h"
`
`'1
`
`Handbook of
`(cid:61)(cid:86)(cid:99)(cid:89)(cid:87)(cid:100)(cid:100)(cid:96)(cid:21)(cid:100)(cid:91)(cid:21)
`Pharmaceutical EXCipients
`(cid:69)(cid:93)(cid:86)(cid:103)(cid:98)(cid:86)(cid:88)(cid:90)(cid:106)(cid:105)(cid:94)(cid:88)(cid:86)(cid:97)(cid:21)(cid:58)(cid:109)(cid:88)(cid:94)(cid:101)(cid:94)(cid:90)(cid:99)(cid:105)(cid:104)
`(cid:72)(cid:94)(cid:109)(cid:105)(cid:93)(cid:21)(cid:90)(cid:89)(cid:94)(cid:105)(cid:94)(cid:100)(cid:99)
`Sixth edition
`
`(cid:58)(cid:89)(cid:94)(cid:105)(cid:90)(cid:89)(cid:21)(cid:87)(cid:110)(cid:21)
`Edited by
`(cid:71)(cid:86)(cid:110)(cid:98)(cid:100)(cid:99)(cid:89)(cid:21)(cid:56)(cid:21)(cid:71)(cid:100)(cid:108)(cid:90)(cid:33)(cid:21)(cid:69)(cid:86)(cid:106)(cid:97)(cid:21)(cid:63)(cid:21)(cid:72)(cid:93)(cid:90)(cid:104)(cid:96)(cid:90)(cid:110)(cid:21)(cid:86)(cid:99)(cid:89)(cid:21)(cid:66)(cid:86)(cid:103)(cid:94)(cid:86)(cid:99)(cid:21)(cid:58)(cid:21)(cid:70)(cid:106)(cid:94)(cid:99)(cid:99)
`
`v on, C Rowe, Paul J Sheskeyand Marian E Quinn
`
`MYLAN EXHIBIT 1033
`
`

`

`Handbook of Pharmaceutical Excipients
`
`

`

`Handbook of
`Pharmaceutical Excipients
`
`S I X T H E D I T I O N
`
`Edited by
`Raymond C Rowe BPharm, PhD, DSC, FRPharmS, FRSC, CPhys, MInstP
`Chief Scientist
`Intelligensys Ltd, Stokesley, North Yorkshire, UK
`Paul J Sheskey BSc, RPh
`Application Development Leader
`The Dow Chemical Company, Midland, MI, USA
`Marian E Quinn BSc, MSc
`Development Editor
`Royal Pharmaceutical Society of Great Britain, London, UK
`
`London . Chicago
`
`

`

`Published by the Pharmaceutical Press
`An imprint of RPS Publishing
`
`1 Lambeth High Street, London SE1 7JN, UK
`100 South Atkinson Road, Suite 200, 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 2009
`
`is a trade mark of RPS Publishing
`
`RPS Publishing is the publishing organisation of the Royal Pharmaceutical Society of Great Britain
`
`First published 1986
`Second edition published 1994
`Third edition published 2000
`Fourth edition published 2003
`Fifth edition published 2006
`Sixth edition published 2009
`
`Typeset by Data Standards Ltd, Frome, Somerset
`Printed 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 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
`
`

