EUROPEAN PHARMACOPOEIA 11.
2 Polysorbate 20
n1 = volume of 0.01 M sodium thiosulfate required for
the substance to be examined, in millilitres ;
n2 = volume of 0.01 M sodium thiosulfate required for
the blank titration, in millilitres ;
M = molarity of the sodium thiosulfate solution, in
moles per litre ;
E. (2R)-2-[4-[2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo-
[2,3-d]pyrimidin-5-yl)ethyl]benzamido]pentanedioic acid. m = mass of the substance to be examined, in grams.
Saponification value (2.5.6) : 40 to 50, determined on 4.0 g.
Use 15.0 mL of 0.5 M alcoholic potassium hydroxide and dilute
with 50 mL of ethanol (96 per cent) R before carrying out the
07/2023:0426 titration. Heat under reflux for 60 min.
Composition of fatty acids (2.4.22, Method C). Prepare
reference solution (a) as indicated in Table 2.4.22.-2.
Column :
– material : fused silica ;
POLYSORBATE 20 – size : l = 30 m, Ø = 0.32 mm ;
– stationary phase : macrogol 20 000 R (film thickness 0.5 μm).
Polysorbatum 20 Carrier gas : helium for chromatography R.
Linear velocity : 50 cm/s.
DEFINITION
Temperature :
Mixture of partial esters of fatty acids, mainly lauric
Time Temperature
(dodecanoic) acid, with sorbitol and its anhydrides ethoxylated
(min) (°C)
with approximately 20 moles of ethylene oxide for each mole
Column 0 - 14 80 → 220
of sorbitol and sorbitol anhydrides.
14 - 54 220
CHARACTERS
Injection port 250
Appearance : oily, yellow or brownish-yellow, clear or slightly
opalescent liquid. Detector 250
Solubility : soluble in water, in anhydrous ethanol, in ethyl Detection : flame ionisation.
acetate and in methanol, practically insoluble in fatty oils and
Injection : 1 μL.
in liquid paraffin.
Composition of the fatty-acid fraction of the substance :
Relative density : about 1.10.
– caproic acid : maximum 1.0 per cent ;
Viscosity : about 400 mPa·s at 25 °C. – caprylic acid : maximum 10.0 per cent ;
IDENTIFICATION – capric acid : maximum 10.0 per cent ;
– lauric acid : 40.0 per cent to 60.0 per cent ;
First identification : A, D.
– myristic acid : 14.0 per cent to 25.0 per cent ;
Second identification : B, C, D, E.
– palmitic acid : 7.0 per cent to 15.0 per cent ;
A. Infrared absorption spectrophotometry (2.2.24). – stearic acid : maximum 7.0 per cent ;
Comparison : Ph. Eur. reference spectrum of polysorbate 20. – oleic acid : maximum 11.0 per cent ;
B. Hydroxyl value (see Tests). – linoleic acid : maximum 3.0 per cent.
C. Saponification value (see Tests). Ethylene oxide and dioxan (2.4.25, Method A): maximum
D. Composition of fatty acids (see Tests). 1 ppm of ethylene oxide and 10 ppm of dioxan.
E. Dissolve 0.1 g in 5 mL of methylene chloride R. Add 0.1 g of Water (2.5.12) : maximum 3.0 per cent, determined on 1.00 g.
potassium thiocyanate R and 0.1 g of cobalt nitrate R. Stir Total ash (2.4.16) : maximum 0.25 per cent, determined on
with a glass rod. The solution becomes blue. 2.0 g.
TESTS STORAGE
Acid value (2.5.1) : maximum 2.0. In an airtight container, protected from light.
FUNCTIONALITY-RELATED CHARACTERISTICS
Dissolve 5.0 g in 50 mL of the prescribed solvent mixture.
This section provides information on characteristics that are
Hydroxyl value (2.5.3, Method A) : 96 to 108. recognised as being relevant control parameters for one or
Peroxide value : maximum 10.0. more functions of the substance when used as an excipient
(see chapter 5.15). Some of the characteristics described in
Introduce 10.0 g into a 100 mL beaker and dissolve with 20 mL
the Functionality-related characteristics section may also be
of glacial acetic acid R. Add 1 mL of saturated potassium iodide present in the mandatory part of the monograph since they
solution R, mix and allow to stand for 1 min. Add 50 mL of also represent mandatory quality criteria. In such cases, a
carbon dioxide-free water R and a magnetic stirring bar. Titrate
cross-reference to the tests described in the mandatory part is
with 0.01 M sodium thiosulfate, determining the end-point included in the Functionality-related characteristics section.
potentiometrically (2.2.20). Carry out a blank titration. If the Control of the characteristics can contribute to the quality
result of the blank determination exceeds 0.1 mL of titration
of a medicinal product by improving the consistency of the
reagent, replace the reagents and repeat the determination. manufacturing process and the performance of the medicinal
Determine the peroxide value using the following expression : product during use. Where control methods are cited, they are
recognised as being suitable for the purpose, but other methods
( n1 - n2 ) ´ M ´ 1000 can also be used. Wherever results for a particular characteristic
m are reported, the control method must be indicated.
