The „Fiedler - Encyclopedia of Excipients“, first published as a book by H. P. Fiedler in 1971, is now an up-to-date online system, which serves as a unique collection of information about excipients used in pharmacy, cosmetics and related fields. It offers more than 12'000 entries covering all excipients used in dosage forms. There are two different types of monographs:

 

1. Basic monographs giving general information on the properties of a substance and

2. Trademark monographs giving information on the specific properties and features of a marketed product, produced by a specific company.

 

Basic monographs refer to trademark monographs and vice versa. Both types of monographs follow the same scheme:

 

• Name of the monograph

• Companies producing the excipient

• Definition: Pharmacopoeial, INCI and chemical names, synonyms and trademarks, CAS/EINECS number, chemical structure and molecular weight

• Preparation: Short hint on synthesis or preparation method

• Properties: Appearance, solubility and density

• Product data: All other chemical and physico-chemical data available

• Applications: Main uses in pharmacy and cosmetics, illustrated by examples wherever possible

• Toxicology: Basic data on toxicology with focus on review articles

• Analytics: Hints on methods for the determination of the substance

• References: Literature citations of articles being of interest and not included into the single chapters of the monograph

 

Trademark monographs normally do not contain data on preparation, toxicology and analytics, because they do not differ from the general description in the corresponding basic monograph. Exceptions are possible, e. g., if there is a product only as one trademark available. The year of the last revision will be added to each monograph.

A manufacturers directory is added, giving the full address, including telephone and fax, as well as the internet an email links of the producer and its affiliates in Europe, North and/or South America and Asia. For each manufacturer the complete list of its excipients is given

In 2010, the “Fiedler - Encyclopedia of Excipients” was taken over by the Wissenschaftliche Verlagsgesellschaft Stuttgart, and from now it will be updated monthly. The authors/editors would like to thank Dr. Klaus G. Brauer, Dr. Eberhard Scholz and Mrs. Pia Rinker for their interest and effort to create a modern electronic data base on pharmaceutical and cosmetic excipients.

Ludwigshafen, Kelkheim and Nürnberg

S. Lang, A. K. Reng and P. C. Schmidt

The individual excipients are arranged alphabetically. The most customary spelling in scientific literature was chosen. An arrow (▸) means, that the following word is discussed in another section. Registered trademarks (®, TM) are omitted in the encyclopedia for the sake of clarity. This does not mean in any case that the appropriate word is available for common use. Temperature is given in degree Celcius (25° = 25℃) as far as not otherwise denoted.

 

For reasons of expediency several abbreviations are listed in the text and explained there.

°	℃, Centigrade degrees, Celcius degrees
a	anno = year
Å	Angström = 10–7 mm
AAS	atom absorption spectrometry
ACS	American Chemical Society
ADI	acceptable daily intake
ad lib	ad libitum
aq.	aqua = water
A.P.	American patent
APHA	American Public Health Association (color numbers)
at	atmosphere (tecn.), unit of pressure, 1 at = 1 kp/cm2
atm	atmosphere (physical.), unit of pressure, 1 atm = 1.033 kp/cm2
AcV	acetyl value
AV	acid value
bar	unit of pressure, 1 bar = 105 Pa
BET	method for measuring surface area according to Brunauer, Emmett and Teller
BGA	previous name of the German drug regulatory agency
BIS	Bibra Information Services (toxicity profiles)
bp	boiling point
BP	British Pharmacopeia
BPC	British Pharmaceutical Codex
cal	1 calorie = 4.1868 J
CAS	Chemical Abstracts Service Number
CG	cosmetic grade
C.I.	Colour Index (EU)
CIR	Cosmetic Ingredient Review
cKs	in the US occasionally taken for cSt
Cod Franc	Franc Codex Français
comp.	composition
cP	centiPoise (mPa∙s)
CPMP	Committee for Proprietary Medicinal Products of the EMEA
cSt	centiStoke
CFTA	Cosmetic, Toiletry, and Fragrance Association
d	density
dç	relative density
d	dies = day
d	dose
DAB	German Pharmacopoeia (Deutsches Arzneibuch)
DAC	German Drug Codex (Deutscher Arzneimittel Codex)
DAS	published examined German patent application (Deutsche Auslegeschrift)
DBP	German federal patent (Deutsches Bundespatent)
DGF	German society for fat science (Deutsche Gesellschaft für Fettwissenschaft)
dil.	dilutus = diluted
DIN	German institute for standardization (Deutsches Institut für Normung)
DL	dosis letalis
DLM	dosis letalis minima
DRP	former German patent (Deutsches Reichspatent)
E.	Engler grades, viscosimetry
EC	European Community
EINECS	European Inventory of Existing Chemical Substances
ELINCS	European List of Notified Chemical Substances
EMEA	European Medicines Evaluation Agency
E.P.	English patent
Erg B	German Pharmacopoeia, Supplement (Ergänzungsband zum Deutschen Arzneibuch)
et al.	et alii = and others
EV	ester value
°F	Fahrenheit degrees, see survey table Temperature Transformation
F Bras	Bras Farmacopéia das Estados Unidas da Brasil
FCC	Food Chemicals Codex
FDA	US Food and Drug Administration
fp	freezing point
FU	Farmacopeia Ufficiale della Republica Italiana
G	giga = 109
GC	gas chromatography
GDR	the former German Democratic Republic
Ger. Offen. (DE)	published unexamined German patent (DE) documentation; document laid open
GLC	gas liquid chromatography
GLP	good laboratory practice
GPC	gel permeation chromatography
h	hora = hour
HLB	hydrophilic-lipophilic balance
HPCE	high performance capillary electrophoresis
HPLC	high performance liquid chromatography
i.c.	intracutaneous
ICH	International Conference on Harmonization
i.m.	intramuscular
INCI	International Nomenclature of Cosmetic Ingredients
int.	internus = internal
i.p.	intraperitoneal
IP	The Pharmacopoeia of India
IR	infra-red
IRS	infra-red spectroscopy
I.U.	international unit
i.v.	intravenous
IV	iodine value
J	Joule, unit of energy, 1 J = m2 kg/s2 (Nm)
JCID	Japanese Cosmetic Ingredients Dictionary
JP	The Pharmacopoeia of Japan
JPE	Japanese Pharmacopoeia Excipients
JSCI	Japanese Standard of Cosmetic Ingredients
°K	Kelvin degrees, SI-unit of temperature, 273.15°K = 0℃
kcal	kilocalorie(s), unit of energy, 1 kcal = 4.1868 kJ
kJ	kiloJoule(s), unit of energy, 1 kJ = 0.239 kcal
l	liter(s), unit of volume 1 l = 1 dm3
loc. cit.	loco citato
LC	liquid chromatography
LD50	lethal dose for 50 %
LD lo	lowest published lethal dose in literature
LOD	loss on drying
M	molar, concentration unit e.g. 3M
MAC	Maximum Admissible Concentration (drinking water)
MAK	Maximale Arbeitsplatz-Konzentration
max.	maximum
mCi	milliCurie
µCi	microCurie
MEL	Maximum Exposure Limits
meq	milliequivalents/g
mg%	milligramm percent = mg of dissociated material in 100 g total mass (solvent)
min	minute(s)
min.	minimal, minimum
MITI	Ministry of International Trade and Industry (Japan)
MLD	minimum lethal dose
mmHg	millimeter(s) of mercury, unit of pressure, 1 mmHg = 133.322387415 Pa
Mn	number molecular weight, determined for polymers by osmometry
mol	mole(s), mass of 6.023∙1023 moles (g)
molwt	molecular weight
mp	melting point
mp*	melting point according to pharmacopoeial 'open capillary method'
mPa∙s	milliPascal seconds, unit of viscosity, 1 mPa∙s = 1 cP
MS	mass spectroscopy
mth	month
Mw	weight molecular weight, determined for polymers by light scattering or ultracentrifugation
n.	normal
n20	number of members of a statistical collective
nD	refractive index
NF	The US National Formulary
nm	nanomolar
nm	nanometer(s), unit of length, 1 nm = 10-9 m
nmol	nanomole(s) = 10-9 mol
NND	New and Nonofficial Drugs
NNR	New and Nonofficial Remedies
NRF	new prescription formulary (Neues Rezept-Formularium)
NTP	US National Toxicological Program
NV	neutralization value
ÖAB	Austrian Pharmacopoeia (Österreichisches Arzneibuch)
OECD	Organization for Economic Co-operation and Development
OEL	Occupational Exposure Limits
OHV	hydroxyl value
OS	see Ger. Offen.
OVIs	organic volatile impurities
O/W	oil-in-water (emulsion)
P	Poise, 1 P = 0.1 Pa∙s, dynamical viscosity
P.	granted patent, does not indicate that the patent is still valid at present
Pa	Pascal, unit of pressure, 1 Pa = m-1 kg s-2 (Nm-2)
PC	paper chromatography
PDA	Permitted Daily Exposure (Residual Solvents)
pH	the negative logarithm of the hydrogen ion concentration
Ph Belg	Pharmacopée Belge
Ph Dan	Pharmacopoea Danica
Ph F	Pharmacopoea Fennica
Ph Franc	Pharmacopoée Française
Ph Helv	Pharmacopoea Helvetica
Ph Ned	Pharmacopoea Nederlandica
Ph Nord	Pharmacopoea Nordica
Ph Norv	Pharmacopoea Norvegica
Ph Svec	Pharmacopoea Svecica
p.i.	post injectionem, infusionem = after injection, infusion
pM	picomolar
p.o.	per os = oral
PON	peroxide number
ppb	parts per billion
ppm	parts per million
prim.	primary
PV	peroxide value
RD	Recognised Disclosure numbers of CTFA
RH	relative humidity
RhV	Rhodane value
ROI	residue on ignition
RPHPLC	reversed phase high pressure liquid chromatography
s	second(s)
s.c.	subcutaneous
SDA	specially denaturated alcohol
sec.	secondary
SEM	scanning electron microscope
sp	solidification point
SSU	Saybolt universal second
St.	Stokes, 1 St. = 10−4 m2 s−1, kinematic viscosity
SV	saponification value
t	time
TD lo	lowest published toxic dose in literature
tert.	tertiary
TGA	Therapeutic Goods Administration (Australia)
TLC	thin layer chromatography
TLV	Threshold Limit Value
TSCA	Toxic Substances Control Act
U.	units
Ung.	unguentum
USP	The United States Pharmacopoeia
vol.	volume
vol-%	volume percent = 1 ml of dissociated material in 100 ml solution
W/O	water-in-oil (emulsion)
wt	weight

