Handbook of
`Pharmaceutical
`Excipients
`Fifth Edition
`
`Edited by
`Raymond C Rowe, Paul J Sheskey
`and Siân C Owen
`
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`

`Handbook of
`Pharmaceutical Excipients
`
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`

`Handbook of
`Pharmaceutical Excipients
`
`F I F T H E D I T I O N
`
`Edited by
`
`Raymond C Rowe
`BPharm, PhD, DSc, FRPharmS, CChem,
`
`FRSC, CPhys, MInstP
`
`Chief Scientist
`Intelligensys Ltd
`Billingham, UK
`
`Paul J Sheskey
`BSc, RPh
`
`Technical Services Leader
`The Dow Chemical Company
`Midland
`MI, USA
`
`Siaˆn C Owen
`BSc, MA
`
`Development Editor
`Royal Pharmaceutical Society of Great Britain
`London, UK
`
`London . Chicago
`
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`Published by the Pharmaceutical Press
`Publications division of the Royal Pharmaceutical Society of Great Britain
`
`1 Lambeth High Street, London SE1 7JN, UK
`100 South Atkinson Road, Suite 206, Grayslake, IL 60030-7820, USA
`
`and the American Pharmacists Association
`2215 Constitution Avenue, NW, Washington, DC 20037-2985, USA
`
`# Pharmaceutical Press and American Pharmacists Association 2006
`
`is a trademark of Pharmaceutical Press
`
`First published 1986
`Second edition published 1994
`Third edition published 2000
`Fourth edition published 2003
`Fifth edition published 2006
`
`Printed in Great Britain by Butler & Tanner, Frome, Somerset
`Typeset by Data Standards Ltd, Frome, Somerset
`
`ISBN 0 85369 618 7 (UK)
`ISBN 1 58212 058 7 (USA)
`
`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.
`
`A catalogue record for this book is available from the British Library
`
`Library of Congress Cataloging-in-Publication Data
`Handbook of pharmaceutical excipients.–5th ed. / edited by Raymond C.
`Rowe, Paul J. Sheskey, Siaˆ n C. Owen.
`p. ; cm.
`Includes bibliographical references and index.
`ISBN 1-58212-058-7 (USA) – ISBN 0-85369-618-7 (UK)
`1. Excipients–Handbooks, manuals, etc.
`[DNLM: 1. Excipients–Handbooks. 2. Technology, Pharmaceutical–Handbooks.
`QV 735 H236 2006] I. Rowe, Raymond C. II. Sheskey, Paul J. III. Owen, Siaˆ n C.
`IV. American Pharmacists Association.
`
`RS201.E87H36 2006
`0
`.19–dc22
`615
`
`2005028523
`
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`Contents
`
`International Steering Committee ix
`Editorial Staff
`ix
`x
`Contributors
`About the Editors
`New Monographs
`Related Substances
`Preface xvi
`xvii
`Arrangement
`Acknowledgments
`Notice to Readers
`Bibliography
`xx
`Abbreviations
`xx
`Units of Measurement
`
`xii
`xiii
`xiv
`
`xix
`xix
`
`xxii
`
`Monographs
`
`Acacia
`Acesulfame Potassium
`Acetic Acid, Glacial
`Acetone
`Acetyltributyl Citrate
`Acetyltriethyl Citrate
`Agar
`Albumin
`Alcohol
`Alginic Acid
`Aliphatic Polyesters
`Alitame
`Almond Oil
`Alpha Tocopherol
`Aluminum Hydroxide Adjuvant
`Aluminum Oxide
`Aluminum Phosphate Adjuvant
`Aluminum Stearate
`Ammonia Solution
`Ammonium Alginate
`Ascorbic Acid
`
`Ascorbyl Palmitate
`Aspartame
`Attapulgite
