Sorbitan Esters (Sorbitan Fatty Acid Esters)

20

General References

21

Radus TP, Gyr G. Determination of antimicrobial preservatives in

pharmaceutical formulations using reverse-phase liquid chromatography. J Pharm Sci 1983; 72: 221224.
Sofos JN, Busta FF. Sorbates. Branen AL, Davidson PM, eds. Antimicrobials
in Foods. New York: Marcel Dekker, 1983; 141175.
Warth A. Mechanism of resistance of Saccharomyces bailii to benzoic, sorbic
and other weak acids used as food preservatives. J Appl Bacteriol 1977;
43: 215230.

67 5

Authors

W Cook, ME Quinn, PJ Sheskey.

22 Date of Revision
7 January 2009.

Sorbitan Esters (Sorbitan Fatty Acid Esters)

1
BP:

Nonproprietary Names
Sorbitan Laurate
Sorbitan Oleate
Sorbitan Palmitate
Sorbitan Stearate
Sorbitan Trioleate
JP:
Sorbitan Sesquioleate
PhEur: Sorbitan Laurate
Sorbitan Oleate
Sorbitan Palmitate
Sorbitan Sesquioleate
Sorbitan Stearate
Sorbitan Trioleate
USP-NF: Sorbitan Monolaurate (sorbitan, esters monodecanoate)
Sorbitan Monooleate
Sorbitan Monopalmitate
Sorbitan Monostearate
Sorbitan Sesquioleate
Sorbitan Trioleate
2
Synonyms
See Table I.
3
Chemical Names and CAS Registry Numbers
See Table II.
4
Empirical Formula and Molecular Weight
See Table III.
Table III: Empirical formula and molecular weight of selected sorbitan
esters.
Name

Formula

Molecular weight

Sorbitan diisostearate
Sorbitan dioleate
Sorbitan monoisostearate
Sorbitan monolaurate
Sorbitan monooleate
Sorbitan monopalmitate
Sorbitan monostearate
Sorbitan sesquiisostearate
Sorbitan sesquioleate
Sorbitan sesquistearate
Sorbitan triisostearate
Sorbitan trioleate
Sorbitan tristearate

C42H80O7
C42H76O7
C24H46O6
C18H34O6
C24H44O6
C22H42O6
C24H46O6
C33H63O6.5
C33H60O6.5
C33H63O6.5
C60H114O8
C60H108O8
C60H114O8

697
693
431
346
429
403
431
564
561
564
964
958
964

Structural Formula

R1 = R2 = OH, R3 = R (see below) for sorbitan monoesters

R1 = OH, R2 = R3 = R for sorbitan diesters
R1 = R2 = R3 = R for sorbitan triesters
where R = (C17H35)COO for isostearate (C11H23)COO for
laurate
(C17H33)COO for oleate
(C15H31)COO for palmitate
(C17H35)COO for stearate
The sesquiesters are equimolar mixtures of monoesters and diesters.
6
Functional Category
Dispersing agent; emulsifying agent; nonionic surfactant; solubilizing agent; suspending agent; wetting agent.
7

Applications in Pharmaceutical Formulation or

Technology
Sorbitan monoesters are a series of mixtures of partial esters of
sorbitol and its mono- and dianhydrides with fatty acids. Sorbitan
diesters are a series of mixtures of partial esters of sorbitol and its
monoanhydride with fatty acids.
Sorbitan esters are widely used in cosmetics, food products, and
pharmaceutical formulations as lipophilic nonionic surfactants.
They are mainly used in pharmaceutical formulations as emulsifying agents in the preparation of creams, emulsions, and ointments
for topical application. When used alone, sorbitan esters produce
stable water-in-oil emulsions and microemulsions, but are frequently used in combination with varying proportions of a
polysorbate to produce water-in-oil or oil-in-water emulsions or
creams of varying consistencies, and also in self-emulsifying drug
delivery systems for poorly soluble compounds.(1)
Sorbitan monolaurate, sorbitan monopalmitate and sorbitan
trioleate have also been used at concentrations of 0.010.05% w/v

6 76

Sorbitan Esters (Sorbitan Fatty Acid Esters)

Table I: Synonyms of selected sorbitan esters.