As a result of international agreements a unification of the measurement system has been achieved (International System of Units; Système international = SI-units). In Germany the “Law on Units in the Measurement System” was passed on 2 July 1969, the implementing ordinance concerning this Law was passed on 26 July 1970 and a Law for amending the Law on Units in the Measurement System on 6 July 1973. According to this legal framework the unitsdefined in these laws and regulations are obligatory for business and official transactions. Details have been defined in DIN 1301 “Units, unit names, unit symbols” (DIN Deutsches Institut für Normung e. V., Burggrafenstraße 6, 10787 Berlin, Tel.: +49 30 2601-0, Fax: +49 30 2601-1231 and in ISO 31, which is now superseded by the harmonized ISO/IEC 80000 standard (ISO copyright office, Case postale 56, CH-1211 Geneva 20, Tel. + 41 22 749 01 11, Fax + 41 22 749 09 47.

In the USA the same units etc. were first described in The Metric Conversion Act of 1975 (Public Law 94–168) (see also G.G. Stoner, Cosmet. Toiletries 93, No. 11, 57 [1978]) and are now harmonized in ISO 80000.

The new units have been taken into account in the present edition of the Handbook, when new documentation has been provided by the manufacturers of auxiliary substances. The new units have also been used in some revisions and additions by the editors. However, in the following the most important changes in the measurement system are given so that conversions from older unit systems may be performed, if required.

There are nine basic SI units, of which the following 7 are relevant:

 

SI-Basic Units

 

Basis physical quantity	Basic unit
	Name	Symbol
length	meter	m
time	second	s
mass	kilogram	kg
temperature	kelvin	K
electrical current	ampere	A
luminous intensity	candela	cd
amount of substance	mole	mol

17 further units are derived from the nine basic units, of which the following derived SI units, with their names,are relevant:

 

Physical quantity	Unit		Expressed as basic units or derived units
	Name	Symbol
work, energy, quantity of heat	joule	J	1J = 1Nm = 1(kg*m2)/s2 = 1Ws
illuminance	lux	lx	1lx = 1 lm//m2
force	Newton	N	1N = 1 (kg*m)/s2
pressure	Pascal	Pa	1 Pa = 1N/m2 = 1kg/(m*s2)

The following prefixes were established for decimal multiples and subdivisions of units:

Multiples	Prefix	Symbol	Subdivisions	Prefix	Symbol
101	deca	da	10–1	deci	d
102	hecto	h	10–2	centi	c
103	kilo	k	10–3	milli	m
106	mega	M	10–6	micro	µ
109	giga	G	10–9	nano	n
1012	tera	T	10–12	pico	p
1015	peta	P	10–15	femto	f
1018	exa	E	10–18	atto	a

 

Spelling conventions for SI Units

 

If derived units consist of several basic units in the numerator or denominator, these are written one after the other with some space in between (in the case of a typewriter a single space).

Examples: N s/m, not Ns/m; kg m/s, not kgm/s.

However, multiples or subdivisions are written together with the respective units.

Examples: MNm, not M N m; mm²/s, not m m²/s.

Indices must not be appended to unit symbols but should be added to the formula symbol giving the physical quantity. Hence e.g. the normal volume may no longer be given as Nm³ (normal cubic meter) but instead as: normal volume V_n=…m³ or better: volume V=…m³ in the normal state.

Variations are permissible in the names for physical quantities, but the standard form of the unit name should always be used. This principle helps to avoid misleading spellings.

Data for the various units relevant to the present Handbook, or the corresponding conversion factors for previously used units, are given in the following table:

 

Legal Units

 

Physical quantity	Legal units				Conversion		Comment
	Symbol	SI Unit		Relationship	Recommended unit	Previous unit
		Name	Symbol
mass	m	kilogram	kg	1g = 10-3kg; 1t = 103kg	kg		SI basic unit
density	ρ	kilogram per cubic meter	kg/m3		g/cm3; kg/m3
specific volume	V	cubic meter per kilogram	m3/kg		cm3/g; m3/kg
amount of substance	n	mole	mol		kmol
mass related to amount of substance (molar mass)	M	kilogram per mol	kg/mol		kg/kmol
volume related to amount of substanc (molar volume)	Vm	cubic meter per mole	m3/mol		m3/kmol
surface tension and interfacial tension		milli-Newton per meter	mN/m		mN/m	dyn/cm	for all liquids
thermodynamic or kelvin temperature, celsius temperature	T, Θ, t, ϑ	Kelvin	K	t = T -273K	K ℃	°K	SI basic unit practical conversion:  t = T -273K
dynamic viscosity	η	Pascal second	Pa·s		mPa·s	cP (centipoise)
kinematic viscosity	ν	square meter per second	m2/s		cm2/s	st (stokes)

 

 

Conversion of the most common British (UK) and American (US) Units into SI Units

 

Physical quantity	Name of the unit	Symbol	Conversion into SI Units
length	inch	in	1in	=25.4mm
	foot	ft	1ft=12in	=0.3048m
	yard	yd	1yd=3ft	=0.9144m
	mile (statute)		1mile=1760yd	=1.609344km
	nautical mile (intern.)	n. mile	1n. mile	=1.852km
area	square inch	sq in	1sq in	=6.4516cm2
	square foot	sq ft	1sq ft=144sq in	=929.030cm2
	square yard	sq yd	1sq yd=9sq ft	=0.836127m2
	rood		1rood=1210sq yd	=1011.71m2
	acre		1acre=4roods	=4046.86m2
	square mile	sq mile	1sq mile=640acres	=2.589988km2
volume	cubic inch	cu in	1cu in	=16.3871cm3
	cubic foot	cu ft	1cu ft	=28.3168dm3
	cubic yard	cu yd	1cu yd	=0.764555m3
British measure of capacity	UK fluid ounce	UK fl oz	1fl oz	=28.4131cm3
	UK gill		1gill=5fl oz	=0.142065dm3
	UK pint	UK pt	1pt=20fl oz	=0.568261dm3
	UK quart	UK qt	1qt=2pt	=1.13652dm3
	UK gallon	UK gal	1gal=4qt	=4.54609dm3
American measure of capacity (liquid)	US fluid ounce	US fl oz	1fl oz	=29.5735cm3
	US gill	gi	1gi=4fl oz	=0.118294dm3
	US liquid pint	liq pt	1liq pt=4gi	=0.473176dm3
	US liquid quart	liq qt	1liq qt=2liq pt	=0.946353dm3
	US gallon	US gal	1gal=4liq qt	=3.78541dm3
	US barrel (oil)	bbl	1bbl=42gal	=158.987dm3
American measure of capacity (dry)	US dry pint	dry pt	1dry pt	=0.550610dm3
	US dry quart	dry qt	1dry qt=2dry pt	=1.10122dm3
	US peck	pk	1pk=8dry qt	=8.80976dm3
	US bushel	bu	1bu=4pk	=35.2391dm3
mass	grain	gr	1gr	=0.064799g
	dram (avoir dupois)	dr	1dr=27.34375gr	=1.77185g
	ounce (avdp.)	oz	1oz=16dr	=28.3495g
	troy ounce	oz tr	1oz tr=480gr	=31.1035g
	pound (avdp.)	lb	1lb=16oz	=0.453592kg
	troy pound	lb tr	1lb tr=12oz tr	=0.373242kg
	stone (UK)		1stone=14lb	=6.35029kg
	hundredweight (UK)	cwt	1cwt=112lb	=50.8023kg
	(long) ton (UK)	ton	1ton=2240lb	=1016.05kg
	Shorthundredweight (US)	sh cwt	1sh cwt=100lb	=45.3592kg
	short ton (US)	sh ton	1sh ton=2000lb	=907.185kg
force	poundal	pdl	1pdl=1lb ft/s2	=0.138255N
	pound-force	lbf	1lbf	=4.44822N
	UK ton-force	UK tonf	1tonf=2240lbf	=9964.02N
	US ton-force=2kip	US tonf	1tonf=2000lbf	=8896.44N
pressure	pound-force / sq ft	lbf / ft2	1lbf / ft2	=47.8803Pa
	pound-force / sq in (p.s.i.)	lbf / in2	1lbf / in2	=6.89476kPa
energy, quantity of heat	foot pound-force	ft lbf	1ft lbf	=1.35582J
British thermal unit	Btu	1Btu	=1.05506kJ
therm		1therm=105 Btu	=105.506MJ
power	British thermal unit / hour	Btu / h	1Btu / h	=0.293071W
	horsepower	hp	1hp=550ft lbf / s	=745.700W
temperature	degree Fahrenheit	°F	temp. in ℃ =(temp. in °F −32)·5/9	∆1°F=∆5/9℃

Sieves are used to classify powders and granules in production and for analytical purposes. They are specified according to DIN/ISO 565 which is equivalent to ISO 3310-1. The following table, which is based on the USP text, compares the ISO sieves with those mentioned in Ph. Eur. and Japan. The US sieve numbers (mesh) are provided in the table for conversion purposes only.