`Bentonite
`Benzalkonium Chloride
`Benzethonium Chloride
`Benzoic Acid
`Benzyl Alcohol
`Benzyl Benzoate
`Boric Acid
`Bronopol
`Butylated Hydroxyanisole
`Butylated Hydroxytoluene
`Butylparaben
`Calcium Alginate
`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
`Castor Oil, Hydrogenated
`Cellulose, Microcrystalline
`Cellulose, Powdered
`Cellulose, Silicified Microcrystalline
`Cellulose Acetate
`Cellulose Acetate Phthalate
`Ceratonia
`Cetostearyl Alcohol
`
`1
`4
`6
`8
`10
`12
`14
`16
`18
`21
`24
`28
`30
`32
`36
`38
`40
`42
`44
`46
`48
`
`51
`53
`56
`58
`61
`64
`66
`69
`72
`74
`76
`79
`81
`83
`86
`89
`93
`96
`100
`102
`105
`108
`111
`116
`118
`120
`124
`128
`130
`132
`136
`139
`142
`145
`148
`150
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`vi
`
`Contents
`
`Cetrimide
`Cetyl Alcohol
`Cetylpyridinium Chloride
`Chitosan
`Chlorhexidine
`Chlorobutanol
`Chlorocresol
`Chlorodifluoroethane (HCFC)
`Chlorofluorocarbons (CFC)
`Chloroxylenol
`Cholesterol
`Citric Acid Monohydrate
`Colloidal Silicon Dioxide
`Coloring Agents
`Copovidone
`Corn Oil
`Cottonseed Oil
`Cresol
`Croscarmellose Sodium
`Crospovidone
`Cyclodextrins
`Cyclomethicone
`Denatonium Benzoate
`Dextrates
`Dextrin
`Dextrose
`Dibutyl Phthalate
`Dibutyl Sebacate
`Diethanolamine
`Diethyl Phthalate
`Difluoroethane (HFC)
`Dimethicone
`Dimethyl Ether
`Dimethyl Phthalate
`Dimethyl Sulfoxide
`Dimethylacetamide
`Disodium Edetate
`Docusate Sodium
`Edetic Acid
`Erythorbic Acid
`Erythritol
`Ethyl Acetate
`Ethyl Lactate
`Ethyl Maltol
`
`152
`155
`157
`159
`163
`168
`171
`174
`176
`180
`182
`185
`188
`192
`201
`204
`206
`208
`211
`214
`217
`222
`224
`226
`228
`231
`234
`236
`238
`240
`242
`244
`246
`248
`250
`253
`255
`257
`260
`264
`266
`268
`270
`272
`
`Ethyl Oleate
`Ethyl Vanillin
`Ethylcellulose
`Ethylene Glycol Palmitostearate
`Ethylene Vinyl Acetate
`Ethylparaben
`Fructose
`Fumaric Acid
`Gelatin
`Glucose, Liquid
`Glycerin
`Glyceryl Behenate
`Glyceryl Monooleate
`Glyceryl Monostearate
`Glyceryl Palmitostearate
`Glycofurol
`Guar Gum
`Hectorite
`Heptafluoropropane (HFC)
`Hexetidine
`Hydrocarbons (HC)
`Hydrochloric Acid
`Hydroxyethyl Cellulose
`Hydroxyethylmethyl Cellulose
`Hydroxypropyl Cellulose
`Hydroxypropyl Cellulose, Low-substituted
`Hydroxypropyl Starch
`Hypromellose
`Hypromellose Acetate Succinate
`Hypromellose Phthalate
`Imidurea
`Inulin
`Iron Oxides
`Isomalt
`Isopropyl Alcohol
`Isopropyl Myristate
`Isopropyl Palmitate
`Kaolin
`Lactic Acid
`Lactitol
`Lactose, Anhydrous
`Lactose, Monohydrate
`Lactose, Spray-Dried
`Lanolin
`
`274
`276
`278
`283
`285
`287
`290
`293
`295
`299
`301
`304
`306
`308
`311
`313
`315
`318
`321
`323
`325
`328
`330
`334
`336
`341
`344
`346
`350
`354
`359
`362
`364
`366
`371
`374
`376
`378
`381
`383
`385
`389
`396
`399
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`Lanolin Alcohols
`Lanolin, Hydrous
`Lauric Acid
`Lecithin
`Leucine
`Linoleic Acid
`Macrogol 15 Hydroxystearate
`Magnesium Aluminum Silicate
`Magnesium Carbonate
`Magnesium Oxide
`Magnesium Silicate