`

`56
`59
`61
`64
`66
`68
`70
`73
`75
`77
`78
`
`82
`83
`86
`89
`91
`92
`94
`96
`99
`101
`103
`105
`108
`110
`115
`117
`118
`122
`126
`128
`129
`
`134
`136
`139
`141
`143
`146
`148
`
`Benzalkonium Chloride
`Benzethonium Chloride
`Benzoic Acid
`Benzyl Alcohol
`Benzyl Benzoate
`Boric Acid
`Bronopol
`Butylated Hydroxyanisole
`Butylated Hydroxytoluene
`Butylene Glycol
`Butylparaben
`
`C C
`
`alcium Acetate
`Calcium Alginate
`Calcium Carbonate
`Calcium Chloride
`Calcium Hydroxide
`Calcium Lactate
`Calcium Phosphate, Dibasic Anhydrous
`Calcium Phosphate, Dibasic Dihydrate
`Calcium Phosphate, Tribasic
`Calcium Silicate
`Calcium Stearate
`Calcium Sulfate
`Canola Oil
`Carbomer
`Carbon Dioxide
`Carboxymethylcellulose Calcium
`Carboxymethylcellulose Sodium
`Carrageenan
`Castor Oil
`Castor Oil, Hydrogenated
`Cellulose, Microcrystalline
`Cellulose, Microcrystalline and
`Carboxymethylcellulose Sodium
`Cellulose, Powdered
`Cellulose, Silicified Microcrystalline
`Cellulose Acetate
`Cellulose Acetate Phthalate
`Ceratonia
`Ceresin
`
`1
`3
`5
`7
`8
`10
`11
`13
`14
`17
`20
`23
`28
`29
`31
`34
`35
`37
`38
`39
`41
`42
`43
`46
`48
`51
`
`53
`
`Contents
`
`Preface x
`xi
`Arrangement
`xiii
`Acknowledgments
`xiii
`Notice to Readers
`International Steering Committee xiv
`Editorial Staff
`xv
`Contributors
`xvi
`About the Editors
`New Monographs
`Related Substances
`Bibliography
`xxiv
`Abbreviations
`xxv
`Units of Measurement
`
`xx
`xxi
`xxii
`
`xxvii
`
`Monographs
`
`A A
`
`cacia
`Acesulfame Potassium
`Acetic Acid, Glacial
`Acetone
`Acetyltributyl Citrate
`Acetyltriethyl Citrate
`Adipic Acid
`Agar
`Albumin
`Alcohol
`Alginic Acid
`Aliphatic Polyesters
`Alitame
`Almond Oil
`Alpha Tocopherol
`Aluminum Hydroxide Adjuvant
`Aluminum Monostearate
`Aluminum Oxide
`Aluminum Phosphate Adjuvant
`Ammonia Solution
`Ammonium Alginate
`Ammonium Chloride
`Ascorbic Acid
`Ascorbyl Palmitate
`Aspartame
`Attapulgite
`
`B B
`
`entonite
`
`

`

`251
`253
`256
`257
`259
`261
`262
`267
`268
`270
`
`273
`276
`
`278
`282
`283
`286
`288
`290
`293
`295
`297
`298
`
`301
`303
`304
`306
`308
`309
`311
`314
`315
`317
`322
`325
`326
`330
`333
`
`337
`339
`
`Erythritol
`Ethyl Acetate
`Ethyl Lactate
`Ethyl Maltol
`Ethyl Oleate
`Ethyl Vanillin
`Ethylcellulose
`Ethylene Glycol Stearates
`Ethylene Vinyl Acetate
`Ethylparaben
`
`F F
`
`ructose
`Fumaric Acid
`
`G G
`
`elatin
`Glucose, Liquid
`Glycerin
`Glyceryl Behenate
`Glyceryl Monooleate
`Glyceryl Monostearate
`Glyceryl Palmitostearate
`Glycine
`Glycofurol
`Guar Gum
`
`H H
`
`ectorite
`Heptafluoropropane (HFC)
`Hexetidine
`Hydrocarbons (HC)
`Hydrochloric Acid
`Hydrophobic Colloidal Silica
`Hydroxyethyl Cellulose
`Hydroxyethylmethyl Cellulose
`Hydroxypropyl Betadex
`Hydroxypropyl Cellulose
`Hydroxypropyl Cellulose, Low-substituted
`Hydroxypropyl Starch
`Hypromellose
`Hypromellose Acetate Succinate
`Hypromellose Phthalate
`
`I I
`
`midurea
`Inulin
`
`150
`152
`155
`157
`159
`162
`166
`168
`171
`173
`176
`178
`181
`184
`185
`189
`196
`199
`200
`202
`203
`206
`208
`210
`215
`
`217
`218
`220
`222
`225
`227
`228
`230
`232
`233
`235
`236
`238
`241
`242
`244
`
`247
`250
`
`vi
`
`Contents
`
`Cetostearyl Alcohol
`Cetrimide
`Cetyl Alcohol
`Cetylpyridinium Chloride
`Chitosan
`Chlorhexidine
`Chlorobutanol
`Chlorocresol
`Chlorodifluoroethane (HCFC)
`Chlorofluorocarbons (CFC)
`Chloroxylenol
`Cholesterol
`Citric Acid Monohydrate
`Coconut Oil
`Colloidal Silicon Dioxide
`Coloring Agents
`Copovidone
`Corn Oil
`Corn Starch and Pregelatinized Starch
`Cottonseed Oil
`Cresol
`Croscarmellose Sodium
`Crospovidone
`Cyclodextrins
`Cyclomethicone
`
`D D
`
`enatonium 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
`
`E E
`
`detic Acid
`Erythorbic Acid
`
`