General Notices (1) apply to all monographs and other texts 4925
Polysorbate 40 EUROPEAN PHARMACOPOEIA 11.2
The following characteristics may be relevant for polysorbate 20 n1 = volume of 0.01 M sodium thiosulfate required for
used as emulsifier or solubiliser in liquid dosage forms and in the substance to be examined, in millilitres ;
semi-solid preparations. n2 = volume of 0.01 M sodium thiosulfate required for
Hydroxyl value (see Tests). the blank titration, in millilitres ;
Composition of fatty acids (see Tests). M = molarity of the sodium thiosulfate solution, in
moles per litre ;
m = mass of the substance to be examined, in grams.
Saponification value (2.5.6) : 41 to 52, determined on 4.0 g.
07/2023:1914 Use 15.0 mL of 0.5 M alcoholic potassium hydroxide and dilute
with 50 mL of ethanol (96 per cent) R before carrying out the
titration. Heat under reflux for 60 min.
Composition of fatty acids (2.4.22, Method C). Prepare
reference solution (a) as indicated in Table 2.4.22.-1.
POLYSORBATE 40 Column :
– material : fused silica ;
Polysorbatum 40 – size : l = 30 m, Ø = 0.32 mm ;
– stationary phase : macrogol 20 000 R (film thickness 0.5 μm).
DEFINITION
Carrier gas : helium for chromatography R.
Mixture of partial esters of fatty acids, mainly Palmitic
acid (1904), with sorbitol and its anhydrides ethoxylated with Linear velocity : 50 cm/s.
approximately 20 moles of ethylene oxide for each mole of Temperature :
sorbitol and sorbitol anhydrides.
Time Temperature
(min) (°C)
CHARACTERS 0 - 14 80 → 220
Column
Appearance : oily, viscous, yellowish or brownish-yellow liquid.
14 - 54 220
Solubility : miscible with water, with anhydrous ethanol, with
Injection port 250
ethyl acetate and with methanol, practically insoluble in fatty
oils and in liquid paraffin. Detector 250
Relative density : about 1.10.
Detection : flame ionisation.
Viscosity : about 400 mPa·s at 30 °C.
Injection : 1 μL.
IDENTIFICATION Composition of the fatty-acid fraction of the substance :
First identification : A, D. – palmitic acid : minimum 92.0 per cent.
Second identification : B, C, D, E. Ethylene oxide and dioxan (2.4.25, Method A): maximum
1 ppm of ethylene oxide and maximum 10 ppm of dioxan.
A. Infrared absorption spectrophotometry (2.2.24).
Water (2.5.12) : maximum 3.0 per cent, determined on 1.00 g.
Comparison : Ph. Eur. reference spectrum of polysorbate 40.
Total ash (2.4.16) : maximum 0.25 per cent, determined on
B. Hydroxyl value (see Tests). 2.0 g.
C. Saponification value (see Tests).
STORAGE
D. Composition of fatty acids (see Tests).
In an airtight container, protected from light.
E. Dissolve 0.1 g in 5 mL of methylene chloride R. Add 0.1 g of
potassium thiocyanate R and 0.1 g of cobalt nitrate R. Stir FUNCTIONALITY-RELATED CHARACTERISTICS
with a glass rod. The solution becomes blue. This section provides information on characteristics that are
recognised as being relevant control parameters for one or
TESTS more functions of the substance when used as an excipient
(see chapter 5.15). Some of the characteristics described in
Acid value (2.5.1) : maximum 2.0. the Functionality-related characteristics section may also be
Dissolve 5.0 g in 50 mL of the prescribed solvent mixture. present in the mandatory part of the monograph since they
also represent mandatory quality criteria. In such cases, a
Hydroxyl value (2.5.3, Method A) : 89 to 105. cross-reference to the tests described in the mandatory part is
Peroxide value : maximum 10.0. included in the Functionality-related characteristics section.
Control of the characteristics can contribute to the quality
Introduce 10.0 g into a 100 mL beaker and dissolve with 20 mL
of a medicinal product by improving the consistency of the
of glacial acetic acid R. Add 1 mL of saturated potassium iodide
manufacturing process and the performance of the medicinal
solution R, mix and allow to stand for 1 min. Add 50 mL of
product during use. Where control methods are cited, they are
carbon dioxide-free water R and a magnetic stirring bar. Titrate
recognised as being suitable for the purpose, but other methods
with 0.01 M sodium thiosulfate, determining the end-point
can also be used. Wherever results for a particular characteristic
potentiometrically (2.2.20). Carry out a blank titration. If the
are reported, the control method must be indicated.
result of the blank determination exceeds 0.1 mL of titration
reagent, replace the reagents and repeat the determination. The following characteristics may be relevant for polysorbate 40
used as emulsifier or solubiliser in liquid dosage forms and in
Determine the peroxide value using the following expression : semi-solid preparations.
( n1 - n2 ) ´ M ´ 1000 Hydroxyl value (see Tests).
m Composition of fatty acids (see Tests).
4926 See the information section on general monographs (cover pages)