ISO Nominal Aperture
Principal sizes	Supplementary sizes	Recommended USP sieves	US sieve no. (mesh)	Ph. Eur. sieve no.	Japan sieve no.
11.20mm				11200
5.60mm				5600	3.5
	4.75mm				4
4.00mm		4000	5	4000	4.7
	3.35mm		6		5.5
2.80mm		2800	7	2800	6.5
	2.36mm		8		7.5
2.00mm		2000	10	2000	8.6
	1.7mm		12		10
1.40mm		1400	14	1400	12
	1.18mm		16		14
1.00mm		1000	18	1000	16
	850µm		20		18
710µm		710	25	710	22
	600µm		30		26
500µm		500	35	500	30
	425µm		40		36
355µm		355	45	355	42
	300µm		50		50
250µm		250	60	250	60
	212µm		70		70
180µm		180	80	180	83
	150µm		100		100
125µm		125	120	125	119
	106µm		140		140
90µm		90	170	90	166
	75µm		200		200
63µm		63	230	63	235
	53µm		270		282
45µm		45	325	45	330
	38µm			38	391

 

References

USP/NF (786) Particle size distribution estimation by analytical sieve testing, USP32/NF27, 307 (2009).

Ph. Eur. 2.1.4 Sieves, Kommentar Ph. Eur. 4.00, 2.1.4 Siebe (2004).

J. Goede, Verarbeitung von Stoffen/Trennen, in E. Nürnberg and P. Surmann (eds.), Hagers Handbuch der Pharmazeutischen Praxis, 5^th ed., vol. 2 Methods, p. 586-587, Springer, Berlin, Heidelberg, New York (1991).

Guideline on the Excipients in the Label and Package Leaflet of Medicinal Products for Human Use

Volume 3B Guidelines, July 2003

Pursuant to Article 65 of European Council Directive 2001/83/EC

Annex: Excipients and Information for the Package Leaflet

www.emea.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003412.pdf

Explanatory Notes: The Annex is structured as follows:

Name: This is the name of the excipient using INN or PhEur nomenclature where possible, including a reference to E-numbers where relevant.

Route of administration: This is necessary because the information may depend upon the route of administration, e.g. for benzalkonium chloride the information relating to bronchospasm is relevant only for the respiratory route.

Threshold: It is accepted that excipients may only show an effect above a certain ‘dose’.

Except where otherwise stated, thresholds are expressed as Maximum Daily Doses of the excipient in question, taken as part of a medicinal product.

The threshold is a value, equal to or above which it is necessary to provide the information stated.

A threshold of ‘zero’ means that it is necessary to state the information in all cases where the excipient is present in the medicinal product.

Information for the Package Leaflet: The information is presented here in a simple form, in clear and understandable terms for the patient.

The text often refers to the term ‘per dose’ meaning dose of the medicinal product.

Since doses may be extremely variable, applicants must take into account the maximum single dose of the medicinal product, as defined in the SPC, Section 4.2.

For this reason the information sometimes contains the expression ‘up to x mg per dose’, for example.

If the pharmaceutical form is a solid form, e.g. tablet, capsule, suppository, powder in a sachet, it may be better to refer to the amount per tablet, capsule etc.

The Cosmetic Ingredient Review was established in 1976 by the industry trade association (then the Cosmetic, Toiletry, and Fragrance Association, now the Personal Care Products Council), with the support of the U.S. Food and Drug Administration and the Consumer Federation of America. Although funded by the Council, CIR and the review process are independent from the Council and the cosmetics industry.

The Cosmetic Ingredient Review thoroughly reviews and assesses the safety of ingredients used in cosmetics in an open, unbiased, and expert manner, and publishes the results in the open, peer-reviewed scientific literature.

Cosmetic Ingredient Review
1101 17th Street N. W., Suite 412
Washington DC 20036-4702 (USA)
Tel. +1-202-331-0651
Fax +1-202-331-0088

Further informations: Publications, ingredient reports, quick reference table: www.cir-safety.org/publications.shtml

The BIBRA Toxicity Profiles are critical reviews of the most pertinent toxicological data published on commercially important chemicals. Prepared by experienced toxicologists, each Profile is compiled principally from primary sources, as a comprehensive yet succinct evaluative summary. The Toxicity Profile project has been running for over 20 years, and BIBRA has now built up a formidable series of monographs covering neraly 500 chemicals.

Products an services, Toxicity profiles, search for specific profiles, list of all profiles avaible: www.bibra-information.co.uk

Note for Guidance on Impurities: Residual Solvents

The European Agency for the Evaluation of Medicinal Products Human Medicines Evaluation Unit

CPMP/ICH/283/95, March 1998, ICH Harmonised Tripartite Guideline Q3C

The limits for residual solvents given in Ph Eur, USP and JP are based on the Guidelines for Residual Solvents (CPMP/ICH/283/95, March 1998) which were adopted by the International Conference on Harmonization (ICH) for registration of pharmaceuticals for human use and prescribe limits for the content of solvents which may retain in active substances, excipients and medicinal products after processing. The residual solvents are listed in Appendix 1 by common names and structures. They were evaluated for their possible risk to human health and placed into one of three classes as follows:

Class 1 solvents: Known human carcinogens, strongly suspected human carcinogens, and environmental hazards. They are listed in Table 1.

Class 2 solvents (solvents to be limited): Non-genotoxic animal carcinogens or possible causative agents of other irreversible toxicity such as neurotoxicity or teratogenicity. They are listed in Table 2.

Class 3 solvents (solvents with low toxic potential): Solvents with low toxic potential to man; no health-based exposure limit is needed. Class 3 solvents have PDEs of 50mg or more per day. They are listed in (Definition of PDE: Permitted daily exposure).

Further information: www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002674.pdf and www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000431.jsp&jsenabled=true

Water legislation in the EU is based on the Council Directive 98/83/EC of November, 3, 1998 on the quality of water intended for human consumption; Official Journal L 330, 05/12/1998, p.0032-0054.

Parameters and parametric values are presented in Annex I: eur-lex.europa.eu/LexUriServ/LexUriServ.do

Coloring Agents for Cosmetic Products in the USA, Japan and EU

The coloring of cosmetic products is regulated by law in the USA, Japan and the European Union. Other countriesoften use the regulations of these countries as a model. The following references can be used for further information.

Blue List: Cosmetic Ingredients, ECV Editio Cantor Verlag, Aulendorf (2000); G. Otterstätter, Die Färbung von Lebensmitteln, Arzneimittel, Kosmetika, Behr's Verlag, Hamburg (1995); C. Fox, Color in Cosmetics, Cosmetics & Toiletries 111 (3), 35 (1996); G. Otterstätter, Die Färbung von Kosmetika, SÖFW-Journal 123, 328 (1997); G. Otterstätter, Kosmetische Färbemittel im internationalen Vergleich, Parfümerie und Kosmetik 78 (10), 8 (1997); R. Romanowski and R. Schüeller, Creating Colorful Cosmetics, Cosmetics & Toiletries 112 (9), 73 (1997); D. C. Steinberg, Regulatory Review, Cosmetics & Toiletries 111 (10), 29 (1996); CTFA Color Handbook 1992, Cosmetic, Toiletry and Fragrance Association, Inc., 1101 17^th Street, NW, Suite 300, Washington, D.C. 20036-4702, USA; Principles of cosmetic licensing in Japan, 2^nd Edition; Yakuji Nippo Ltd. 1, Kanda Izumicho, Chiyoda-Ku, Tokyo, 101, Japan.

The coloring agents authorized in the USA for coloring cosmetic products are listed in the Code of Federal Regulations 21 (CFR 21), which can be ordered from the U.S. Government Printing Office, Superintendent of Documents, Mail Stop: SSOP. Washington, DC 20402-9328.

Furthermore a summary of color additives listed for use in the United States in foods, drugs, cosmetics, and medical devices is given by the following address: Office of Food Additive Safety (HFS-200), Center for Food Safety and Applied Nutrition, Food and Drug Administration, 5100 Paint Branch Parkway, College Park, MD 20740-3835, USA.

