Handbook of Pharmaceutical Additives Third Edition Handbook of Pharmaceutical Additives Third Edition Compiled by Michael and Irene Ash Synapse Information Resources © Synapse Information Resources, Inc. 2007, 2008 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by an means, electronic, mechanical, photocopying, recording, or otherwise without the prior permission of Synapse Information Resources, Inc. Published by Synapse Information Resources, Inc. 1247 Taft Ave. Endicott, NY 13760 Library of Congress Control Number: 2007922141 ISBN-13: 978-1-890595-93-7 ISBN-10: 1-890595-93-4 Printed in the U.S.A. Contents Preface ......................................................................................................................................................v Abbreviations .....................................................................................................................................vii Part I Trade Name Reference..............................................................................................15 Part II Chemical Component Cross-Reference.................................................................808 Part III Functional/Application Index................................................................................2260 Part IV Manufacturers Directory........................................................................................2608 Appendix .................................................................................................................................2761 CAS Number Index.................................................................................................2762 EINECS/ELINCS Number Index.............................................................................2853 FEMA Number Index..............................................................................................2910 Inactive Ingredient Guide: Approved Products...................................................2928 Inactive Ingredient Guide: Permanently Listed Color Additives.......................2965 USP and/or NF Compliant Chemicals...................................................................2968 BP Compliant Chemicals.......................................................................................2971 EP Compliant Chemicals.......................................................................................2975 Glossary..................................................................................................................2978 Bibliography...........................................................................................................2993 Preface The Handbook of Pharmaceutical Additives, Third Edition has been extensively updated from the previous edition which was published five years ago. This edition contains completely new trade name and generic chemical entries as well as added information for previously listed excipients. The new edition reflects the many changes in the manufacturers of both trade name and generic products. More than 5300 trade name products and 4000 generic chemicals and materials, available from worldwide manufacturers are described in this reference. Pharmaceutical additives are defined here as the secondary ingredients that are present in both prescription and over-the-counter drug formulations and contribute in one or more of the following ways: • improving consumption ease of the dosage form by masking unpleasant odor, improving palatibility or appearance of the active ingredient. • enabling or enhancing the delivery of the drug or medicine that is available in a variety of dosage forms (i.e., oral; topical, ophthalmic, and otic; suppositories; injectables; inhalants) and thus improving its efficacy, control of bioavailability, uniformity, and/or flow characteristics • increasing the stability of active ingredients. • acting as a filler or diluent so that an adequate amount of material is available to properly fill a dosage form. • acting as an antimicrobial or antioxidant to extend the shelf life of the active ingredient. Thus, the definition of pharmaceutical additives for the purpose of this book encompasses excipients, synergists, or chemicals that substantively contribute to the effectiveness of the active ingredient. Entries for both trade names and chemicals contain extensive information gathered from worldwide manufacturers, distributors, trade journals, government documents, and other reference sources. The Handbook of Pharmaceutical Additives, Third Edition centralizes and integrates information on these chemicals and materials thereby serving as an essential guide to pharmaceutical product managers, formulation scientists, quality controllers, ingredient chemists, pharmacists, physicians, and consumers. This reference contains the following sections: Part I Trade Name Reference contains over 5300 alphabetical entries of trade name pharmaceutical additive products with extensive profiles of each product listed. Part II Chemical Component Cross-Reference contains almost 4000 pharmaceutical chemicals/materials that are either contained in the trade name products profiled in Part I or are generic chemicals used as pharmaceutical additive ingredients. Each entry includes, wherever