Name

Synonym

Sorbitan monoisostearate
Sorbitan monolaurate

1,4-Anhydro-D-glucitol, 6-isooctadecanoate; anhydrosorbitol monoisostearate; Arlacel 987; Crill 6; sorbitan isostearate.

Arlacel 20; Armotan ML; Crill 1; Dehymuls SML; E493; Glycomul L; Hodag SML; Liposorb L; Montane 20; ProtachemSML;
Sorbester P12; Sorbirol L; sorbitan laurate; sorbitani lauras; Span 20; Tego SML.
Ablunol S-80; Arlacel 80; Armotan MO; Capmul O; Crill 4; Crill 50; Dehymuls SMO; Drewmulse SMO; Drewsorb 80K; E494;
Glycomul O; Hodag SMO; Lamesorb SMO; Liposorb O; Montane 80; Nikkol SO-10; Nissan Nonion OP-80R; Norfox Sorbo
S-80; Polycon S80 K; Proto-sorb SMO; Protachem SMO; S-Maz 80K; Sorbester P17; Sorbirol O; sorbitan oleate; sorbitani
oleas; Sorgen 40; Sorgon S-40-H; Span 80; Tego SMO.
1,4-Anhydro-D-glucitol, 6-hexadecanoate; Ablunol S-40; Arlacel 40; Armotan MP; Crill 2; Dehymuls SMP; E495; Glycomul P;
Hodag SMP; Lamesorb SMP; Liposorb P; Montane 40; Nikkol SP-10; Nissan Nonion PP-40R; Protachem SMP; Proto-sorb
SMP; Sorbester P16; Sorbirol P; sorbitan palmitate; sorbitani palmitas; Span 40.
Ablunol S-60; Alkamuls SMS; 1,4-Anhydro-D-glucitol, 6-octadecanoate; anhydrosorbitol monostearate; Arlacel 60; Armotan
MS; Atlas 110K; Capmul S; Crill 3; Dehymuls SMS; Drewmulse SMS; Drewsorb 60K; Durtan 6O; Durtan 60K; E491;
Famodan MS Kosher; Glycomul S FG; Glycomul S KFG; Hodag SMS; Lamesorb SMS; Liposorb S; Liposorb SC; Liposorb S-K;
Montane 60; Nissan Nonion SP-60R; Norfox Sorbo S-60FG; Polycon S60K; Protachem SMS; Prote-sorb SMS; S-Maz 60K; SMaz 60KHS; Sorbester P18; Sorbirol S; sorbitan stearate; sorbitani stearas; Sorgen 50; Span 60; Span 60K; Span 60 VS;
Tego SMS.
Protachem SQI.
Arlacel C; Arlacel 83; Crill 43; Glycomul SOC; Hodag SSO; Liposorb SQO; Montane 83; Nikkol SO-15; Nissan Nonion OP83RAT; Protachem SOC; sorbitani sesquioleas; Sorgen 30; Sorgen S-30-H.
Span 25.
Ablunol S-85; Arlacel 85; Crill 45; Glycomul TO; Hodag STO; Liposorb TO; Montane 85; Nissan Nonion OP-85R; Protachem
STO; Prote- sorb STO; S-Maz 85K; Sorbester P37; sorbitani trioleas; Span 85; Tego STO.
Alkamuls STS; Crill 35; Crill 41; Drewsorb 65K; E492; Famodan TS Kosher; Glycomul TS KFG; Hodag STS; Lamesorb STS;
Liposorb TS; Liposorb TS-K; Montane 65; Protachem STS; Proteo-sorb STS; Sorbester P38; Span 65; Span 65K.

Sorbitan monooleate

Sorbitan monopalmitate
Sorbitan monostearate

Sorbitan sesquiisostearate
Sorbitan sesquioleate
Sorbitan trilaurate
Sorbitan trioleate
Sorbitan tristearate

Table II: Chemical name and CAS Registry Number of selected sorbitan
esters.
Name

Chemical name

CAS number

Sorbitan diisostearate

Sorbitan
diisooctadecanoate
(Z,Z)-Sorbitan di-9octadecanoate
Sorbitan monododecanoate
Sorbitan
monoisooctadecanoate
(Z)-Sorbitan mono-9octadecenoate
Sorbitan
monohexadecanoate
Sorbitan monooctadecanoate
Sorbitan
sesquiisooctadecanoate
(Z)-Sorbitan sesqui-9octadecenoate
Sorbitan sesquioctadecanoate
Sorbitan
triisooctadecanoate
(Z,Z,Z)-Sorbitan tri-9octadecenoate
Sorbitan tri-octadecanoate