`

`Contents
`
`vii
`
`436
`438
`441
`445
`447
`449
`450
`452
`454
`455
`456
`
`458
`460
`461
`463
`
`465
`466
`468
`470
`
`473
`474
`476
`478
`480
`481
`484
`485
`488
`490
`492
`494
`496
`499
`503
`504
`506
`509
`513
`515
`517
`522
`
`Methionine
`Methylcellulose
`Methylparaben
`Mineral Oil
`Mineral Oil, Light
`Mineral Oil and Lanolin Alcohols
`Monoethanolamine
`Monosodium Glutamate
`Monothioglycerol
`Myristic Acid
`Myristyl Alcohol
`
`N N
`
`eohesperidin Dihydrochalcone
`Neotame
`Nitrogen
`Nitrous Oxide
`
`O O
`
`ctyldodecanol
`Oleic Acid
`Oleyl Alcohol
`Olive Oil
`
`P P
`
`almitic Acid
`Paraffin
`Peanut Oil
`Pectin
`Pentetic Acid
`Petrolatum
`Petrolatum and Lanolin Alcohols
`Phenol
`Phenoxyethanol
`Phenylethyl Alcohol
`Phenylmercuric Acetate
`Phenylmercuric Borate
`Phenylmercuric Nitrate
`Phospholipids
`Phosphoric Acid
`Polacrilin Potassium
`Poloxamer
`Polycarbophil
`Polydextrose
`Poly (DL-Lactic Acid)
`Polyethylene Glycol
`Polyethylene Oxide
`
`340
`342
`346
`348
`350
`
`352
`
`Iron Oxides
`Isomalt
`Isopropyl Alcohol
`Isopropyl Myristate
`Isopropyl Palmitate
`
`K K
`
`aolin
`
`L L
`
`355
`actic Acid
`357
`Lactitol
`359
`Lactose, Anhydrous
`362
`Lactose, Inhalation
`364
`Lactose, Monohydrate
`370
`Lactose, Monohydrate and Corn Starch
`Lactose, Monohydrate and Microcrystalline Cellulose 371
`Lactose, Monohydrate and Povidone
`373
`Lactose, Monohydrate and Powdered Cellulose
`374
`Lactose, Spray-Dried
`376
`Lanolin
`378
`Lanolin, Hydrous
`380
`Lanolin Alcohols
`382
`Lauric Acid
`383
`Lecithin
`385
`Leucine
`387
`Linoleic Acid
`389
`
`391
`393
`397
`400
`402
`404
`408
`410
`411
`414
`416
`418
`421
`422
`424
`429
`431
`433
`
`M M
`
`acrogol 15 Hydroxystearate
`Magnesium Aluminum Silicate
`Magnesium Carbonate
`Magnesium Oxide
`Magnesium Silicate
`Magnesium Stearate
`Magnesium Trisilicate
`Maleic Acid
`Malic Acid
`Maltitol
`Maltitol Solution
`Maltodextrin
`Maltol
`Maltose
`Mannitol
`Medium-chain Triglycerides
`Meglumine
`Menthol
`
`