possible, its synonyms, CAS number, EINECS number/ELINCS, FEMA number, UN/DOT number, molecular and empirical formulas, chemical properties, functions and applications, toxicology, precautions, use levels, regulatory information, and manufacturers and distributors of the chemical. All chemical/material synonyms are cross-referenced back to the main entry. The chemical monograph entries also contain a listing of the trade name products that are either equivalent to the chemical entry or contain this chemical as one of its ingredients Part III Functional/Application Index is a powerful tool for locating the trade names and chemicals based on their function and application. By searching for key functional words related to pharmaceutical additives such as anticaking agents, binders, colorants, disintegrants, emulsifiers, encapsulants, fillers, flavors, gellants, in specific application areas such as tablets, capsules, inhalants, ointments, suppositories, etc., the user is directed to the trade names and/or chemicals that have that specific functional/application attribute. Part IV Manufacturers Directory contains detailed contact information for the more than 3000 worldwide manufacturers and their branches of trade name products and chemical components that are referenced in this handbook. Wherever possible, telephone, telefax, toll-free numbers, e-mail and internet addresses, and complete mailing addresses are included for each manufacturer. Appendixes CAS Number Index contains CAS number entries followed by a listing of their trade name product and chemical Handbook of Pharmaceutical Additives, Third Edition v Preface equivalents in alphabetical order. The chemical name is in boldfaced type. EINECS/ELINCS Number Index contains EINECS/ELINCS number entries followed by a listing of their trade name product and generic chemical equivalents in alphabetical order. The chemical name is in boldfaced type. FEMA Number Index orders chemicals (that have assigned FEMA numbers) contained in this reference by these numbers. These numbers have been assigned by the Flavor and Extract Manufacturers Association). Glossary contains definitions of terminology associated with the pharmaceutical industry. Chemicals in Compliance with Pharmaceutical Standards: Inactive Ingredient Guide: Approved Products Inactive Ingredient Guide: Permanently Listed Color Additives USP/NF Chemical Listing British Pharmacopoeia Chemical Listing European Pharmacopoeia Chemical Listing M. & I. Ash Handbook of Pharmaceutical Additives, Third Edition vi Abbreviations abs. absolute BGA Federal Republic of Germany Health ABS acrylonitrile-butadiene-styrene Dept. certification absorp. absorption BgVV Bundesinsititut fŸr Gesundheitlichen ACGIH American Conference of Verbraucherschutz und Governmental Industrial Hygienists VeterinŠrmedizin (Federal Institute for ACN acrylonitrile Consumer Health Protection and act. active Veterinary Medicine) (Germany) ADI acceptable daily intake (FAO/WHO) BHA butylated hydroxyanisole ADR adverse drug reactions BHT butylated hydroxytoluene AEL acceptable exposure limit biochem. biochemical adsorp. adsorption biodeg. biodegradable agric. agricultural bldg. building agrochem. agrochemical blk. black a.i. active ingredient BMC bulk molding compound AIHA American Industrial Hygiene BOD biochemical oxygen demand Association BP British Pharmacopeia alc. alcohol b.p. boiling point Am., Amer. American BR butadiene rubbers, polybutadienes amts. amounts B&R Ball & Ring anhyd. anhydrous br., brn. brown ANSI American National Standards Institute brnsh. brownish AOC assimilable organic carbon BS British Standards APHA American Public Health Association B/S butadiene/styrene API Active Pharmceutical Ingredients BSI British Standards Institute applic(s). application(s) BSS British Standard Sieve aq. aqueous Btu British thermal unit AS acrylonitrile-butadiene-styrene B.U. Brabender units (viscosity) ASA acrylic-styrene-acrylonitrile BVC British Veterinary Codex ASBC Am. Society of Brewing Chemists BVO brominated vegetable oil ASTM American Society for Testing and byprod. byproduct(s) Materials C degrees Centigrade ATH alumina trihydrate CAA Clean Air Act atm atmosphere CAB cellulose acetate butyrate at.wt. atomic weight calcd. calculated autoignit. autoignition cap. capillary aux(s). auxiliary, auxililaries CAS Chemical Abstracts Service avail. available CC closed cup avg. average cc cubic centimeter(s) a.w. atomic weight CCFAC Codex Committee on Food Additives BAC biological activated carbon and Contaminants BATF Bureau of Alcohol, Tobacco, and CCl carbon tetrachloride 4 Firearms (U.S.) CD completely denatured BDG butyl diglycol CDA completely denatured alcohol BDOC biodegradable dissolved organic CEL corporate exposure limit carbon CERCLA Comprehensive Environmental BfArM Bundesinstitut fŸr Arzneimittel und Response, Compensation, & Liability Medizinprodukte (Federal Institute for Act (U.S.) Drugs and Medical Devices, CFC chlorofluorocarbon Germany) CFN Council on Food & Nutrition (Am. Medical Assoc.) Handbook of Pharmaceutical Additives, Third Edition vii Abbreviations CFR Code of Federal Regulations (U.S.) DEA diethanolamide, diethanolamine cfu colony-forming units dec. decomposes cGMP current good manufacturing practice