[68238-87-9]

Sorbitan dioleate
Sorbitan monolaurate
Sorbitan monoisostearate
Sorbitan monooleate
Sorbitan monopalmitate
Sorbitan monostearate

Sorbitan sesquiisostearate
Sorbitan sesquioleate
Sorbitan sesquistearate
Sorbitan triisostearate
Sorbitan trioleate
Sorbitan tristearate

[29116-98-1]
[1338-39-2]
[71902-01-7]

Emulsifying agent
Used alone in water-in-oil emulsions
Used in combination with hydrophilic emulsifiers in
oil-in-water emulsions
Used to increase the water-holding properties of
ointments
Solubilizing agent
For poorly soluble, active constituents in lipophilic
bases
Wetting agent
For insoluble, active constituents in lipophilic bases

Name

Appearance

Sorbitan monoisostearate
Sorbitan monolaurate
Sorbitan monooleate
Sorbitan monopalmitate
Sorbitan monostearate
Sorbitan sesquioleate
Sorbitan trioleate
Sorbitan tristearate

Yellow viscous liquid

Yellow viscous liquid
Yellow viscous liquid
Cream solid
Cream solid
Amber viscous liquid
Amber viscous liquid
Cream/yellow solid

[1338-43-8]
[26266-57-9]
[1338-41-6]
[71812-38-9]
[8007-43-0]
[51938-44-4]

in the preparation of an emulsion for intramuscular administration.

See Table IV.
8
Description
Sorbitan esters occur as cream- to amber-colored liquids or solids
with a distinctive odor and taste; see Table V.

[54392-27-7]
[26266-58-0]
[26658-19-5]

Table IV: Uses of sorbitan esters.

Use

Table V: Appearance of selected sorbitan esters.

Concentration (%)
115
110
110
110
0.13

9
Pharmacopeial Specifications
See Table VI.
10 Typical Properties
Acid value see Table VII.
Density see Table VII.
Flash point >1498C
HLB value see Table VII.
Hydroxyl value see Table VII.
Iodine number see Table VII.
Melting point see Table VII.
Moisture content see Table VIII.
NIR spectra see Figure 1.
Pour point see Table VII.
Saponification value see Table VIII.
Solubility Sorbitan esters are generally soluble or dispersible in
oils; they are also soluble in most organic solvents. In water,
although insoluble, they are generally dispersible.

Sorbitan Esters (Sorbitan Fatty Acid Esters)

Table VI table continues

JP XV

PhEur 6.0

USP32NF27

Test

Identification
Characters
Acidity
Acid value
Sorbitan monolaurate
Sorbitan monooleate
Sorbitan
monopalmitate
Sorbitan
monostearate
Sorbitan sesquioleate
Sorbitan trioleate
Hydroxyl value
Sorbitan monolaurate
Sorbitan monooleate
Sorbitan
monopalmitate
Sorbitan
monostearate
Sorbitan sesquioleate
Sorbitan trioleate
Iodine value
Sobitan monolaurate
Sorbitan monooleate
Sorbitan sesquioleate
Sorbitan trioleate
Peroxide value
Sorbitan monolaurate
Sorbitan monooleate
Sorbitan
monopalmitate
Sorbitan
monostearate
Sorbitan sesquioleate
Sorbitan trioleate
Saponification value
Sorbitan monolaurate
Sorbitan monooleate
Sorbitan
monopalmitate
Sorbitan
monostearate
Sorbitan sesquioleate
Sorbitan trioleate
Water
Sorbitan monolaurate
Sorbitan monooleate
Sorbitan
monopalmitate
Sorbitan
monostearate
Sorbitan sesquioleate
Sorbitan trioleate
Residue on ignition
Sorbitan monolaurate
Sorbitan monooleate
Sorbitan
monopalmitate
Sorbitan
monostearate
Sorbitan sesquioleate
Sorbitan trioleate
Total ash
Heavy metals
Arsenic
Specific gravity
Sorbitan monolaurate
Sorbitan monooleate
Sorbitan sesquioleate
Sorbitan trioleate