`

`640
`643
`645
`646
`648
`650
`651
`654
`656
`659
`661
`663
`667
`669
`671
`672
`675
`679
`682
`685
`691
`695
`697
`700
`701
`703
`707
`709
`710
`712
`714
`718
`719
`721
`722
`
`727
`728
`731
`733
`735
`736
`739
`741
`744
`
`Sodium Citrate Dihydrate
`Sodium Cyclamate
`Sodium Formaldehyde Sulfoxylate
`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
`Sodium Thiosulfate
`Sorbic Acid
`Sorbitan Esters (Sorbitan Fatty Acid Esters)
`Sorbitol
`Soybean Oil
`Starch
`Starch, Pregelatinized
`Starch, Sterilizable Maize
`Stearic Acid
`Stearyl Alcohol
`Sucralose
`Sucrose
`Sucrose Octaacetate
`Sugar, Compressible
`Sugar, Confectioner’s
`Sugar Spheres
`Sulfobutylether b-Cyclodextrin
`Sulfur Dioxide
`Sulfuric Acid
`Sunflower Oil
`Suppository Bases, Hard Fat
`
`T T
`
`agatose
`Talc
`Tartaric Acid
`Tetrafluoroethane (HFC)
`Thaumatin
`Thimerosal
`Thymol
`Titanium Dioxide
`Tragacanth
`
`525
`534
`536
`542
`549
`554
`557
`562
`564
`566
`567
`569
`570
`572
`574
`576
`577
`579
`581
`586
`587
`590
`592
`594
`596
`599
`600
`
`603
`
`605
`608
`610
`612
`614
`616
`619
`620
`622
`625
`627
`629
`633
`635
`637
`
`viii
`
`Contents
`
`Polymethacrylates
`Poly(methyl vinyl ether/maleic anhydride)
`Polyoxyethylene Alkyl Ethers
`Polyoxyethylene Castor Oil Derivatives
`Polyoxyethylene Sorbitan Fatty Acid Esters
`Polyoxyethylene Stearates
`Polyoxylglycerides
`Polyvinyl Acetate Phthalate
`Polyvinyl Alcohol
`Potassium Alginate
`Potassium Alum
`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
`Propylparaben Sodium
`Pyrrolidone
`
`R R
`
`affinose
`
`S S
`
`accharin
`Saccharin Sodium
`Safflower Oil
`Saponite
`Sesame Oil
`Shellac
`Simethicone
`Sodium Acetate
`Sodium Alginate
`Sodium Ascorbate
`Sodium Benzoate
`Sodium Bicarbonate
`Sodium Borate
`Sodium Carbonate
`Sodium Chloride
`
`

`

`Contents
`
`ix
`
`779
`780
`
`782
`786
`
`790
`791
`793
`
`795
`847
`849
`852
`855
`
`Wax, White
`Wax, Yellow
`
`X X
`
`anthan Gum
`Xylitol
`
`Z Z
`
`ein
`Zinc Acetate
`Zinc Stearate
`
`Appendix I: Suppliers Directory
`Appendix II: List of Excipient ‘E’ Numbers
`Appendix III: List of Excipient ‘EINECS’ Numbers
`Appendix IV: List of Excipient Molecular Weights
`Index
`
`746
`748
`749
`751
`754
`756
`757
`
`760
`762
`764
`
`766
`770
`772
`774
`775
`777
`
`Trehalose
`Triacetin
`Tributyl Citrate
`Tricaprylin
`Triethanolamine
`Triethyl Citrate
`Triolein
`
`V V
`
`anillin
`Vegetable Oil, Hydrogenated
`Vitamin E Polyethylene Glycol Succinate
`
`W W
`
`ater
`Wax, Anionic Emulsifying
`Wax, Carnauba
`Wax, Cetyl Esters
`Wax, Microcrystalline
`Wax, Nonionic Emulsifying
`
`