`Magnesium Stearate
`Magnesium Trisilicate
`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
`Monosodium Glutamate
`Monothioglycerol
`Myristic Acid
`Neohesperidin Dihydrochalcone
`Nitrogen
`Nitrous Oxide
`Octyldodecanol
`Oleic Acid
`Oleyl Alcohol
`Olive Oil
`Palmitic Acid
`Paraffin
`Peanut Oil
`Pectin
`Petrolatum
`
`Contents
`
`vii
`
`402
`404
`406
`409
`412
`414
`416
`418
`422
`426
`428
`430
`434
`436
`438
`440
`442
`445
`447
`449
`454
`457
`459
`462
`466
`471
`474
`476
`478
`480
`482
`484
`486
`488
`490
`492
`494
`496
`498
`501
`503
`505
`507
`509
`
`Petrolatum and Lanolin Alcohols
`Phenol
`Phenoxyethanol
`Phenylethyl Alcohol
`Phenylmercuric Acetate
`Phenylmercuric Borate
`Phenylmercuric Nitrate
`Phosphoric Acid
`Polacrilin Potassium
`Poloxamer
`Polycarbophil
`Polydextrose
`Polyethylene Glycol
`Polyethylene Oxide
`Polymethacrylates
`Poly(methyl vinyl ether/maleic anhydride)
`Polyoxyethylene Alkyl Ethers
`Polyoxyethylene Castor Oil Derivatives
`Polyoxyethylene Sorbitan Fatty Acid Esters
`Polyoxyethylene Stearates
`Polyvinyl Acetate Phthalate
`Polyvinyl Alcohol
`Potassium Alginate
`Potassium Benzoate
`Potassium Bicarbonate
`Potassium Chloride
`Potassium Citrate
`Potassium Hydroxide
`Potassium Metabisulfite
`Potassium Sorbate
`Povidone
`Propionic Acid
`Propyl Gallate
`Propylene Carbonate
`Propylene Glycol
`Propylene Glycol Alginate
`Propylparaben
`2-Pyrrolidone
`Raffinose
`Saccharin
`Saccharin Sodium
`Saponite
`Sesame Oil
`Shellac
`
`512
`514
`517
`519
`521
`524
`526
`530
`532
`535
`539
`542
`545
`551
`553
`561
`564
`572
`580
`585
`589
`592
`594
`596
`598
`600
`603
`605
`607
`609
`611
`617
`619
`622
`624
`627
`629
`633
`635
`638
`641
`644
`646
`649
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`Thymol
`Titanium Dioxide
`Tragacanth
`Trehalose
`Triacetin
`Tributyl Citrate
`Triethanolamine
`Triethyl Citrate
`Vanillin
`Vegetable Oil, Hydrogenated
`Water
`Wax, Anionic Emulsifying
`Wax, Carnauba
`Wax, Cetyl Esters
`Wax, Microcrystalline
`Wax, Nonionic Emulsifying
`Wax, White
`Wax, Yellow
`Xanthan Gum
`Xylitol
`Zein
`Zinc Acetate
`Zinc Stearate
`
`780
`782
`785
`788
`790
`792
`794
`796
`798
`800
`802
`807
`809
`811
`813
`815
`817
`819
`821
`824
`828
`830
`832
`
`Appendix I: Suppliers’ Directory 835
`Appendix II: List of Excipient ‘E’ Numbers 882
`Appendix III: List of Excipient ‘EINECS’ Numbers 884
`Appendix IV: List of Excipient Molecular Weights 886
`Index 889
`
`viii
`
`Contents
`
`Simethicone
`Sodium Acetate
`Sodium Alginate
`Sodium Ascorbate
`Sodium Benzoate
`Sodium Bicarbonate
`Sodium Borate
`Sodium Chloride
`Sodium Citrate Dihydrate
`Sodium Cyclamate
`Sodium Hyaluronate
`Sodium Hydroxide
`Sodium Lactate
`Sodium Lauryl Sulfate
`Sodium Metabisulfite
`Sodium Phosphate, Dibasic
`Sodium Phosphate, Monobasic
`Sodium Propionate
`Sodium Starch Glycolate
`Sodium Stearyl Fumarate
`Sodium Sulfite
`Sorbic Acid
`Sorbitan Esters (Sorbitan Fatty Acid Esters)
`Sorbitol
`Soybean Oil
`Starch
`Starch, Pregelatinized
`Starch, Sterilizable Maize