Further information: ec.europa.eu/consumers/cosmetics/cosing/index.cfm

 

Coloring Agents for Cosmetic Products in Germany

www.gesetze-im-internet.de/bundesrecht/kosmetikv/gesamt.pdf

 

Coloring Substances in Drugs

The use of coloring substances in medicaments is regulated by the Council Directive 94/36/EEC, June 30, 1994, originally designed for colors in food. It is completed by the Council Directive 95/45/EEC, July 26, 1995 on purity of food colors. The list (Appendix I) contains the following substances:

Appendix I

Colour shade EEC No.	Name	Chemical name or description
Yellow
E 100	Curcumin	1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadien-3,5-dione
E 101	Riboflavin (Lactoflavin)	7,8-dimethyl-10-(1'-D-ribityl)isoalloxazin
E 102	Tartrazine	5-hydroxy-1-(4-sulfophenyl)-4-(4-sulfophenylazo)-3-pyrazol-carboxylic acid, trisodium salt
E 104	Quinoline yellow	2-(1,3-dioxo-2-indanyl)quinoline disulfonic acid, disodiumsalt (also containing monosulfonic acid derivatives, also partly methylated)
Orange
E 110	Yellow orange S (Sunset yellow FCF)	6-hydroxy-5-(4-sulfophenylazo)-2-naphthalene-sulfonic acid, disodium salt
Red
E 120	Carmine (Cochineal carminic acid)	extract from Dactylopius coccus [syn. Coccus cacti] including the ammonium salts
E 122	Azorubin (Carmoisine)	1'-hydroxy-1,2'-azonaphthalene-4,4'-disulfonic acid, disodium salt
E 123	Amaranth	2-hydroxy-1,1'-azonaphthalene-3,4',6-trisulfonic acid, trisodium salt
E 124	Ponceau 4R (Cochineal Red A)	2-hydroxy-1,1'-azonaphthalene-4',6,8-trisulfonic acid, trisodium salt
E 127	Erythrosine	2',4',5',7'-tetraiodofluorescein, disodium salt or 2-(6-hydroxy-2,4,5,7-tetraiodo-3-oxo-3H-xanthene-9-yl)benzoic acid, disodium salt
E 128	Red 2G	disodium-8-acetamido-1-hydroxy-2-phenylazo-naphthalene-3,6-disulfonate
E 129	Allulared AC	disodium-2-hydroxy-1(2-methoxy-5-methyl-4-sulfo-phenyl- azo)-naphthalene-6-sulfonate
Blue
E 131	Patent Blue V	α-(4-diethylaminophenyl)-α-(4-diethylimino-2,5-cyclohexadiene-1-ylidene)-5-hydroxy-4-sulfo-o-toluenesulfonate, calcium salt
E 132	Indigo carmine (Indigotin)	3,3'-dioxo[∆2,2'-biindoline]-5,5'-disulfonic acid, disodium salt
E 133	Brilliant Blue FCF	disodium-α-(4-(N-ethyl-3-sulfobenzylamino)phenyl)-α-(4(N-ethyl-3-sulfobenzylamino)cyclohexa-2.5-diethylidene) toluene-2-sulfonate
Green
E 140	Chlorophyll	Chlorophyll a and Chlorophyll b
E 141	Chlorophyll- and Chlorophyllin- copper-complexes	Chlorophyll a(b)-copper-complexes and Chlorophyllin a(b)-copper-complexes
E 142	Acid brilliant green BS (Wool GreenBS, Lissamine green)	1-(α-(4-dimethylimino-2,5-cyclohexadiene-1-ylidene)-4-dimethylaminobenzyl)-2-hydroxy-6-sulfo-3-naphthalenesulfonate, sodium salt
Brown
E 150	Caramel	Product manufactured from sucrose (or other kinds of sugar suitable for consumption) solely by heating, or amorphous, brown, water-soluble products manufactured by controlled heating of edible sugars in the presence of acetic, citric, phosphoric or sulfuric acid, sulfur dioxide, ammonium-, sodium- and potassium hydroxide, -carbonate, -phosphate, -sulfate or -sulfite.
	a) Simple caramel	Prepared by controlled heating of carbohydrates.
	b) Sulfite caramel	Prepared by controlled heating of carbohydrates under the addition of sodium or potassium sulfite or bisulfite.
	c) Ammonia caramel	Prepared by controlled heating of carbohydrates under the addition of ammonia compounds like ammonium hydroxide, ammonium hydrogen carbonate or ammonium carbonate.
	d) Ammonium sulfite caramel	Prepared by controlled heating of carbohydrates under the addition of sulfite and ammonia compounds.
E 154	Brown FK	A mixture of the following main components: I. sodium-4-(2,4-diaminophenylazo)benzene sulfonate II. sodium-4-(4,6-diamino-m-tolylazo)benzene sulfonate III. disodium-4,4'-(4,6-diamino-1,3-phenylenebisazo)-di-benzenesulfonate IV. disodium-4,4'-(2,4-diamino-1,3-phenylenebisazo)-di-benzenesulfonate V. disodium-4,4'-(2,4-diamino-5-methyl-1,3-phenylenebisazo)-di-benzenesulfonate VI. trisodium-4,4',4''-(2,4-diaminobenzene-1,3,5-trisazo) tribenzenesulfonate
	Brown HT	disodium-4,4'-(2,4-dihydroxy-5-hydroxymethyl-1,3-phenylenebisazo)-di-naphthalene-1 sulfonate
Black
E 151	Brilliant Black BN	4-sulfophenylazo-4-(7-sulfonaphthalene)-1-azo-2-(8-acet- amido-1-hydroxy-3,5-naphthalenedisulfonic acid), tetrasodium salt
E 153	Carbon Black (Carbo medicinalis vegetabilis)	Vegetable charcoal having the properties of medicinal char coal
Various colours
E 160	Carotinoids:
	a) β,ε-Carotene (α''-Carotene) Betacarotene (β,β-Carotene) β,ψ -Carotene (γ-Carotene)	all-trans forms as main components
	b) Bixin, Norbixin (Annatto, Orlean)	Annatto is an extract of the seeds of Bixa orellana; the extract in oil is the carotinoid Bixin, the mono methyl ester of 6,6'-diapo-6,6'-carotene-dioic acid. Norbixin is the free dicarboxylic acid; the main colouring substance of the aqueous Annatto extracts is the alkali salt of Norbixin.
	c) Capsanthin, Capsorubin	Extract from paprika (Capsicum annuum fruits)
	d) Lycopene	ψ,ψ-Carotene (all-trans-form as main constituent)
	e) 8'-Apo-β,ψ-carotenal	8'-apo-β,ψ-carotenal (all-trans-form as main constituent)
	f) Ethyl-8'-apo-β,ψ-carotenoate	ethyl-8'-apo-β,ψ-carotenoate (all-trans-form as main constituent)
E 161	Xanthophylls:	Xanthophylls are keto- and/or hydroxy-derivatives of carotenes
	a) Flavoxanthin	5,8-epoxy-5,8-dihydro-β,β-carotene-3,3'-diol
	b) Lutein	β,ε-carotene-3,3'-diol
	c) Cryptoxanthin	β,β-carotene-3-ol
	d) Rubixanthin	β,ψ-carotene-3-ol
	e) Violaxanthin	5,6,5',6'-diepoxy-5,5',6,6'-tetrahydro-β,β-carotene-3,3'-diol
	f) Rhodoxanthin	4',5'-didehydro-4,5-retro-β,β-carotene-3,3'-dione
	g) Canthaxanthin	β,β-carotene-4,4'-dione
E 162	Beetroot Red, Betanin	aqueous extract from the root of the red beet (Beta vulgaris var. conditiva)
E 163	Anthocyanins	Anthocyanins are glycosides of hydroxylated derivatives of2-phenylbenzopyrylium salts; they contain the following anthocyanidins as aglycones: Pelargonidin, Cyanidin, Paeonidin (Peonidin), Delphinidin (Oenantidin), Petunidin, Malvidin. Anthocyanins must only be obtained from edible fruit or vegetables such as strawberries, mulberries, cherries, plums, raspberries, blackberries, black and red currants, red cabbage, red onions, cranberries, huckleberries, aubergines, grapes and elderberries.
E 170	Calcium carbonate	CaCO3
E 171	Titanium(IV)-oxide (Titanium dioxide)	TiO2
E 172	Iron oxides and -hydroxides	xFe2O3 · yFeO · nH2O
E 173	Aluminum	Al
E 174	Silver	Ag
E 175	Gold	Au

 

For the substances with the EEC numbers E 102, E 104, E 110, E 122 to E 124, E 127, E 131, E 132, E 142 and E 151 the acid on which the compound is based and any sodium, calcium, potassium and aluminum salt of this substance islicensed in addition to the sodium or calcium salt of the substance which is given in the column “Chemical name orDescription”.

Synthetic colouring substances which are identical to the natural colouring substances mentioned are also authorized.

Preservatives by Frequency of Use in Cosmetic Formulations

The use of preservatives for cosmetic purposes is regulated in the EU by the Commission Directive 2007/17/EC of 22 March 2007, amending Council Directive 76/768/EEC, concerning cosmetic products, for the purposes of adapting Annexes III and VI.

eur-lex.europa.eu/Notice.do

The Annex VI of the Council Directive 76/768/EEC can be found under

borealischem.com/pdf/Annex6%20Parts1-2PreservativesList.pdf

In the US preservatives are registered by the FDA.