`

`Sodium Lauryl Sulfate
`
`651
`
`2 Middleton JD. Sodium lactate as a moisturizer. Cosmet Toiletries 1978;
`93(3): 85–86.
`3 Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th
`edn. New York: Wiley, 2004; 2197–2198.
`
`20 General References
`
`— 2
`
`1 Author
`HJ de Jong.
`
`medicines licensed in the UK. Included in the Canadian List of
`Acceptable Non-medicinal Ingredients.
`
`17 Related Substances
`Lactic Acid.
`
`18 Comments
`Generally, the commercially available product is a mixture with
`water containing 70–80% sodium lactate.
`The EINECS number for sodium lactate is 200-772-0. The
`PubChem Compound ID (CID) for sodium lactate is 23666456.
`
`19 Specific References
`1 Suomela A, Kristoffersson E. Dry skin and moisturizing agents. Acta
`Pharm Fenn 1983; 92(2): 67–76.
`
`22 Date of Revision
`13 January 2009.
`
`Sodium Lauryl Sulfate
`
`Nonproprietary Names
`1
`BP: Sodium Lauryl Sulphate
`JP: Sodium Lauryl Sulfate
`PhEur: Sodium Laurilsulfate
`USP-NF: Sodium Lauryl Sulfate
`
`Synonyms
`2
`Dodecyl alcohol hydrogen sulfate, sodium salt; dodecyl sodium
`sulfate; dodecylsulfate sodium salt; Elfan 240;
`lauryl sodium
`sulfate; lauryl sulfate, sodium salt; monododecyl sodium sulfate;
`natrii
`laurilsulfas; sodium dodecyl sulfate; sodium n-dodecyl
`sulfate; sodium laurilsulfate; sodium monododecyl sulfate; sodium
`monolauryl sulfate; SDS; SLS; sulfuric acid monododecyl ester,
`sodium salt; Texapon K12P.
`
`Functional Category
`6
`Anionic surfactant; detergent; emulsifying agent; skin penetrant;
`tablet and capsule lubricant; wetting agent.
`
`7
`
`Applications in Pharmaceutical Formulation or
`Technology
`Sodium lauryl sulfate is an anionic surfactant employed in a wide
`range of nonparenteral pharmaceutical formulations and cosmetics;
`see Table I.
`It is a detergent and wetting agent effective in both alkaline and
`acidic conditions. In recent years it has found application in
`analytical electrophoretic techniques: SDS (sodium dodecyl sulfate)
`polyacrylamide gel electrophoresis is one of the more widely used
`techniques for the analysis of proteins;(1) and sodium lauryl sulfate
`has been used to enhance the selectivity of micellar electrokinetic
`chromatography (MEKC).(2)
`
`S
`
`Chemical Name and CAS Registry Number
`3
`Sulfuric acid monododecyl ester sodium salt (1 : 1) [151-21-3]
`
`Table I: Uses of sodium lauryl sulfate.
`
`Use
`
`Concentration (%)
`
`Empirical Formula and Molecular Weight
`4
`C12H25NaO4S
`288.38
`The USP32–NF27 describes sodium lauryl sulfate as a mixture of
`sodium alkyl sulfates consisting chiefly of sodium lauryl sulfate
`[CH3(CH2)10CH2OSO3Na]. The PhEur 6.0 states that sodium
`lauryl sulfate should contain not less than 85% of sodium alkyl
`sulfates calculated as C12H25NaO4S.
`
`5
`
`Structural Formula
`
`Anionic emulsifier, forms self-emulsifying bases with
`fatty alcohols
`Detergent in medicated shampoos
`Skin cleanser in topical applications
`Solubilizer in concentrations greater than critical
`micelle concentration
`Tablet lubricant
`Wetting agent in dentrifices
`
`0.5–2.5
`10
`1
`>0.0025
`
`1.0–2.0
`1.0–2.0
`
`Description
`8
`Sodium lauryl sulfate consists of white or cream to pale yellow-
`colored crystals, flakes, or powder having a smooth feel, a soapy,
`bitter taste, and a faint odor of fatty substances.
`
`Pharmacopeial Specifications
`9
`See Table II. See also Section 18.
`
`

