EUROPEAN PHARMACOPOEIA 10.

0 Sodium stearyl fumarate

Test solution. Place 50.0 mg of the substance to be examined Relative retention with reference to methyl stearate (retention
in a polytetrafluoroethylene digestion flask and add 0.5 mL time = about 40 min) : methyl palmitate = about 0.88.
of a mixture of 1 volume of heavy metal-free hydrochloric System suitability : reference solution :
acid R and 5 volumes of heavy metal-free nitric acid R. Allow
to digest at 170 °C for 5 h. Allow to cool. Dissolve the residue – resolution : minimum 5.0 between the peaks due to methyl
in water R and dilute to 5.0 mL with the same solvent. palmitate and methyl stearate.
Reference solutions. Prepare the reference solutions using Calculate the content of stearic acid and palmitic acid.
nickel standard solution (10 ppm Ni) R, diluting as necessary
STORAGE
with water R.
Source : nickel hollow-cathode lamp. In an airtight container, protected from light.
Wavelength : 232.0 nm.
Atomisation device : furnace.
Loss on drying (2.2.32) : maximum 5.0 per cent. 07/2010:1567
corrected 10.0
In a weighing glass introduce 1.0 g of previously washed
sand R, dry at 105 °C and weigh. Add 0.500 g of the substance
to be examined and 10 mL of ethanol (96 per cent) R. Evaporate
at 80 °C and dry the residue at 105 °C for 4 h.
Microbial contamination
SODIUM STEARYL FUMARATE
TAMC : acceptance criterion 103 CFU/g (2.6.12).
TYMC : acceptance criterion 102 CFU/g (2.6.12). Natrii stearylis fumaras
Absence of Escherichia coli (2.6.13).
Absence of Salmonella (2.6.13).
ASSAY
Sodium. Dissolve 0.250 g with gentle heating in a mixture of C22H39NaO4 Mr 390.5
5 mL of acetic anhydride R and 20 mL of anhydrous acetic [4070-80-8]
acid R. Cool and add 20 mL of dioxan R. Titrate with 0.1 M
perchloric acid, determining the end-point potentiometrically DEFINITION
(2.2.20).
Sodium octadecyl (E)-butenedioate.
1 mL of 0.1 M perchloric acid is equivalent to 2.299 mg of Na.
Content : 99.0 per cent to 101.5 per cent (anhydrous substance).
Stearic acid and palmitic acid. Gas chromatography (2.2.28) :
use the normalisation procedure. CHARACTERS
Test solution. In a conical flask fitted with a reflux condenser, Appearance : white or almost white, fine powder with
dissolve 0.10 g of the substance to be examined in 5 mL of agglomerates of flat, circular particles.
boron trifluoride-methanol solution R. Boil under a reflux Solubility : practically insoluble in water, slightly soluble in
condenser for 10 min. Add 4 mL of heptane R through methanol, practically insoluble in acetone and in anhydrous
the condenser and boil again under a reflux condenser for ethanol.
10 min. Allow to cool. Add 20 mL of saturated sodium
chloride solution R. Shake and allow the layers to separate. IDENTIFICATION
Remove about 2 mL of the organic layer and dry over 0.2 g
of anhydrous sodium sulfate R. Dilute 1.0 mL of the solution Infrared absorption spectrophotometry (2.2.24).
to 100.0 mL with heptane R. Comparison : sodium stearyl fumarate CRS.
Reference solution. Prepare the reference solution in the same TESTS
manner as the test solution using 50.0 mg of palmitic acid CRS
and 50.0 mg of stearic acid CRS instead of the substance to Related substances. Gas chromatography (2.2.28): use the
be examined. normalisation procedure.
Column : Silylation solution. To 2 mL of N,O-bis(trimethylsilyl)trifluor-
oacetamide R add 0.02 mL of chlorotrimethylsilane R and mix.
– material : fused silica ;
Test solution. Introduce 15.0 mg of the substance to be
– size : l = 30 m, Ø = 0.32 mm ;
examined in a vial with a screw cap and add 1 mL of the
– stationary phase : macrogol 20 000 R (film thickness 0.5 μm). silylation solution. Seal the vial and heat at about 70 °C for
Carrier gas : helium for chromatography R. 1 h. After the reaction a precipitate remains in the vial ; filter
Flow rate : 2.4 mL/min. the solution through a nylon filter (pore size 0.45 μm).
Temperature : Reference solution. Introduce 1.0 mg of sodium stearyl
maleate CRS and 1.0 mg of sodium stearyl fumarate CRS into
Time Temperature a vial with a screw cap and add 1 mL of the silylation solution.
(min) (°C) Seal the vial and heat at about 70 °C for 1 h.
Column 0-2 70 Column :
2 - 36 70 → 240 – material : fused silica ;
36 - 41 240 – size : l = 15 m, Ø = 0.53 mm ;
Injection port 220 – stationary phase : methylpolysiloxane R (film thickness
0.15 μm).
Detector 260
Carrier gas : helium for chromatography R.
Detection : flame ionisation. Flow rate : 2 mL/min.
Injection : 1 μL. Split ratio : 1:25.