In Japan the use of preservatives in cosmetics is regulated by the “Standards for Cosmetics” (Ministry of Health and Welfare Notification No.331 of 2000), Appendix 3, see also

www.mhlw.go.jp/english/topics/cosmetics/index.html

The frequency of use of preservatives in the US in 2005 is given in the following table.

 

Preservative	Frequency of use (2005)
Methylparaben	7866
Propylparaben	6260
Butylparaben	2784
Ethylparaben	2310
Phenoxyethanol	2227
Imidazolidinyl urea	2036
Sodium sulfite	1306
Resorcinol	1176
DMDM hydantoin	1062
Diazolidinyl urea	737
Methylchloroisothiazolinone/methylisothiazolinone 818	699
Sorbic acid/potassium sorbate	639
Benzoic acid/Sodium benzoate	582
Dehydroacetic acid/Sodium dehydroacetate	559
Quaternium-15	515
Isobutylparaben	507
Benzyl alcohol	502
Triclosan	484
Boric acid/sodium borate	353
Iodopropynyl butylcarbamate	195
2-Bromo-2-nitropropane-1,3-diol	187
Sodium methylparaben	160
Salicylic acid	140
Methyldibromo glutaronitrile	115
Formaldehyde	113
Benzalkonium chloride	82
Chlorhexidine digluconate	68
Sodium bisulfite	62
Chlorphenesin	58
Hexamidine isethionate	47
Isopropylparaben	47
Chloroxylenol	44
Chloroacetamide	36
Sodium hydroxymethylglycinate	35
5-Bromo-5-nitro-1,3-dioxane	34
Benzethonium chloride	32
Sodium propylparaben	30
Methenamine	28
o-Phenylphenol/Sodium-o-phenylphenol	28
Phenethyl alcohol	28
Grapefruit Seed Extract	23
Triclocarban	22
Paraformaldehyde	21
Glutaraldehyde (Glutaral)	19
Polymethoxy bicyclic oxazolidine	19
Chlorhexidine dihydrochloride	18
o-Cymen-5-ol	18
Thymol	13
Piroctone olamine	12
Dichlorobenzyl alcohol	11
Chlorhexidine acetate	9
Climbazole	9
Formic acid and salts	7
Hinokitiol	7
Domiphen bromide	6
Phenoxyisopropanol	6
Dichlorophene	5
p-Chloro-m-cresol	5
Phenyl mercuric acetate	5
Thiomersal	5
Undecylenic acid and salts	4
Dimethyloxazolidine	2
Polyaminopropyl biguanide	2
Benzylparaben	1
Chlorhexidine	1
7- Ethylbicyclooxazolidine	1
Total formulations reported	22228

Reference: D. C. Steinberg, 2005 Preservatives use: Frequency reports and registration, Cosmetic and Toiletries magazine 121(7), 65-69 (2006).

Emollients by Frequency of Use in Cosmetics in USA

Cited from: D.C. Steinberg, Cosmet. Toiletries 112, No 6, 31 (1997)

Emollient	Frequency of use (1996)
Cetyl alcohol	2860
Dimethicone	1898
Mineral oil, heavy	1847
Mineral oil, light	1695
Carnauba wax	1309
Beeswax, white	1244
Isopropyl myristate	1171
Stearyl alcohol	1129
Cyclomethicone	1056
Castor oil	976
Octyldodecanol	855
Cetearyl alcohol	847
Lanolin	838
Caprylic/Capric triglyceride	774
Candelilla wax	773
Petrolatum, yellow	761
Ozokerite	730
Polyethylene	647
Lanolin oil	646
Isopropyl palmitate	616
Paraffin	590
Squalane	581
Petrolatum, white	549
Octyl palmitate	533
Japan wax	513
Isopropyl lanolate	494
Microcrystalline wax	467
Oleyl alcohol	438
Acetylated lanolin alcohol	411
Hydrogenated vegetable oil	406
Sweet almond oil	399
Ceresin	347
Wheat germ oil	331
Jojoba oil	330
C12-15 alcohols benzoate	298
Sesame oil	287
Cetearyl octanoate	272
Hydrogenated cottonseed oil	272
Coconut oil	268
Cetyl palmitate	263
Wheat germ glycerides	259
Avocado oil	249
Myristyl myristate	249
Polybutene	241
Corn oil	231
Myristyl lactate	224
Cetyl acetate	218
Cetyl esters wax	217
Trilaurin	216
Hydrogenated castor oil	211
Shea butter	208
Propylene glycol dicaprylate/caprate	202
Synthetic jojoba oil	199
Beeswax, yellow	196
Decyl oleate	187
Acetylated lanolin	183
Hydrogenated polyisobutene	164
Synthetic beeswax	156
Cocoa butter	151
Hydroxylated lanolin	144
Soybean oil	141
Hydrogenated lanolin	133
Mink oil	131
Sunflower oil	131
Safflower oil	128
Stearyl heptanoate	128
Macadamia nut oil	127
Olive oil	124
Diisostearyl malate	121
Hydrogenated tallow	120
Apricot kernel oil	119
Lanolin wax	118
Hazelnut oil	105
Octyl hydroxystearate	104
Isopropyl isostearate	103
Borage oil	101

Table of Contents

 

1 Anionic Surfactants

• 1.1 Salts and Esters of Carboxylic Acids
• 1.2 Sulfuric Acid Derivatives
• 1.3 Sulfonic Acids and Salts
• 1.4 Phosphoric Acid Esters and Salts
• 1.5 Acylamino Acids and Salts

2 Cationic Surfactants

2.1 Alkyl Amines

• 2.2 Alkylimidazolines
• 2.3 Quaternary Ammonium Compounds
• 2.4 Ethoxylated Alkyl Amines
• 2.5 Esterified Quaternaries

3 Amphoteric Surfactants

• 3.1 Acyl Ethylenediamines and Derivatives
• 3.2 N-Alkyl Amino Acids or Imino Diacids
• 3.3 Alkyl Betaines

4 Nonionic Surfactants

• 4.1 Fatty Alcohols
• 4.2 Ethers
• 4.3 Alkanolamides
• 4.4 Esters
• 4.5 Ester/Ether Surfactants
• 4.6 Amine Oxides

5 Alkoxylated Polysiloxanes

6 Fluorosurfactants

Comparison of the Properties of Various Surfactant Types

Surfactants, Preferably Used in the Manufacture of Pharmaceuticals and/or Cosmetics

The classification given below is a modified version of a review presented by L. O. de Guertechin (in G. Broze, Handbook of Detergents (Surfactant Series Vol. 82), Part A: Properties, pp. 7–46, Marcel Dekker Inc., New York and Basel 1999).

 

1 Anionic Surfactants

1.1 Salts and Esters of Carboxylic Acids

1.1.1 Carboxylic Acid Salts (Soaps)

Free fatty acids are not used as surfactants, due to their low water solubility. However water-soluble fatty acid salts like alkali and short-chain amine salts (ethanol amine, diethanol amine, triethanol amine) show good water affinity and are widely used. Saturated sodium soaps are extremely soluble in water up to C₈ (these are not yet true surfactants); they become less soluble up to C₁₈ (i.e., the domain of effective surfactants) and insoluble above C₂₀. The fatty acids can be either saturated or unsaturated, starting from C₁₆chain lengths. Unsaturated fatty acids are prone to undergo oxidation and form oxides and peroxides which cause rancidity and yellowing. Potassium soaps and salts of alkanolamines are more fluid and also more soluble than sodium salts.

Fatty acid alkali salts (R = C₇H₁₅ −C₁₇H₃₅)

Fatty acid earth alkali salts (R = C₇H₁₅ −C₁₇H₃₅)

Fatty acid ethanol amine salts (R = C₇H₁₅ −C₁₇H₃₅)

Fatty acid isopropanol amine salts (R = C₇H₁₅ −C₁₇H₃₅)

 

Applications.
The main application of fatty acid salts is found in the soap bars used worldwide for hand-washing fabrics (generally based on tallow/coconut oil mixtures). Water-soluble soaps are mainly used in skin cleansers (soap bars or liquids), shaving products (sticks, foams, or creams), and deodorant sticks. Water-insoluble soaps form gels in nonaqueous systems and, due to their hydrophobicity, they can be appropriate surfactants or thickeners for w/o emulsions. Some of them are used as lubricants (e.g. magnesium stearate and calcium arachinate).

 

1.1.2 Ester Carboxylic Acids

They are monoesters of di- and tricarboxylic acids. These esters are produced by condensation reactions involving different types of molecules: either an alcohol with a polycarboxylic acid (e.g., tartaric or citric acid), or an hydroxyacid (e.g., lactic acid or citric acid) with a carboxylic acid. The alcohol may have been previously ethoxylated to enhance water solubility and surface activity.

Sodium dilaureth-7-citrate

Stearoyl disodium tartrate

Applications.
Due to their good foaming properties and substantivity on the hair, ester carboxylates are especially suitable in shampoos; in combination with alcohol ethoxy sulfates, they reduce skin irritation.