`

`2325
`
`0.4
`
`2295
`
`1747
`
`1678
`
`log(1/R)
`
`2350
`
`2311
`
`1215
`
`1764
`
`1950
`
`2269
`
`1730
`
`2.0
`
`0.0
`
`−4.0
`−0.2
`1100 1300 1500 1700 1900 2100 2300 2500
`Wavelength/nm
`
`1000 × [2nd deriv. log(1/R)
`
`Figure 1: Near-infrared spectrum of sodium lauryl sulfate measured by
`reflectance.
`
`Acid value 0
`Antimicrobial activity Sodium lauryl sulfate has some bacterio-
`static action against Gram-positive bacteria but is ineffective
`against many Gram-negative microorganisms. It potentiates the
`fungicidal activity of certain substances such as sulfanilamide
`and sulfathiazole.
`Critical micelle concentration 8.2 mmol/L (2.365 g/L) at 208C
`Density 1.07 g/cm3 at 208C
`HLB value 40
`Interfacial tension 11.8 mN/m (11.8 dynes/cm) for a 0.05% w/v
`solution (unspecified nonaqueous liquid) at 308C.
`Melting point 204–2078C (for pure substance)
`Moisture content 45%; sodium lauryl sulfate is not hygroscopic.
`NIR spectra see Figure 1.
`Solubility Freely soluble in water, giving an opalescent solution;
`practically insoluble in chloroform and ether.
`Spreading coefficient 7.0 (0.05% w/v aqueous solution) at
`308C
`Surface tension 25.2 mN/m (25.2 dynes/cm) for a 0.05% w/v
`aqueous solution at 308C
`Wetting time (Draize test) 118 seconds (0.05% w/v aqueous
`solution) at 308C
`
`11 Stability and Storage Conditions
`Sodium lauryl sulfate is stable under normal storage conditions.
`However, in solution, under extreme conditions, i.e. pH 2.5 or
`below,
`it undergoes hydrolysis to lauryl alcohol and sodium
`bisulfate.
`The bulk material should be stored in a well-closed container
`away from strong oxidizing agents in a cool, dry place.
`
`12 Incompatibilities
`Sodium lauryl sulfate reacts with cationic surfactants, causing loss
`of activity even in concentrations too low to cause precipitation.
`Unlike soaps, it is compatible with dilute acids and calcium and
`magnesium ions.
`Sodium lauryl sulfate is incompatible with salts of polyvalent
`metal ions, such as aluminum, lead, tin or zinc, and precipitates with
`potassium salts. Solutions of sodium lauryl sulfate (pH 9.5–10.0)
`are mildly corrosive to mild steel, copper, brass, bronze, and
`aluminum.
`
`13 Method of Manufacture
`Sodium lauryl sulfate is prepared by sulfation of lauryl alcohol,
`followed by neutralization with sodium carbonate.
`
`652
`
`Sodium Lauryl Sulfate
`
`SEM 1: Excipient: sodium lauryl sulfate; manufacturer: Canadian Alcolac
`Ltd; magnification: 120.
`
`SEM 2: Excipient: sodium lauryl sulfate; manufacturer: Canadian Alcolac
`Ltd; magnification: 600.
`
`S
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`Table II: Pharmacopeial specifications for sodium lauryl sulfate.
`
`Test
`
`Identification
`Characters
`Alkalinity
`Heavy metals
`Sodium chloride and sodium sulfate
`combined content
`Unsulfated alcohols
`Nonesterified alcohols
`Total alcohols
`Water
`Assay (as C12H25NaO4S)
`
`PhEur 6.0 USP32–NF27
`JP XV
`þ
`þ
`þ
`þ
`—
`—
`þ
`þ
`þ
`40.002%
`—
`—
`48.0% 48.0% 48.0%
`
`44.0%
`44.0% —
`44.0% —
`—
`559.0% —
`559.0%
`45.0% —
`—
`585.0% —
`—
`
`10 Typical Properties
`Acidity/alkalinity pH = 7.0–9.5 (1% w/v aqueous solution)
`
`