47.0
48.0
48.0

48
48
48

410.0

410

416.0
416.0

414
417

330358
190210
270305

330358
190215
275305

235260

235260

180215
5575

182220
5075

Melting point
Sorbitan palmitate
Sorbitan
monostearate
Assay for fatty acids
Sorbitan monolaurate
Sorbitan monooleate
Sorbitan
monopalmitate
Sorbitan
monostearate
Sorbitan sesquioleate
Sorbitan trioleate
Assay for polyols
Sorbitan monolaurate
Sorbitan monooleate
Sorbitan
monopalmitate
Sorbitan
monostearate
Sorbitan sesquioleate
Sorbitan trioleate

410.0
6276
7095
7690

6276
6575
7785

45.0
410.0
45.0

45.0

410.0
410.0

1000 [2nd deriv. log(1/R)]

Test

JP XV

PhEur 6.0

USP32NF27

44518C
50608C

55.063.0%
72.078.0%
63.071.0%

68.076.0%

74.080.0%
85.590.0%

39.045.0%
25.031.0%
32.038.0%

27.034.0%

22.028.0%
13.019.0%

1.6

1.0

1748
1678
1236

1780

2326

1404

0.0

log(1/R)

Table VI: Pharmacopeial specifications for sorbitan esters.

67 7

1392
2351
1764

2312

158170
145160
140155

158170
145160
140150

147157

147157

150168

145166
170190

143165
169183

41.5%
41.5%
41.5%

41.5%
41.0%
41.5%

41.5%

41.5%

43.0%

41.5%
41.5%

41.0%
40.7%

40.5%
40.5%
40.5%

40.5%

12

41.0%

420 ppm
42 ppm

40.5%
410 ppm

41.4%
40.25%

40.001%

13 Method of Manufacture
Sorbitol is dehydrated to form a hexitan (1,4-sorbitan), which is
then esterified with the desired fatty acid.

0.9601.020

!0.98
!0.99
!0.99
!0.98

table continues

1215
1731

2.5
0.1
1100 1300 1500 1700 1900 2100 2300 2500

Wavelength/nm
Figure 1: Near-infrared spectrum of sorbitan esters (sorbitan fatty acid
esters) measured by reflectance.

Surface tension see Table VIII.

Viscosity (dynamic) see Table VIII.
11 Stability and Storage Conditions
Gradual soap formation occurs with strong acids or bases; sorbitan
esters are stable in weak acids or bases.
Sorbitan esters should be stored in a well-closed container in a
cool, dry place.
Incompatibilities

14 Safety
Sorbitan esters are widely used in cosmetics, food products, and oral
and topical pharmaceutical formulations, and are generally
regarded as nontoxic and nonirritant materials. However, there
have been occasional reports of hypersensitive skin reactions
following the topical application of products containing sorbitan

6 78

Sorbitan Esters (Sorbitan Fatty Acid Esters)

Table VII: Typical properties of selected sorbitan esters.

Name

Acid value

Density (g/cm3)

HLB value

Hydroxyl value

Iodine number

Melting point
(8C)

Pour point (8C)

Sorbitan monoisostearate
Sorbitan monolaurate
Sorbitan monooleate
Sorbitan monopalmitate
Sorbitan monostearate
Sorbitan sesquioleate
Sorbitan trioleate
Sorbitan tristearate

48
47
48
37
510
8.513
1014
47

1.01
1.01
1.0

1.0
0.95

4.7
8.6
4.3
6.7
4.7
3.7
1.8
2.1

220250
159169
193209
270303
235260
188210
5570
6080

47

41
41

4348
5357

1620
"12

Table VIII: Typical properties of selected sorbitan esters.