 

1.1.3 Ether Carboxylic Acids

These surfactants are formed by the reaction of sodium chloracetate with ethoxylated alcohols. Due to the addition of ethoxylated groups, ether carboxylates are more soluble in water and less sensitive to water hardness compared to conventional soaps. Also, keeping the best properties of nonionic surfactants, they do not exhibit any cloud point and show good wetting and foam stability. Ether carboxylates do not undergo hydrolysis in the presence of alkalis or acids.

Alkyl polyglycol ether carboxylate, sodium salt (R = C₈H₁₇ −C₁₈H₃₇)

Applications.
Emulsifiers and emulsion stabilizers, in hair conditioners and in shampoos in combination with alcohol ether sulfates and possibly with cationics.

 

1.2 Sulfuric Acid Derivatives

1.2.1 Alkyl Sulfates

Alkyl sulfates are organic esters of sulfuric acid; the sulfur atom is bridged to the carbon atom of the hydrocarbon chain via an oxygen atom. Sodium lauryl sulfate (SLS), one of the most common surfactants, belongs to this class.

Sodium alkylsulfate (R_opt. = C₁₂H₂₅ −C₁₄H₂₉)

Ammonium alkylsulfate (R_opt. = C₁₂H₂₅ −C₁₄H₂₉)

Monoethanol amine alkylsulfate (R_opt. = C₁₂H₂₅ −C₁₄H₂₉)

Applications.
Alkyl sulfates have been, for about 25 years, the most important synthetic surfactant. They are foamers, emulsifiers and are still used in cosmetics and personal care areas. They are also used in combination with other surfactants to improve the foaming characteristics of detergent systems. Pure SLS is used in oral care and incorporated in dental creams.

 

1.2.2 Alkyl Ether Sulfates

Alkyl ether sulfates (AES), which are also called alcohol ethoxy sulfates (AEOS), result from the sulfation of an ethoxylated alcohol.

Sodium alkyl ether sulfate

Applications.
Alkyl ether sulfates are used as household cleaners (e.g., carpet cleaners), dishwashing liquids, and fabric care (powders and liquids), in personal care products such as liquid soaps, shower gels, foam baths, and, especially, shampoos. Increasing ethoxylation degree reduces skin and eye irritation. They are generally combined with other nonionic or anionic surfactants.

 

1.3 Sulfonic Acids and Salts

In contrast to alkyl sulfates in alkyl sulfonates the sulfur atom is directly linked to the carbon atom making the substances stable against hydrolysis.

 

1.3.1 Alkyl Sulfonates

Three major types of alkyl sulfonates must be considered: the primary and secondary paraffin sulfonates (PS and SAS) and the α-olefin sulfonates (AOS).

Primary sodium alkyl sulfonate

Secondary sodium alkyl sulfonate

Sodium alkene sulfonate

Sodium hydroxy alkane sulfonate

Applications.
Alkane sulfonates (PS and SAS) are very water soluble showing good foaming, wetting and emulsifying properties. They are mainly used in Europe in heavy- and light-duty powder detergents as well as in all-purpose hard-surface liquid cleaners. Due to their excellent resistance to high electrolyte contents, alkane sulfonates have also found interesting prospects in concentrated industrial or domestic cleaners containing mineral chemical additives.

α-Olefin sulfonates have been mainly used in Asia as surfactants for heavy- and light-duty laundry detergents, synthetic soap bars, and household products; they have also been used in the United States in several personal care products (liquid soaps, bubble baths, and shampoos) as alternatives to alcohol ether sulfates. They are also marginally used in oral care formulations.

 

1.3.2 Alkyl Aryl Sulfonates

Linear alkylbenzene sulfonates are the most important surfactants used. They are biodegradable. Linear alkylbenzene sulfonates exhibit good chemical and thermal stabilities and can be incorporated in spray-dried slurries.

Sodium linear alkylbenzene sulfonate (LAS) (R = C₉H₁₉ −C₁₅H₃₁)

Applications.
Linear alkylbenzene sulfonates are very cost-effective surfactants which are used in a broad variety of detergents for household, fabric care, institutional, and industrial products. In laundry products (powders and liquids), LAS is the surfactant of choice, usually used in combination with other anionic or non-ionic surfactants. LAS is also an appropriate anionic surfactant for light-duty and delicate powder laundry detergents. Linear alkylbenzene sulfonates are wellknown in hand dishwashing formulations, often in combination with AEOS (i.e., alcohol ethoxy sulfate), providing better foam resistance. Due to its very high detersive action, LAS has a low compatibility with skin and is scarcely used in cosmetics, except in antiseborrheic preparations.

 

1.3.3 Sulfosuccinates

Sulfosuccinates are the sodium salts of alkyl esters of sulfosuccinic acid; monoesters of sulfosuccinic acid based on linear fatty alcohols are only partially water-soluble and hardly dispersible. Those based on fatty alcohol ethoxylates exhibit much better solubility. Dialkyl esters based on alcohols with less than nine carbons, preferably five to eight carbon atoms, as well as those based on fatty acid ethanol amides are water soluble and, therefore, are generally preferred. Disodium salts of monoesters deliver good detergency and foam properties. Due to the ester linkage, all sulfosuccinates are sensitive to hydrolysis, especially under acidic conditions.

Sodium dialkyl sulfosuccinate

Sodium alkyl sulfosuccinamate

Sodium ethoxylated alkylamido sulfosuccinate

Applications.
The monoesters of alkanolamides and their derivatives are extensively used in personal care products and especially in shampoos often in combination with other anionic surfactants. The diesters are used as dispersing and wetting agents in industrial or institutional applications such as emulsion polymerization, the textile industry, ink manufacture, dry cleaning, and agriculture.

 

1.3.4 Sulfo Fatty Acid Esters

Among this group of surfactants the α-sulfo fatty acid esters are commonly used on an industrial scale. The α-sulfo fatty acid esters contain the sulfonate group statistically distributed along the carboxylate chain.

Alkyl ester of α-sulfo fatty acid sodium salt

Applications.
α-sulfo methyl ester surfactants deriving from C₁₆-C₁₈ fatty acid are used in phosphate-free laundry detergents.

 

1.3.5 Fatty Acid Isethionates and Taurides

Taurides (or taurates) are acylamino alkane sulfonates which have chemical structures close to isethionates.

Fatty acid isethionate

Tauride

Applications.
These surfactants are insensitive to water hardness and show good wetting, foaming, and emulsifying properties. In addition, they have excellent compatibility with the skin. Acyl isethionates have been used in shampoos and personal cleaners. They are also incorporated in syndet bars, together with various soaps.

 

1.4 Phosphoric Acid Esters and Salts

This class of surfactants includes alkyl phosphates and alkyl ether phosphates.

Disodium alkyl phosphoric ester

Sodium dialkyl phosphoric ester

Sodium ethoxylated alkyl phosphate

Sodium di-ethoxylated alkyl phosphate

Applications.
Phosphate esters are used in formulations where a particular tolerance to pH, heat, or electrolytes is required. They are also used in acidic cleaning products for household as well as industrial applications. They act as metal stripping or dipping agents and, thereby, increase paint adhesion. The phosphate esters also show antistatic properties to the treated substrates. Incorporated in dry cleaning compositions, phosphate ester provide, in addition to an exceptional detergency. The less water-soluble phosphate esters are also used as antifoaming agents and are applied as emulsifiers in agrochemical applications (e.g., concentrate fertilizer solutions).

 

1.5 Acylamino Acids and Salts

1.5.1 Acyl Glutamtes

Acyl glutamtes are based on α-aminoglutaric acid.

HOOC−CH2−CH2−CH(NH2)−COOH

α-aminoglutaric acid

Sodium acylglutamate

Applications.
Personal care products such as shampoos, mild to the skin and delivering improved skin feel.

 

1.5.2 Acyl Peptides

Acyl peptides are formed from hydrolyzed proteins e.g., animal collagen. The average polypeptide molecular weight can vary from about 350 to 2000.

Sodium acyl polypeptide(X = amino acids side groups)

Applications.
Acyl peptides are used in shampoos, they are prone to microbial degradation and are rather tolerant to water hardness.

 

1.5.3 Acyl Sarcosides

Sarcosinates (or salts of acyl amino acids) are the condensation products of fatty acids with N-methylglycine (CH₃-NH-CH₂-COOH) (or sarcosine).

Acylamino acid sodium salt

Applications.
Sarcosinates are mild to skin. They are also used as corrosion inhibitors.

 

2 Cationic Surfactants

2.1 Alkyl Amines

Primary, secondary, and tertiary alkyl amines and, especially, their salts are uncharged in neutral solution and therefore are not strictly cationic. They can be considered as cationics in a pH low enough to provide the ionic form; otherwise, they must be considered as nonionics. Salts of fatty amines can deliver a germicidal activity; their fungicidal efficacy is enhanced when the amine is neutralized with salicylic or o-chlorobenzoic acid.

Alkyl amine salt

Dimethyl alkyl amine salt

Alkylamido dimethyl propylamnine salt

Applications.
Amines are used in textile treatment (e.g., antistatic treatment) and occasionally in rinse fabric softeners. Amido-amines are also used in cosmetic products. Salts of stearyl and tallow fatty amines are used in some mining applications (e.g., flotation process). Fatty amines, diamines and polyamines find other prospects as adhesive agents in the coating of damp surfaces with paint or bitumen and as corrosion inhibitors.