`

`14 Safety
`Sodium lauryl sulfate is widely used in cosmetics and oral and
`topical pharmaceutical
`formulations.
`It
`is a moderately toxic
`material with acute toxic effects including irritation to the skin,
`eyes, mucous membranes, upper respiratory tract, and stomach.
`Repeated, prolonged exposure to dilute solutions may cause drying
`the skin; contact dermatitis may develop.(3)
`and cracking of
`Prolonged inhalation of sodium lauryl sulfate will damage the
`lungs. Pulmonary sensitization is possible, resulting in hyperactive
`airway dysfunction and pulmonary allergy. Animal studies have
`shown intravenous administration to cause marked toxic effects to
`the lung, kidney, and liver. Mutagenic testing in bacterial systems
`has proved negative.(4)
`Adverse reactions to sodium lauryl sulfate in cosmetics and
`pharmaceutical formulations mainly concern reports of irritation to
`the skin(3,5–7) or eyes(8) following topical application.
`Sodium lauryl sulfate should not be used in intravenous
`preparations for humans. The probable human lethal oral dose is
`0.5–5.0 g/kg body-weight.
`LD50 (mouse, IP): 0.25 g/kg(9)
`LD50 (mouse, IV): 0.12 g/kg
`LD50 (rat, oral): 1.29 g/kg
`LD50 (rat, IP): 0.21 g/kg
`LD50 (rat, IV): 0.12 g/kg
`
`15 Handling Precautions
`Observe normal precautions appropriate to the circumstances and
`quantity of material handled. Inhalation and contact with the skin
`and eyes should be avoided; eye protection, gloves, and other
`protective clothing, depending on the circumstances, are recom-
`mended. Adequate ventilation should be provided or a dust
`respirator should be worn. Prolonged or repeated exposure should
`be avoided. Sodium lauryl sulfate emits toxic fumes on combustion.
`
`16 Regulatory Status
`GRAS listed. Included in the FDA Inactive Ingredients Database
`(dental preparations; oral capsules, suspensions, and tablets; topical
`and vaginal preparations). Included in nonparenteral medicines
`licensed in the UK. Included in the Canadian List of Acceptable
`Non-medicinal Ingredients.
`
`17 Related Substances
`Cetostearyl alcohol; cetyl alcohol; magnesium lauryl sulfate; wax,
`anionic emulsifying.
`Magnesium lauryl sulfate
`Empirical formula C12H26O4S HMg
`CAS number
`[3097-08-3]
`Comments A soluble tablet lubricant.(10) The EINECS number for
`magnesium lauryl sulfate is 221-450-6.
`
`18 Comments
`Sodium lauryl sulfate is one of the materials that have been selected
`for harmonization by the Pharmacopeial Discussion Group. For
`further information see the General Information Chapter <1196>
`
`Sodium Lauryl Sulfate
`
`653
`
`in the USP32–NF27, the General Chapter 5.8 in PhEur 6.0, along
`with the ‘State of Work’ document on the PhEur EDQM website,
`and also the General Information Chapter 8 in the JP XV.
`A specification for sodium lauryl sulfate is contained in the Food
`Chemicals Codex (FCC).(11)
`The EINECS number for sodium lauryl sulfate is 205-788-1. The
`PubChem Compound ID (CID)
`for sodium lauryl sulfate is
`3423265.
`
`19 Specific References
`1 Smith BJ. SDS polyacrylamide gel electrophoresis of proteins. Methods
`Mol Biol 1994; 32: 23–34.
`2 Riekkola ML et al. Selectivity in capillary electrophoresis in the
`presence of micelles, chiral selectors and non-aqueous media. J
`Chromatogr 1997; 792A: 13–35.
`3 Wigger-Alberti W et al. Experimental irritant contact dermatitis due to
`cumulative epicutaneous exposure to sodium lauryl sulphate and
`toluene: single and concurrent application. Br J Dermatol 2000; 143:
`551–556.
`4 Mortelmans K et al. Salmonella mutagenicity tests II: results from the
`testing of 270 chemicals. Environ Mutagen 1986; 8(Suppl. 7): 1–119.
`5 Blondeel A et al. Contact allergy in 330 dermatological patients.
`Contact Dermatitis 1978; 4(5): 270–276.
`6 Bruynzeel DP et al. Delayed time course of irritation by sodium lauryl
`sulfate: observations on threshold reactions. Contact Dermatitis 1982;
`8(4): 236–239.
`7 Eubanks SW, Patterson JW. Dermatitis from sodium lauryl sulfate in
`hydrocortisone cream. Contact Dermatitis 1984; 11(4): 250–251.
`8 Grant WM. Toxicology of the Eye, 2nd edn. Springfield, IL: Charles C
`Thomas, 1974; 964.
`9 Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th
`edn. New York: Wiley, 2004; 3258–3259.
`10 Caldwell HC, Westlake WJ. Magnesium lauryl sulfate–soluble lubri-
`cant [letter]. J Pharm Sci 1972; 61: 984–985.
`11 Food Chemicals Codex, 6th edn.
`Bethesda, MD: United States
`Pharmacopeia, 2008; 892.
`
`20 General References
`European Directorate for the Quality of Medicines and Healthcare
`(EDQM). European Pharmacopoeia – State Of Work Of International
`Harmonisation. Pharmeuropa 2009; 21(1): 142–143. http://www.edq-
`m.eu/site/-614.html (accessed 3 February 2009).
`Hadgraft J, Ashton P. The effect of sodium lauryl sulfate on topical drug
`bioavailability. J Pharm Pharmacol 1985; 37(Suppl. 85P): .
`Nakagaki M, Yokoyama S. Acid-catalyzed hydrolysis of sodium dodecyl
`sulfate. J Pharm Sci 1985; 74: 1047–1052.
`Vold RD, Mittal KL. Determination of sodium dodecyl sulfate in the
`presence of lauryl alcohol. Anal Chem 1972; 44(4): 849–850.
`Wan LSC, Poon PKC. The interfacial activity of sodium lauryl sulfate in the
`presence of alcohols. Can J Pharm Sci 1970; 5: 104–107.
`Wang L-H, Chowhan ZT. Drug–excipient
`interactions resulting from
`powder mixing V: role of sodium lauryl sulfate. Int J Pharm 1990; 60:
`61–78.
`
`21 Author
`P Plumb.
`
`22 Date of Revision
`3 February 2009.
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