decomp. decomposition (U.S. FDA) DEG diethylene glycol ch. Chapter deliq. deliquescent char. characteristic, characterized dens. density chel. chelation deriv(s). derivative(s) chem(s). chemical(s) descrip. description CI Color Index dg decigram(s) CIIR chlorobutyl rubber DI deionized CIR Cosmetic Ingredient Review diam. diameter cks centistoke(s) dielec. dielectric cl clear dil. dilute CL ceiling concentration DIN Deutsches Institut fuer Normung cm centimeter(s) (German Standards Organization) cm3 cubic centimeter(s) disp. dispersible, dispersion CMC carboxymethylcellulose dissip. dissipation CMC critical Micelle concentration dist. distilled c.m.p. capillary melting point distort. distortion CNS central nervous system distrib. distributor CO carbon monoxide dk. dark COC Cleveland Open Cup DMF dimethyl formamide COD chemical oxygen demand DMF Drug Master Files coeff. coefficient DO dissolved oxygen COF coefficient of friction D.O. dissolved oxygen compat. compatible DOC dissolved organic carbon compd(s). compound(s) DOM dissolved organic matter compr. compression DOP dioctyl phthalate conc(s). concentrated, concentration(s) DOT Department of Transportation (U.S.) conduct. Conductive, conductivity DPG diphenyl guanidine, dipropylene glycol const. constant DSB dry solids basis contg. containing DSI Canadian Provisional Domestic cosolv. cosolvent Substance list CP Canadian Pharmacopeia DTUL deflection temperature under load cp centipoise(s) DVB divinylbenzene CPE chlorinated polyethylene DW distilled water, deionized water cps centipoise(s) DWV drainage, waste and vent CPVC chlorinated polyvinyl chloride eb, EB electron beam CR chloroprene rubber, polychloroprene EC European Community cryst. crystalline, crystallization EC50 environmental concentration, 50% cs centistoke(s) EDTA ethylenediamine tetraacetic acid cSt centistoke(s) EE epoxy equivalent CTFA Cosmetic, Toiletry and Fragrance EEC European Economic Community Association EED environmental endocrine disrupter ctks centistoke(s) EEW epoxide equivalent weight CWA Clean Water Act e.g. for example cwt hundred weight EGC Epoxide Group Content DAB Deutsche. Arzneibuch (German EINECS European Inventory of Existing Pharmacopoeia) Commercial Chemical Substances DAC Deutscher Arneimittel Codex (German elec. electrical Pharmacopoeia Codex) ELINCS European List of Notified Chemical D&C Drugs & Cosmetics Substances dc direct current elong. elongation DE dextrose equivalent EMI electromagnetic interference Handbook of Pharmaceutical Additives, Third Edition viii Abbreviations EMS electromagnetic shielding g gram(s) ENB 5-ethylidene-2-norbornene gal gallon(s) EO ethylene oxide g/d gram/dyne EP European Pharmacopoeia GFRP glass fiber-reinforced plastic EP extreme pressure G-H Gardner-Holdt EPA Environmental Protection Agency GI gastro-intestinal (U.S.) glac. glacial EPDM ethylene-propylene-diene rubber, GLP good laboratory practice ethylene-propylene terpolymer GLY glycine EPR ethylene-propylene rubber GMP good manufacturing practice EPS expandable polystyrene gpd gallons per day equip. equipment gpm gallons per minute equiv. equivalent GPPS general purpose polystyrene ESCR environmental stress crack resistance gpt gallons per ton ESD electrostatic discharge gr. gravity ESO epoxidized soybean oil gran. granules, granular ESP electrostatic protection GRAS generally regarded as safe esp. especially grn(sh). green. greenish EU European Union GRP glass-reinforced plastics, glass- Eur.Ph. European Pharmacopeia reinforced polyester EVA ethylene vinyl acetate GVS Gardner varnish scale (color) evap. Evaporation GWP Global warming potential exc. excellent h hour(s) F degrees Fahrenheit HAF high abrasion furnace carbon black FA fatty acid HALS hindered amine light stabilizer FAO Food and Agriculture Organization HAP hazardous air pollutant (United Nations) HAPS hazardous air pollutants FAP Food Additive Petition (U.S.) HAP's hazardous air pollutants FCC Food Chemicals Codex HB horizontal burning FCC fluorochlorocarbon HC hydrocarbon FDA Food and Drug Administration (U.S.) HCFC hydrochlorofluorocarbon FD&C Foods, Drugs, and Cosmetics HCl hydrochloride, hydrochloric acid FEMA Flavor and Extract Manufacturers’ HDPE high-density polyethylene Association (U.S.) HDT heat distortion (deflection) temp. FEP fluorinated ethylene propylene HFC hydrofluorocarbon FFA free fatty acid Hg mercury FFDCA Federal Food, Drug, and Cosmetic Act HIPS high-impact polystyrene FG food grade HLB hydrophilic lipophilic balance FIFRA Federal Insecticide, Fungicide, and HMIS Hazardous Material Identification Rodenticide Act (U.S. EPA) System FKM fluoroelastomer hr hour(s) fl fluid HTST high temperature short-time flamm. flammable, flammability pasteurization flex. flexural HEUR hydrophobically modified ethoxylate FNB Food and Nutrition Board urethane f.p. freezing point HVAC heating, ventilation, air conditioning FP French Pharmacopoeia HVP hydrolyzed vegetable protein FR flame retardant hyd. hydroxyl FR-ABS flame retardant ABS hydrog. hydrogenated FRP fiberglass-reinforced plastics Hz hertz F-T Fischer-Tropsch IARC International Agency for Research on ft foot, feet Cancer (United Nations) f.w. formula weight i.b.p. initial boiling point G giga Handbook of Pharmaceutical Additives, Third Edition ix