 

2.2 Alkylimidazolines

Alkyl aminoethyl imidazoline

Alkyl hydroxyethyl imidazoline

Imidazolines are cationic O/W emulsifiers. They adsorb at metal surfaces and improve the adhesion of the applied layer to substrates.

 

2.3 Quaternary Ammonium Compounds

2.3.1 Tetraalkyl(-aryl) Ammonium Salts

The water solubility of quaternaries primarily depends on the nature of R substituents (hydrophobic chain lengths, polarity, etc.). Quaternaries carrying two or more long hydrophobic chains have very poor water solubility. Low-solubility quaternaries can adsorb on various substrates and impart various useful conditioning effects (softening, antistatic, corrosion inhibition, etc.). Quaternaries are generally not compatible with anionics because of the formation of a water-insoluble complex.

Applications.
The major use of quarternaries is related to their ability to adsorb on natural or synthetic substrates and fibers. Less-soluble long hydrophobic chain containing compounds (e.g., C₁₆-C₁₈ dialkyldimethyl ammonium chlorides) deposit on fibers. Their softening and antistatic properties are similarly exploited in hair conditioning shampoos or after-shampooing rinses. In cosmetic applications, quaternaries could cause ocular and local irritation; nevertheless, their potential for skin penetration is very low. Among the quaternaries, some are used as germicides, disinfectants, or sanitizers, they are especially effective against gram-positive but less effective against gram-negative bacteria. Quaternaries are also used as emulsifiers in acidic creams and lotions. N-Alkyltrimethyl ammonium salts are used as emulsifiers in applications requiring a selective adsorption of the emulsifier on the treated substrate.

 

2.3.2 Heterocyclic Ammonium Salts

Heterocyclic quaternaries are derived from heterocyclic aliphatic or aromatic compounds. They are often based on morpholine, imidazoline, pyridine and isoquinoline.

Alkylethyl morpholinium ethosulfate

Alkylpyridinium chloride

Dialkylmethyl imidazolinium methosulfate

Applications.
The quaternaries derived from imidazoline and morpholine are used as hair conditioners and antistatic agents. Those derived from aromatic heterocycles are used as germicides. N-Alkyl imidazoline chlorides are also used as emulsifiers in applications where the adsorption of the emulsifying agent on the substrate is desired.

 

2.4 Ethoxylated Alkyl Amines

These surfactants can be considered as cationic or nonionic, depending on the degree of ethoxylation and on the pH at which they are used. Polyethoxylated amines are formed by ethoxylation of primary or secondary fatty amines. The poloxamines are formed by the reaction of ethylene diamine with propylene oxide. Other tetrafunctional products are obtained by successive reactions of ethylene diamine with ethylene oxide and propylene oxide. lt must be noted that the above surfactants based on ethylene diamine, although intrinsically cationic, essentially behave as nonionic surfactants.

Laurylamine-POE-6

Ethoxylated diamidoamine chloride

Alkyl propanediamine ethoxylate

Ethylene diamine based POE/POP product

Applications.
The ethoxylated alkyl amines are emulsifying agents in agrochemical emulsions, wax emulsions, and two-phase emulsion cleaners. They are used as corrosion inhibitors in oil refineries. In personal care, ethoxylated alkyl amines act as emulsifiers and hair conditioning agents.

 

2.5 Esterified Quaternaries

Esterified quaternaries (or esterquats) show fabric softening properties. They are biodegradable and nonsensitizing agents which could be used in dermatology.

N-Methyl-N,N-bis-[(cetostearoyl)ethyl]-N-(2-hydroxyethyl)ammonium-methosulfate

Applications.

The esterquats are suitable substitutes for straight quaternaries with comparable softening properties.

 

3 Amphoteric Surfactants

Amphoteric surfactants show depending on the pH of the solution a positive or a negative charge. They exhibit to have a ”zwitterionic” character showing an isoelectric point.

 

3.1 Acyl Ethylenediamines and Derivatives

These surfactants show amphoteric properties and the zwitterionic form appears around neutral pH; the water solubility is minimal at the isoelectric point.

N-Hydroxyethyl-N-carboxymethyl-N’-acyl-ethylenediamne sodium salt

N-Carboxymethyl-N-carboxymethyl-oxyethyl-N’-acyl-ethylenediamine disodium salt

N-Carboxyethyl-N-carboxyethyloxyethyl-N’-acyl-ethylenediamine disodium salt

Applications.
Amphoterics of this class are similar to those of betaines. They are used in personal care products, baby shampoos, fabric softeners, industrial and car cleaners. They are compatible with other surfactants and tolerate hard water and electrolytes.

 

3.2 N-Alkyl Amino Acids or Imino Diacids

These molecules are chemical derivatives of amino acids.

Alkyl aminopropionic acid sodium salt

Sodium coco glycinate

Di-carboxyethyl-alkylamin disodium salt

Applications. 
N-Alkyl amino acids or diacid amphoterics are used in personal care household products. They are compatible with other surfactants, electrolytes and hard water. They show good emulsifying, foaming and wetting properties.

 

3.3 Alkyl Betaines

The positive charge is always carried by a quaterized nitrogen, whereas the anionic site can be a carboxylate (betaine), a sulfate or a phosphate. Betaines are good foaming, wetting, and emulsifying surfactants, especially in the presence of anionics. Detergency is best in alkaline conditions. Betaines are compatible with other surfactants and they frequently form mixed micelles; these mixtures often deliver unique properties which are not found in the individual constitutive surfactants. In their straight cationic form (i.e., in neutral and acidic conditions), betaines are not affected by water hardness ions and other metallic ions. They have hydrotropic properties, helping to solubilize ethoxylated nonionic surfactants in the presence of salting-out ions. Betaines are especially mild to skin and have the ability to improve the skin tolerance against irritating anionic surfactants.

Alkylbetaine

Alkylamidopropyl betaine

Imidazolinium betaine

Alkylamidopropyl hydroxysultaine

Alkylamidopropyl hydroxyphostaine

Applications.
Betaines have low eye and skin irritation; moreover, the presence of betaines is known to decrease the irritation effect of anionics. For the above reasons and also due to their high price, they are usually used in association with other surfactants. Betaines are thus especially suitable in personal care applications (shampoos, foam baths, liquid soaps, shower gels, etc.), fabric hand-wash products, and dish-washing products.

 

4 Nonionic Surfactants

4.1 Fatty Alcohols

Applications. Fatty alcohols are primarily used as co-emulsifiers. They are starting materials in the production of ethoxylated fatty alcohols.

 

4.2 Ethers

4.2.1 Ethoxylated Fatty Alcohols

There is a wide range of emulsifiers, wetting agents and solubilizers based on fatty alcohols available. They vary in both: the chain length of the fatty alcohol and the ethoxyl content. The influence of the fatty alcohol chain length on the properties of the compound is small compared to that of the polyoxyethylene chain.

Fatty alcohol polyglycol etherwith x = C₈ −C₁₈ and y =∼ 2 to 300

Applications.

Detergents in industrial and household products often in combination with nonionics. Ethoxylated fatty alcohols are also used in personal care products as emulsifiers and solubilizers.

 

4.2.2 Ethylene oxide/Propylene oxide-Block Polymers

These surfactants consist of a central polypropylene glycol part (PPG) representing the hydrophobic portion of the molecule and two hydrophilic polyethylene glycol chains (PEG). They are also called EO/PO block polymers. Depending on the mol weight and the proportion between PPG and PEG a wide variety of surface active agents can be produced, showing different properties.

Applications.

EO/PO block polymers are used in dishwashing and laundry detergents. They have thickening and gelling properties which makes them interesting for cosmetics. In the pharmaceutical field the more hydrophilic types are used as solubilizers under the name poloxamer.

 

4.2.3 Alkylphenol Ethoxylates

They are also called alkylphenol polyglycol ethers and belong to the most important types of washing active substances with excellent wetting properties. Due to ecotoxicological reasons their use however diminishs. The octylphenol and nonylphenol ethers are of special importance.

Octylphenol polyglycol ether

Nonylphenol polyglycol ether

Applications.

Depending on the degree of ethoxylation they may be used as wetting and washing agents as well as emulsifiers and solubilizers.

 

4.2.4 Alkylpolyglucosides

The numerous hydroxyls of glucoside groups ensure the solubility of the whole molecule in water. Alkylpolyglucosides (APGs) show good water solubility and have their cloud points at rather high temperatures (generally above 100℃); they are only slightly sensitive to the presence of electrolytes and are only very rarely influenced by water hardness. The optimal detergency of APGs is found for an average alkyl chain length around 13 and a glucosidic content of about 65 %. Alkylpolyglucosides show good chemical stability at neutral and alkaline pH. Their biodegradability is excellent.

AlkylpolyglucosideR = fatty acid

Applications.

Alkylpolyglucosides are used in detergents and personal care cleansers (e.g., shampoos); they are known to be mild for skin.

4.2.5 Ethoxylated Oils and Fats

This class of surfactants covers ethoxylated derivatives of lanolin (wool fat) and castor oil. Lanolin is the generic name of a wax containing a complex mixture of esters and polyesters of high-molecular-weight alcohols (aliphatic, steroid, and triterpenoid) and fatty acids (saturated, unsaturated, hydroxylated, and nonhydroxylated). Castor oil is the natural extract resulting from cold pressing of ricinus seeds, a mixture of a triglyceride of fatty acids (ricinoleic 87.5 %, oleic 5 %, linoleic 4 %, palmitic 1.5 %, linolenic 0.5 %, stearic 0.5 %, dihydroxystearic 0.5 % and arachidic 0.5 %).