Name

Saponification value

Surface tension of 1% aqueous solution (mN/m)

Viscosity at 258C (mPa s)

Water content (%)

Sorbitan monoisostearate
Sorbitan monolaurate
Sorbitan monooleate
Sorbitan monopalmitate
Sorbitan monostearate
Sorbitan sesquioleate
Sorbitan trioleate
Sorbitan tristearate

143153
159169
149160
142152
147157
149160
170190
172185

28
30
36
46

32
48

39004900
9701080
Solid
Solid
1500
200250
Solid

41.0
40.5
40.5
41.0
41.0
41.0
41.0
41.0

esters.(25) When heated to decomposition, the sorbitan esters emit

acrid smoke and irritating fumes.
The WHO has set an estimated acceptable daily intake of
sorbitan monopalmitate, monostearate, and tristearate,(6) and of
sorbitan monolaurate and monooleate(7) at up to 25 mg/kg bodyweight calculated as total sorbitan esters.
Sorbitan monolaurate
LD50 (rat, oral): 33.6 g/kg.(8)
Experimental neoplastigen.
Sorbitan monostearate
LD50 (rat, oral): 31 g/kg.(8)
Very mildly toxic by ingestion. Experimental reproductive
effects.

15 Handling Precautions
Observe normal precautions appropriate to the circumstances and
quantity of material handled. Eye protection and gloves are
recommended.
16 Regulatory Status
Certain sorbitan esters are accepted as food additives in the UK.
Sorbitan esters are included in the FDA Inactive Ingredients
Database (inhalations; IM injections; ophthalmic, oral, topical,
and vaginal preparations). Sorbitan esters are used in nonparenteral
medicines licensed in the UK. Sorbitan esters are included in the
Canadian List of Acceptable Non-medicinal Ingredients.
17 Related Substances
Polyoxyethylene sorbitan fatty acid esters.
18 Comments
EINECS numbers
Sorbitan diisostearate 269-410-7
Sorbitan dioleate 249-448-0
Sorbitan laurate 215-663-3
Sorbitan oleate 215-665-4
Sorbitan palmitate 247-568-8
Sorbitan sesquiolate 232-360-1
Sorbitan sesquistearate 257-529-7
Sorbitan stearate 215-664-9

Sorbitan triisostearate 259-141-3

Sorbitan trioleate 247-569-3
Sorbitan tristearate 247-891-4
19

Specific References

1 Fatouros DG et al. Clinical studies with oral lipid based formulations of

poorly soluble compounds. Clin Risk Manag 2007; 3: 591604.
2 Finn OA, Forsyth A. Contact dermatitis due to sorbitan monolaurate.
Contact Dermatitis 1975; 1: 318.
3 Hannuksela M et al. Allergy to ingredients of vehicles. Contact
Dermatitis 1976; 2: 105110.
4 Austad J. Allergic contact dermatitis to sorbitan monooleate (Span 80).
Contact Dermatitis 1982; 8: 426427.
5 Boyle J, Kennedy CTC. Contact urticaria and dermatitis to Alphaderm.
Contact Dermatitis 1984; 10: 178.
6 FAO/WHO. Toxicological evaluations of certain food additives with a
review of general principles and of specifications. Seventeenth report of
the joint FAO/WHO expert committee on food additives. World Health
Organ Tech Rep Ser 1974; No. 539.
7 FAO/WHO. Evaluation of certain food additives and contaminants.
Twenty-sixth report of the joint FAO/WHO expert committee on food
additives. World Health Organ Tech Rep Ser 1982; No. 683.
8 Lewis RJ, ed. Saxs Dangerous Properties of Industrial Materials, 11th
edn. New York: Wiley, 2004; 3291.

20

General References

Konno K et al. Solubility, critical aggregating or micellar concentration and

aggregate formation of non-ionic surfactants in non-aqueous solutions.
J Colloid Interface Sci 1974; 49: 383.
Mittal KL, ed. Micellization, Solubilization and Microemulsions. New York:
Plenum Press, 1977.
Smolinske SC. Handbook of Food, Drug, and Cosmetic Excipients. Boca
Raton, FL: CRC Press, 1992; 369370.
Suzuki E et al. Studies on methods of particle size reduction of medicinal
compounds VIII: size reduction by freeze-drying and the influence of
pharmaceutical adjuvants on the micromeritic properties of freeze-dried
powders. Chem Pharm Bull 1979; 27: 12141222.
Whitworth CW, Pongpaibul Y. The influence of some additives on the
stability of aspirin in an oleaginous suppository base. Can J Pharm Sci
1979; 14: 3638.

21 Author
D Zhang.
22 Date of Revision
28 January 2009.