`Stearic Acid
`Stearyl Alcohol
`Sucralose
`Sucrose
`Sugar, Compressible
`Sugar, Confectioner’s
`Sugar Spheres
`Sulfobutylether b-Cyclodextrin
`Sulfuric Acid
`Sunflower Oil
`Suppository Bases, Hard Fat
`Talc
`Tartaric Acid
`Tetrafluoroethane (HFC)
`Thaumatin
`Thimerosal
`
`652
`654
`656
`659
`662
`665
`669
`671
`675
`678
`681
`683
`685
`687
`690
`693
`696
`699
`701
`705
`708
`710
`713
`718
`722
`725
`731
`734
`737
`740
`742
`744
`748
`750
`752
`754
`758
`760
`762
`767
`770
`772
`775
`777
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`Alcohol
`
`1 Nonproprietary Names
`BP: Ethanol (96%)
`JP: Ethanol
`PhEur: Ethanolum (96 per centum)
`USP: Alcohol
`
`2 Synonyms
`Ethyl alcohol; ethyl hydroxide; grain alcohol; methyl carbinol.
`
`3 Chemical Name and CAS Registry Number
`Ethanol [64-17-5]
`
`4 Empirical Formula and Molecular Weight
`46.07
`C2H6O
`
`5 Structural Formula
`
`6 Functional Category
`Antimicrobial preservative; disinfectant; skin penetrant; sol-
`vent.
`
`7 Applications in Pharmaceutical Formulation
`or Technology
`Ethanol and aqueous ethanol solutions of various concentra-
`tions (see Sections 8 and 17) are widely used in pharmaceutical
`formulations and cosmetics; see Table I. Although ethanol is
`primarily used as a solvent, it is also employed in solutions as an
`antimicrobial preservative.(1,2) Topical ethanol solutions are
`also used as penetration enhancers(3–6) and as disinfectants.
`Ethanol has also been used in transdermal preparations in
`combination with Labrasol as a co-surfactant.(7)
`
`Table I:
`
`Uses of alcohol.
`
`Use
`
`Concentration (% v/v)
`
`Antimicrobial preservative
`Disinfectant
`Extracting solvent in galenical manufacture
`Solvent in film coating
`Solvent in injectable solutions
`Solvent in oral liquids
`Solvent in topical products
`
`510
`60–90
`Up to 85
`Variable
`Variable
`Variable
`60–90
`
`8 Description
`the term ‘ethanol’ used without other
`In the BP 2004,
`qualification refers to ethanol containing 599.5% v/v of
`C2H6O. The term ‘alcohol’, without other qualification, refers
`
`to ethanol 95.1–96.9% v/v. Where other strengths are intended,
`the term ‘alcohol’ or ‘ethanol’
`is used,
`followed by the
`statement of the strength.
`In the PhEur 2005, anhydrous ethanol contains not less than
`99.5% v/v of C2H6O at 208C. The term ethanol (96%) is used
`to describe the material containing water and 95.1–96.9% v/v
`of C2H6O at 208C.
`In the USP 28, the term ‘dehydrated alcohol’ refers to
`ethanol 599.5% v/v. The term ‘alcohol’ without other
`qualification refers to ethanol 94.9–96.0% v/v.
`In the JP 2001, ethanol (alcohol) contains 95.1–95.6% v/v
`(by specific gravity) of C2H6O at 158C.
`In the Handbook of Pharmaceutical Excipients, the term
`‘alcohol’ is used for either ethanol 95% v/v or ethanol 96% v/v.
`Alcohol is a clear, colorless, mobile, and volatile liquid with
`a slight, characteristic odor and burning taste.
`See also Section 17.
`
`9 Pharmacopeial Specifications
`See Table II.