Applications.
Ethoxylated products of lanolin and castor oil are good emulsifiers and solubilizers respectively. They are mainly used in the cosmetics industry; the ricinus based products are solubilizers for pharmaceutical purposes.

4.3 Alkanolamides

4.3.1 Alkanolamides

Alkanolamides are N-acyl derivatives of monoethanolamine and diethanolamine.

Monoalkanolamide

Dialkanolamide

Esteramide

Applications.
Alkanolamides are foamers, foam boosters and foam stabilizers. They are used in household detergent products, shampoos and cleaners.

4.3.2 Ethoxylated Alkanolamides

The reaction of an alkanolamide with ethylene oxide leads to an ethoxylated amide. Their properties are comparable to those of ethoxylated alcohols.

Polyethoxylated monoalkanolamide

Polyethoxylated dialkanolamide

Applications.
As thickening, foam stabilizing and dispersing substances. Their application in car wash is also mentioned.

 

4.4 Esters

4.4.1 Ethoxylated fatty acids

Theoretically POE could react at both ends with one fatty acid. Nevertheless the reaction of a fatty acid with ethylene oxide leads mainly to the monoester with a broad distribution in the molar EO number (n); the reaction of polyethylene glycol with fatty acids leads to a mixture of mono- and diesters besides free fatty acid.

Fatty acid monoester

Fatty acid diester

The monoesters are much more soluble in water than the diesters. These surfactants are readily hydrolyzed under acidic or alkaline conditions.

Applications.
Fatty acid POE esters are excellent emulsifiers for cosmetic, household and indurial use.

If properly balanced, combinations of esters with low and high degree of ethoxylation provide excellent emulsifier properties for creams and lotions. Therefore they have special interest in combined emulsifiers in pharmacy.

 

4.4.2 Glycol and Glycerol Esters

The esters of fatty acids and glycol or glycerol are lipopholic surfactants showing a HLB value below 10.

Ethylene glycol ester

Propylene glycol ester

Glycerol monoester(Monoglyceride)

Glycerol-1,3-diester(Diglyceride)

Applications.
Due to their very low toxicity, these surfactants are edible and, therefore, they are widely used in the food industry, especially in applications involving W/O emulsions or dispersions (e.g., butter, diet butter, margarine, etc.). Glycol and glycerol esters are also used in pharmaceutical and cosmetic industry either as emulsifying agents or as oily compounds in creams, lotions, ointments, gels.

 

4.4.3 Sorbitan Esters

Sorbitol can form two different sorbitans by internal dehydration: the 1,4- and the 1,5-sorbitan. Further dehydration of the 1,4-sorbitan leads to iso-sorbide. In common sorbitan based surfactants the 1,4-sorbitan is dominating. Fatty acid esters of sorbitan are insoluble in water, their HLB value is below 10.

Chemical structure of the basic compounds

Sorbitol

1,4-sorbitan

1,5-sorbitan

iso-sorbide

Chemical structure of sorbitan based emulsifiers

1,4-Sorbitan monoester

1,4-Sorbitan triester

Applications.
Emulsifiers often in combination with ethoxylated sorbitanesters of fatty acids.

 

4.4.4 Alkyl Carbohydrate Esters

Alkyl carbohydrate esters are also known under the names ”sugar esters” and”sucrose esters”. Normally they ar based on saccharose. Mono- and diesters are produced. The mono esters are water soluble while the dieseters are not. Due to the steric effects, primary hydroxyl groups are almost exclusively subject to esterification. They are of great interest due to their natural origin of their components and good biodegradability.

Saccharose fatty acid monoester

Saccharose fatty acid diester

Applications.
Sucrose esters are food-grade ingredients and have similar food additive usages as the previously described glycol, glycerol, and sorbitan esters.

 

4.5 Ester/Ether Surfactants

These surfactants contain besides the ester group, which is formed by a fatty acid and a polyol as described in the previous section, ether linkages normally originating from polyoxyethylene. In general they are more hydrophilic compared to the ester surfactants and exhibit HLB values above 10.

 

4.5.1 Ethoxylated Glycol and Glyerol Esters

Ethoxylated glycol monoester

Ethoxylated glycerol monoester

Besides the monoesters diesters are possible mainly in the case of glycerol.

Applications.
Emulsifiers for O/W emulsions in cosmetic and pharmacy.

 

4.5.2 Ethoxylated Sorbitan Esters

Ethoxylation of sorbitan fatty acid esters leads to an important surfactant class for pharmacy and cosmetics. The fatty acids used are: lauric, myristic, palmitic, stearic and oleic acid.

Ethoxylated 1,4-sorbitan monooleate (as an example) w + x + y + z≅20

Applications.
Emulsifiers for cosmetic and pharmaceutical emulsions, solubilizers for oily liquids like vitamins and hormones. Wetting agents in suspensions.

 

4.5.3 Ethoxylated Pentaerythritol Esters

Ethoxylated pentaerythritol monoleate

Applications.
Emulsifier for cosmetic preparations.

 

4.5.4 Polyglycerol monoester

This is the only class of ether bounds containing emulsifiers which do not contain polyoxyethylene groups. The ether linkage is formed from glycerol units.

Polyglycerol monoleate

 

4.6 Amine Oxides

Amine oxides are produced from alkyl dimethyl amine, where the alkyl chain is a C₁₂-C₁₈ unit by oxidation. The methyl groups could be partially replaced by other functional groups like amidopropyl, hydroxyethyl or hydroxypropyl.

Alkyl dimethylamine oxide

Applications.
Incorporated in shampoos, amine oxides contribute to impart viscosity, reduce eye irritancy, and enhance foam properties. They are especially suitable in slightly acidic or neutral formulas. In domestic cleaners the amine oxides are used in association with anionics. Industrial applications are: liquid bleach products, textile industry, foam stabilizers and anti corrosion formulations.

 

5 Alkoxylated Polysiloxanes

Alkoxylated polysiloxanes are derived from polydimethyl siloxane, where methyl groups are substituted by hydrophilic groups which can be anionic, cationic or nonionic.

 

A denotes a hydrophilic group like polyoxyethylene, amines etc.

Silicone surfactants show excellent wetting capacity on low-energy surfaces. Also, their diluted solutions can considerably decrease the surface tension to below 20 mN/m. Foam is easily controlled; foaming efficacy is depressed along with decreasing ethylene oxide/propylene oxide ratio. Ethoxylated polydimethylsiloxanes are rather inert and exhibit excellent chemical stability.

Applications.
These surfactants are used as additives in paints, foam controlling agents, textile auxiliaries, wetting agents and in cosmetic preparations like protectic creams, body milks, shampoos and conditioners.

The CFTA adopted name for these surfactants is Dimethicone copolyol.

 

6 Fluorosurfactants

Fluorosurfactants contain perfluoroalkyls chains F-(CF₂-CF₂)-, in which n ranges from about 3 to about 8. They are excellent wetting agents showing a critical surface tension of about 25mN/m. Similar to conventional surfactants, a rather broad variety of hydrophilic functions (ethoxylated chains, sulfonates, quaternaries, betaines, etc.) can be born by fluorosurfactants. These hydrophilic groups are generally not directly grafted on the fluorocarbon chain and are linked through a short intermediate hydrocarbon chain. Depending on their nature, these surfactants show variable emulsifying and foaming characteristics. They have excellent thermal and chemical stability; therefore, they find prospects in those extreme conditions in which the hydrocarbon surfactants would decompose. The major drawback of fluorosurfactants is that they are not environment friendly because they are resistant to biodegradation.

 

Applications.
Although they have some potential prospects in personal care (improved hair conditioning) and household, fluorosurfactants find their major applications in industrial areas like water based adhesives, wetting agents, flotation processes and battery technology.

Comparison of the Properties of Various Surfactant Types[1]

Properties	Amphoteric	Anionic	Nonionic	Cationic
Foaming	good	good	moderate to weak	moderate to good
Wetting	weak	good to very good	good	weak
Emulsification	good	good	good to very good	weak
Compatibility with
Electrolytes	very good	weak to good	weak	weak
Acids	very good	weak	weak	good
Bases	very good	weak	weak	weak
Hardness Constituents of Water	very good	good	moderate to weak	moderate to weak
Other Surfactant Types	compatible with cationics	incompatible with cationics	compatible with all types	incompatible with anionics
Detergency	good	good	good	weak
Irritation of Skin and/or Mucosa	weak	weak to strong	weak to strong	weak to strong
Hydrotropic Effect	very good	weak to good	not present	not present
Biodegradable	yes	not all types	not all types	not all types
Lime soap dispersing	very good	good	very good	not compatible
Synergistic Effect[a]	very good with nonionics, anionics and cationics	not generally	good to very good with anionics and amphoterics	not present
Compatibility with soap foam	very good	defoaming action	defoaming action	incompatible
[a] Refers to the ability to show enhanced properties in the presence of other surfactants.

 

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^[1] Individual representatives of the surfactant groups show deviating properties.