus amoebocyte lysate.cal calorie(s). LC50 a concentration in air lethal to 50% of the specifiedCAS Chemical Abstract Service. animals on inhalation.CFC chlorofluorocarbon. LD50 a dose lethal to 50% of the specified animals orcfu colony-forming unit microorganisms.cm centimeter(s). LdLo lowest lethal dose for the specified animals orcm2 square centimeter(s). microorganisms.cm3 cubic centimeter(s). m meter(s).cmc critical micelle concentration. m2 square meter(s).CNS central nervous system. m3 cubic meter(s).cP centipoise(s). M molar.cSt centistoke(s). max maximum.CTFA Cosmetic, Toiletry, and Fragrance Association. MCA Medicines Control Agency (UK).d particle diameter (d10 at 10 percentile; d50 at 50 mg milligram(s). percentile; d90 at 90 percentile). MIC minimum inhibitory concentration.D&C designation applied in USA to dyes permitted for min minute(s) or minimum. use in drugs and cosmetics. mL milliliter(s).DoH Department of Health (UK). mm millimeter(s).DSC differential scanning calorimetry. mM millimolar.EC European Community. mm2 square millimeter(s).e.g. exemplit gratia, ‘for example’. mm3 cubic millimeter(s).EINECS European Inventory of Existing Commercial Che- mmHg millimeter(s) of mercury. mical Substances. mmol millimole(s).et al et alii, ‘and others’. mN millinewton(s).EU European Union. mol mole(s).FAO Food and Agriculture Organization of the United mp melting point. Nations. mPa millipascal(s).FAO/WHO Food and Agriculture Organization of the United MPa megapascal(s). Nations and the World Health Organization. mg microgram(s).FCC Food Chemicals Codex. mm micrometer(s).FDA Food and Drug Administration of the USA. N newton(s) or normal (concentration).FD&C designation applied in USA to dyes permitted for NIR near-infrared. use in foods, drugs, and cosmetics. nm nanometer(s).FFBE Flat face beveled edge. o/w oil-in-water.g gram(s). o/w/o oil-in-water-in-oil.GMP Good Manufacturing Practice. Pa pascal(s).GRAS generally recognized as safe by the Food and Drug pH the negative logarithm of the hydrogen ion con- Administration of the USA. centration.HC hydrocarbon. PhEur European Pharmacopeia.HCFC hydrochlorofluorocarbon. pKa the negative logarithm of the dissociation constant.HFC hydrofluorocarbon. pph parts per hundred.HIV human immunodeficiency virus. ppm parts per million.HLB hydrophilic–lipophilic balance. psia pounds per square inch absolute.HSE Health and Safety Executive (UK). R reflectance.i.e. id est, ‘that is’. RDA recommended dietary allowance (USA).IM intramuscular. rpm revolutions per minute.INN International Nonproprietary Name. s second(s).IP intraperitoneal. SC subcutaneous.ISO International Organization for Standardization. SEM scanning electron microscopy or scanning electronIU International Units. microphotograph. xx v
  • 25. xxvi AbbreviationsSI Statutory Instrument or Systeme International ` USP–NF The United States Pharmacopeia National Formu- d’Unites (International System of Units). lary.TDLo lowest toxic dose for the specified animals or UV ultraviolet. microorganisms. v/v volume in volume.TPN total parental nutrition. v/w volume in weight.TWA time weighted average. WHO World Health Organization.UK United Kingdom. w/o water-in-oil.US or USA United States of America. w/o/w water-in-oil-in-water.USAN United States Adopted Name. w/v weight in volume.USP The United States Pharmacopeia. w/w weight in weight.
  • 26. Units of MeasurementThe information below shows imperial to SI unit conversions for the 1 millimeter of mercury (mmHg) = 133.322 pascals (Pa)units of measurement most commonly used in the Handbook. SI 1 pound per square inch (psi) = 6894.76 pascals (Pa)units are used throughout with, where appropriate, imperial unitsreported in parentheses. Surface tensionArea 1 dyne per centimeter (dyne/cm) = 1 millinewton per meter (mN/m)1 square inch (in2) = 6.4516 Â 10–4 square meter (m2)1 square foot (ft2) = 9.29030 Â 10–2 square meter (m2)1 square yard (yd2) = 8.36127 Â 10–1 square meter (m2) Temperature Celsius (8C) = (1.8 Â 8C) þ 32 Fahrenheit (8F)Density Fahrenheit (8F) = (0.556 Â 8F) –17.8 Celsius (8C)1 pound per cubic foot (lb/ft3) = 16.0185 kilograms per cubic meter(kg/m3) Viscosity (dynamic)Energy 1 centipoise (cP) = 1 millipascal second (mPa s) 1 poise (P) = 0.1 pascal second (Pa s)1 kilocalorie (kcal) = 4.1840 Â 103 joules (J)Force Viscosity (kinematic)1 dyne (dynes) = 1 Â 10–5 newton (N) 1 centistoke (cSt) = 1 square millimeter per second (mm2/s)Length Volume ˚1 angstrom (A) = 10–10 meter (m) 1 cubic inch (in3) = 1.63871 Â 10–5 cubic meter (m3)1 inch (in) = 2.54 Â 10–2 meter (m) 1 cubic foot (ft3) = 2.83168 Â 10–2 cubic meter (m3)1 foot (ft) = 3.048 Â 10–1 meter (m) 1 cubic yard (yd3) = 7.64555 Â 10–1 cubic meter (m3)1 yard (yd) = 9.144 Â 10–1 meter (m) 1 pint (UK) = 5.68261 Â 10–4 cubic meter (m3) 1 pint (US) = 4.73176 Â 10–4 cubic meter (m3)Pressure 1 gallon (UK) = 4.54609 Â 10–3 cubic meter (m3)1 atmosphere (atm) = 0.101325 megapascal (MPa) 1 gallon (US) = 3.78541 Â 10–3 cubic meter (m3) xxvii
  • 27. A Acacia A1 Nonproprietar