`
`10 Typical Properties
`Antimicrobial activity: ethanol
`in aqueous
`is bactericidal
`mixtures at concentrations between 60% and 95% v/v;
`the optimum concentration is generally considered to be
`70% v/v. Antimicrobial activity is enhanced in the presence
`of edetic acid or edetate salts.(1) Ethanol is inactivated in the
`presence of nonionic surfactants and is ineffective against
`bacterial spores.
`Boiling point: 78.158C
`Flammability: readily flammable, burning with a blue, smoke-
`less flame.
`Flash point: 148C (closed cup)
`Solubility: miscible with chloroform, ether, glycerin, and water
`(with rise of temperature and contraction of volume).
`Specific gravity: 0.8119–0.8139 at 208C
`Note: the above typical properties are for alcohol (ethanol 95%
`or 96% v/v). See Section 17 for typical properties of
`dehydrated alcohol.
`
`11 Stability and Storage Conditions
`Aqueous ethanol solutions may be sterilized by autoclaving or
`by filtration and should be stored in airtight containers, in a
`cool place.
`
`12 Incompatibilities
`In acidic conditions, ethanol solutions may react vigorously
`with oxidizing materials. Mixtures with alkali may darken in
`color owing to a reaction with residual amounts of aldehyde.
`Organic salts or acacia may be precipitated from aqueous
`solutions or dispersions. Ethanol solutions are also incompa-
`tible with aluminum containers and may interact with some
`drugs.
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`Table II:
`
`Pharmacopeial specifications for alcohol.
`
`Test
`
`4 200 ppm
`4 2 ppm
`4 10 ppm
`
`—
`
`—
`
`—
`þ
`
`—
`—
`—
`þ
`
`—
`þ
`41.2 ppm
`95.1–95.6%
`
`USP 28
`PhEur 2005
`JP 2001
`þ
`þ
`þ
`Identification
`þ
`þ
`—
`Characters
`0.814–0.816 0.805–0.812 0.812–0.816
`Specific gravity
`Acidity or alkalinity þ
`þ
`þ
`þ
`þ
`Clarity of solution
`—
`Nonvolatile residue 41 mg/40 mL 425 ppm
`41 mg/40 mL
`þ
`Water-insoluble
`—
`—
`substances
`þ
`þ
`Volatile impurities
`—
`þ
`410 ppm v/v þ
`Aldehydes
`þ
`Amyl alcohol, etc. —
`—
`þ
`Absorbance
`—
`—
`4 0.40
`at 240 nm
`—
`—
`4 0.30
`at 250–260 nm —
`—
`4 0.10
`at 270–340 nm —
`—
`Fusel oil constituents þ
`—
`—
`þ
`Acetone and
`—
`—
`propan-2-ol
`þ
`Methanol
`Benzene
`—
`Acetaldehyde and
`—
`acetal
`Reducing
`substances
`Organic volatile
`impurities
`Chloride
`Heavy metals
`Assay
`
`—
`—
`—
`—
`95.1–96.9% 92.3–93.8%
`by weight
`94.9–96.0%
`by volume
`
`13 Method of Manufacture
`Ethanol is manufactured by the controlled enzymatic fermenta-
`tion of starch, sugar, or other carbohydrates. A fermented
`liquid is produced containing about 15% ethanol; ethanol 95%
`v/v is then obtained by fractional distillation. Ethanol may also
`be prepared by a number of synthetic methods.
`
`14 Safety
`Ethanol and aqueous ethanol solutions are widely used in a
`variety of pharmaceutical formulations and cosmetics. It is also
`consumed in alcoholic beverages.
`Ethanol is rapidly absorbed from the gastrointestinal tract
`and the vapor may be absorbed through the lungs;
`it is
`metabolized, mainly in the liver, to acetaldehyde, which is
`further oxidized to acetate.
`Ethanol is a central nervous system depressant and ingestion
`of low to moderate quantities can lead to symptoms of
`intoxication including muscle incoordination, visual impair-
`ment, slurred speech, etc. Ingestion of higher concentrations
`may cause depression of medullary action, lethargy, amnesia,
`hypothermia, hypoglycemia, stupor, coma, respiratory depres-
`sion, and cardiovascular collapse. The lethal human blood-
`alcohol concentration is generally estimated to be 400–500 mg/
`100 mL.