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General Notices (1) apply to all monographs and other texts 3845
Sodium sulfate, anhydrous EUROPEAN PHARMACOPOEIA 10.0

Temperature : DEFINITION
Time Temperature Anhydrous disodium sulfate.
(min) (°C) Content : 98.5 per cent to 101.0 per cent (dried substance).
0-1 180
CHARACTERS
Column 1 - 21 180 → 320
Appearance : white or almost white powder, hygroscopic.
21 - 26 320 Solubility : freely soluble in water.
Injection port 250
IDENTIFICATION
Detector 320 A. It gives reaction (a) of sulfates (2.3.1).
Detection : flame ionisation. B. It gives reaction (a) of sodium (2.3.1).
Injection : 2 μL. C. Loss on drying (see Tests).
Relative retention with reference to stearyl trimethylsilyl TESTS
fumarate (retention time = about 9 min) : stearyl alcohol = 0.30 ;
Solution S. Dissolve 2.2 g in carbon dioxide-free water R
stearyl trimethylsilyl ether = 0.35 ; palmityl trimethylsilyl
prepared from distilled water R and dilute to 100 mL with the
fumarate = 0.80 ; heptadecyl trimethylsilyl fumarate = 0.85 ;
same solvent.
stearyl trimethylsilyl maleate = 0.90 ; nonadecyl trimethylsilyl
fumarate = 1.05 ; eicos-11-enyl trimethylsilyl fumarate = 1.15 ; Appearance of solution. Solution S is clear (2.2.1) and
distearyl fumarate = 2.25. colourless (2.2.2, Method II).
System suitability : Acidity or alkalinity. To 10 mL of solution S add 0.1 mL
– resolution : minimum 1.5 between the peaks in the of bromothymol blue solution R1. Not more than 0.5 mL
chromatogram obtained with the reference solution. of 0.01 M hydrochloric acid or 0.01 M sodium hydroxide is
Limits : required to change the colour of the indicator.
– any impurity : maximum 0.5 per cent ; Chlorides (2.4.4) : maximum 450 ppm.
– total : maximum 5.0 per cent. Dilute 5 mL of solution S to 15 mL with water R.
Water (2.5.12) : maximum 5.0 per cent, determined on 0.250 g. Calcium (2.4.3) : maximum 450 ppm, if intended for use in
the manufacture of parenteral preparations.
ASSAY Dilute 10 mL of solution S to 15 mL with distilled water R.
Dissolve 0.250 g, accurately weighed, in 10 mL of methylene Iron (2.4.9) : maximum 90 ppm, if intended for use in the
chloride R and add 30 mL of anhydrous acetic acid R. Titrate manufacture of parenteral preparations.
with 0.1 M perchloric acid, determining the end-point
potentiometrically (2.2.20). Dilute 5 mL of solution S to 10 mL with water R.
1 mL of 0.1 M perchloric acid is equivalent to 39.05 mg of Magnesium : maximum 200 ppm, if intended for use in the
C22H39NaO4. manufacture of parenteral preparations.
To 10 mL of solution S add 1 mL of glycerol (85 per cent) R,
FUNCTIONALITY-RELATED CHARACTERISTICS 0.15 mL of titan yellow solution R, 0.25 mL of ammonium
This section provides information on characteristics that are oxalate solution R and 5 mL of dilute sodium hydroxide
recognised as being relevant control parameters for one or solution R and shake. Any pink colour in the test solution
more functions of the substance when used as an excipient is not more intense than that in a standard prepared at the
(see chapter 5.15). Some of the characteristics described in same time in the same manner using a mixture of 5 mL of
the Functionality-related characteristics section may also be magnesium standard solution (10 ppm Mg) R and 5 mL of
present in the mandatory part of the monograph since they water R.
also represent mandatory quality criteria. In such cases, a Loss on drying (2.2.32) : maximum 0.5 per cent, determined
cross-reference to the tests described in the mandatory part is on 1.000 g by drying in an oven at 130 °C.
included in the Functionality-related characteristics section.
Control of the characteristics can contribute to the quality ASSAY
of a medicinal product by improving the consistency of the Pack 20 g of strongly acidic ion-exchange resin R into a glass
manufacturing process and the performance of the medicinal column, at least 20 cm long and 20 mm in internal diameter,
product during use. Where control methods are cited, they are and cover it with water R. After 5 min, wash the resin with
recognised as being suitable for the purpose, but other methods water R until the pH of the eluate is about 6 to 7 using a pH
can also be used. Wherever results for a particular characteristic
indicator strip R. Keep the resin covered with water R. Dissolve
are reported, the control method must be indicated. 0.500 g of the substance to be examined in 10 mL of water R in
The following characteristics may be relevant for sodium stearyla beaker. Load the solution onto the column and pass through
fumarate used as a lubricant in tablets and capsules. the resin at a flow rate of about 4 mL/min until the resin is just
Particle-size distribution (2.9.31). covered with the solution. Using about 200 mL of water R,
rinse the beaker and pass the rinsings through the column
Specific surface area (2.9.26, Method I).
at the same flow rate. Check that the pH of the last eluate is
about 6 to 7 using a pH indicator strip R.
01/2019:0099 Titrate the eluate with 1 M sodium hydroxide, determining the
end-point potentiometrically (2.2.20).
1 mL of 1 M sodium hydroxide is equivalent to 71.00 mg of
Na2SO4.
SODIUM SULFATE, ANHYDROUS STORAGE
Store in an airtight container.
Natrii sulfas anhydricus
LABELLING
Na2SO4 Mr 142.0 The label states, where applicable, that the substance is suitable
[7757-82-6] for use in the manufacture of parenteral preparations.

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