Fiedler - Encyclopedia of Excipients

Fiedler - Encyclopedia of Excipients

“Fiedler – Encyclopedia of Excipients” is a comprehensive database on excipients used in pharmacy, cosmetics and related fields offering 12,000+ entries. Monographs follow a uniform structure:

  • Names and synonyms: INN, INCI, compendial, trivial and chemical names, trademarks, CAS-, EINECS- and E-numbers
  • Definition: Description, composition, chemical structure, molar mass
  • Basic properties: Appearance, physicochemical data, solubility, spectra, etc.
  • Application characteristics and main uses in pharmacy and cosmetics, illustrated by examples
  • Stability and incompatibilities
  • Pharmacology and toxicology
  • Analysis methods
  • References with broad literature citations
  • List of excipient suppliers

A manufacturers directory gives addresses and full contact details.

Substances, and manufacturers are possible search entries. Several filter options are available. All substances are linked to their manufacturers.
Substances, and manufacturers are possible search entries. Several filter options are available. All substances are linked to their manufacturers.

Updates

Regular updates

Fiedler - Encyclopedia of Excipients

Manual

Preface

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

Abbreviations

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

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

Units of Measurements

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 Vn=…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

TΘtϑ

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

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, 5th ed., vol. 2 Methods, p. 586-587, Springer, Berlin, Heidelberg, New York (1991).

EU-Declaration of Excipients

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.

Cosmetic Ingredient Review (CIR)

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

Toxicity Profiles

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

Residual Solvents

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

Limits for Drinking Water

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

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 17th Street, NW, Suite 300, Washington, D.C. 20036-4702, USA; Principles of cosmetic licensing in Japan, 2nd 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

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

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

Surfactants

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 (Ropt. = C12H25 −C14H29)

Ammonium alkylsulfate (Ropt. = C12H25 −C14H29)

Monoethanol amine alkylsulfate (Ropt. = 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.

 


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

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