`intoxication are usually
`Although symptoms of ethanol
`encountered following deliberate consumption of ethanol-
`
`Alcohol
`
`19
`
`containing beverages, many pharmaceutical products contain
`ethanol as a solvent, which, if ingested in sufficiently large
`quantities, may cause adverse symptoms of intoxication. In the
`USA, the maximum quantity of alcohol
`included in OTC
`medicines is 10% v/v for products labeled for use by people of
`12 years of age and older, 5% v/v for products intended for use
`by children aged 6–12 years of age, and 0.5% v/v for products
`for use by children under 6 years of age.(8)
`Parenteral products containing up to 50% of alcohol
`(ethanol 95 or 96% v/v) have been formulated. However,
`such concentrations can produce pain on intramuscular
`injection and lower concentrations such as 5–10% v/v are
`preferred. Subcutaneous injection of alcohol (ethanol 95% v/v)
`similarly causes considerable pain followed by anesthesia. If
`injections are made close to nerves, neuritis and nerve
`degeneration may occur. This effect is used therapeutically to
`cause anesthesia in cases of severe pain, although the practice of
`using alcohol in nerve blocks is controversial. Doses of 1 mL of
`absolute alcohol have been used for this purpose.(9)
`Preparations containing more than 50% v/v alcohol may
`cause skin irritation when applied topically.
`LD50 (mouse, IP): 0.93 g/kg(10)
`LD50 (mouse, IV): 1.97 g/kg
`LD50 (mouse, oral): 3.45 g/kg
`LD50 (mouse, SC): 8.29 g/kg
`LD50 (rat, IP): 3.75 g/kg
`LD50 (rat, IV): 1.44 g/kg
`LD50 (rat, oral): 7.06 g/kg
`
`15 Handling Precautions
`Observe normal precautions appropriate to the circumstances
`and quantity of material handled. Ethanol and aqueous ethanol
`solutions should be handled in a well-ventilated environment.
`In the UK, the long-term 8-hour TWA exposure limit for
`ethanol is 1920 mg/m3 (1000 ppm).(11) Ethanol may be irritant
`to the eyes and mucous membranes and eye protection and
`gloves are recommended. Ethanol is flammable and should be
`heated with care. Fixed storage tanks should be electrically
`grounded to avoid ignition from electrostatic discharges when
`ethanol is transferred.
`
`16 Regulatory Status
`Included in the FDA Inactive Ingredients Guide (dental
`preparations;
`inhalations; IM, IV, and SC injections; nasal
`and ophthalmic preparations; oral capsules, solutions, suspen-
`sions, syrups, and tablets; rectal, topical, and transdermal
`preparations). Included in the Canadian List of Acceptable
`Non-medicinal
`Ingredients. Included in nonparenteral and
`parenteral medicines licensed in the UK.
`
`17 Related Substances
`Dehydrated alcohol; denatured alcohol; dilute alcohol; iso-
`propyl alcohol.
`
`Dehydrated alcohol
`Synonyms: absolute alcohol; anhydrous ethanol; ethanol.
`Autoignition temperature: 3658C
`Boiling point: 78.58C
`Explosive limits: 3.5–19.0% v/v in air
`Flash point: 128C (closed cup)
`Melting point: 1128C
`Moisture content: absorbs water rapidly from the air.
`
`Neurelis - EX.2029
`Aquestive Therapeutics, Inc. v. Neurelis, Inc. - IPR2019-00451
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`

`20
`
`Alcohol
`
`20 = 1.361
`Refractive index: nD
`Specific gravity: 0.7904–0.7935 at 208C
`Surface tension: 22.75 mN/m at 208C (ethanol/vapor)
`Vapor density (relative): 1.59 (air = 1)
`Vapor pressure: 5.8 Pa at 208C
`Viscosity (dynamic): 1.22 mPa s (1.22 cP) at 208C
`Comments: dehydrated alcohol is ethanol 599.5% v/v. See
`Section 8.
`
`Denatured alcohol
`Synonyms: industrial methylated spirit; surgical spirit.
`Comments: denatured alcohol is alcohol intended for external
`use only. It has been rendered unfit for human consumption
`by the addition of a denaturing agent such as methanol or
`methyl isobutyl ketone.
`
`Dilute alcohol
`Synonyms: dilute ethanol.
`Specific gravity: see Table III.
`
`Table III:
`
`Specific gravity of alcohol.
`
`Strength of alcohol (% v/v)
`
`Specific gravity at 208C
`
`90
`80
`70
`60
`50
`45
`25
`20
`
`0.8289–0.8319
`0.8599–0.8621
`0.8860–0.8883
`0.9103–0.9114
`0.9314–0.9326
`0.9407–0.9417
`0.9694–0.9703
`0.9748–0.9759
`
`Comments: the term ‘dilute alcohol’ refers to a mixture of
`ethanol and water of stated concentration. The BP 2004 lists
`eight strengths of dilute alcohol (dilute ethanol) containing
`90%, 80%, 70%, 60%, 50%, 45%, 25%, and 20% v/v
`respectively of ethanol.
`
`18 Comments
`Possession and use of nondenatured alcohols are usually
`subject to close control by excise authorities.
`A specification for alcohol
`is contained in the Food
`Chemicals Codex (FCC).
`The EINECS number for alcohol is 200-578-6.
`
`19 Specific References
`1 Chiori CO, Ghobashy AA. A potentiating effect of EDTA on the
`bactericidal activity of lower concentrations of ethanol. Int J
`Pharm 1983; 17: 121–128.
`2 Karabit MS, Juneskans OT, Lundgren P. Studies on the evaluation
`of preservative efficacy. IV. The determination of antimicrobial
`characteristics of some pharmaceutical compounds in aqueous
`solutions. Int J Pharm 1989; 54: 51–56.
`3 Liu P, Higuchi WI, Song W, et al. Quantitative evaluation of
`ethanol effects on diffusion and metabolism of b-estradiol
`in
`hairless mouse skin. Pharm Res 1991; 8(7): 865–872.
`4 Verma DD, Fahr A. Synergistic penetration enhancement of
`ethanol and phospholipids on the topical delivery of cyclosporin
`A. J Controlled Release 2004; 97(1): 55–66.
`5 Gwak SS, Oh IS, Chun IK. Transdermal delivery of ondansetron
`hydrochloride: effects of vehicles and penetration enhancers. Drug
`Dev Ind Pharm 2004; 30(2): 187–194.
`6 Williams AC, Barry BW. Penetration enhancers. Adv Drug
`Delivery Rev 2004; 56(5): 603–618.
`7 Kwean JH, Chi SC, Park ES. Transdermal delivery of diclofenac
`using microemulsions. Arch Pharmacol Res 2004; 27(3): 351–356.
`8 Jass HE. Regulatory review. Cosmet Toilet 1995; 110(5): 21–22.
`9 Lloyd JW. Use of anaesthesia: the anaesthetist and the pain clinic.
`Br Med J 1980; 281: 432–434.
`10 Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials,
`11th edn. New York: Wiley, 2004: 1627–1628.
`11 Health and Safety Executive. EH40/2002: Occupational Exposure
`Limits 2002. Sudbury: Health and Safety Executive, 2002.
`
`20 General References
`Lund W, ed. The Pharmaceutical Codex: Principles and Practice of
`Pharmaceutics, 12th edn. London: Pharmaceutical Press, 1994:
`694–695.
`Spiegel AJ, Noseworthy MN. Use of nonaqueous solvents in parenteral
`products. J Pharm Sci 1963; 52: 917–927.
`Wade A, ed. Pharmaceutical Handbook, 19th edn. London: Pharma-
`ceutical Press, 1980: 227–230.
`
`21 Authors
`SC Owen.
`
`22 Date of Revision
`10 February 2005.
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`Neurelis - EX.2029
`Aquestive Therapeutics, Inc. v. Neurelis, Inc. - IPR2019-00451
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