EUROPEAN PHARMACOPOEIA 10.

6 Magnesium stearate

01/2022:0042 Iron (2.4.9) : maximum 400 ppm.

Dissolve 0.1 g in 3 mL of dilute hydrochloric acid R and dilute
to 10 mL with water R. Dilute 2.5 mL of this solution to 10 mL
with water R.

MAGNESIUM CARBONATE, LIGHT ASSAY

Dissolve 0.150 g in a mixture of 2 mL of dilute hydrochloric
Magnesii subcarbonas levis acid R and 20 mL of water R. Carry out the complexometric
titration of magnesium (2.5.11).
DEFINITION 1 mL of 0.1 M sodium edetate is equivalent to 4.030 mg
Hydrated basic magnesium carbonate. of MgO.
Content : 40.0 per cent to 45.0 per cent, calculated as MgO
FUNCTIONALITY-RELATED CHARACTERISTICS
(Mr 40.30).
This section provides information on characteristics that are
CHARACTERS recognised as being relevant control parameters for one or
Appearance : white or almost white powder. more functions of the substance when used as an excipient
Solubility : practically insoluble in water. It dissolves in dilute (see chapter 5.15). Some of the characteristics described in
acids with effervescence. the Functionality-related characteristics section may also be
present in the mandatory part of the monograph since they
IDENTIFICATION also represent mandatory quality criteria. In such cases, a
A. Bulk density (2.9.34): maximum 0.15 g/mL. cross-reference to the tests described in the mandatory part is
B. It gives the reaction of carbonates (2.3.1). included in the Functionality-related characteristics section.
Control of the characteristics can contribute to the quality
C. Dissolve about 15 mg in 2 mL of dilute nitric acid R and of a medicinal product by improving the consistency of the
neutralise with dilute sodium hydroxide solution R. The manufacturing process and the performance of the medicinal
solution gives the reaction of magnesium (2.3.1). product during use. Where control methods are cited, they are
TESTS recognised as being suitable for the purpose, but other methods
can also be used. Wherever results for a particular characteristic
Solution S. Dissolve 5.0 g in 100 mL of dilute acetic acid R. are reported, the control method must be indicated.
When the effervescence has ceased, boil for 2 min, allow to
cool and dilute to 100 mL with dilute acetic acid R. Filter, if The following characteristics may be relevant for light
necessary, through a previously ignited and tared porcelain or magnesium carbonate used as filler in oral solid dosage forms.
silica filter crucible of suitable porosity to give a clear filtrate. Particle-size distribution (2.9.31 or 2.9.38).
Keep the residue for the test for substances insoluble in acetic Bulk and tapped density (2.9.34).
acid.
Appearance of solution. Solution S is not more intensely 01/2022:0229
coloured than reference solution B4 (2.2.2, Method II).
Soluble substances : maximum 1.0 per cent.
Mix 2.00 g with 100 mL of water R and boil for 5 min. Filter
whilst hot through a sintered-glass filter (40) (2.1.2), allow
to cool and dilute to 100 mL with water R. Evaporate 50 mL MAGNESIUM STEARATE(1)
of the filtrate to dryness and dry at 100-105 °C. The residue
weighs a maximum of 10 mg. Magnesii stearas
Substances insoluble in acetic acid : maximum 0.05 per cent.
DEFINITION
Any residue obtained during the preparation of solution S,
washed, dried and ignited at 600 ± 50 °C, weighs a maximum Compound of magnesium with a mixture of solid organic
of 2.5 mg. acids and consisting mainly of variable proportions of
magnesium stearate and magnesium palmitate obtained from
Chlorides (2.4.4): maximum 700 ppm. sources of vegetable or animal origin.
Dilute 1.5 mL of solution S to 15 mL with water R. Content :
Sulfates (2.4.13) : maximum 0.3 per cent. – magnesium (Mg ; Ar 24.305) : 4.0 per cent to 5.0 per cent
Dilute 1 mL of solution S to 15 mL with distilled water R. (dried substance) ;
Elemental impurities. Any method that fulfils the – stearic acid in the fatty acid fraction : minimum 40.0 per
requirements of general chapter 2.4.20. Determination of cent ;
elemental impurities may be used. – sum of stearic acid and palmitic acid in the fatty acid
fraction : minimum 90.0 per cent.
Element Maximum content (ppm)
♦CHARACTERS
Arsenic 1
Appearance : white or almost white, very fine, light powder,
Cobalt 1 greasy to the touch.
Solubility : practically insoluble in water and in anhydrous
Nickel 50 ethanol.♦
Vanadium 5 IDENTIFICATION
First identification : C, D.
 

◊Second identification : A, B, D.
Calcium (2.4.3) : maximum 0.75 per cent. A. Freezing point (2.2.18) : minimum 53 °C, determined on
Dilute 2.6 mL of solution S to 150 mL with distilled water R. the residue obtained in the preparation of solution S (see
15 mL of the solution complies with the test. Tests).
(1) This monograph has undergone pharmacopoeial harmonisation. See chapter 5.8. Pharmacopoeial harmonisation.

General Notices (1) apply to all monographs and other texts 6177
Magnesium stearate EUROPEAN PHARMACOPOEIA 10.6

B. Acid value (2.5.1) : 195 to 210. bomb according to the manufacturer’s operating instructions
Dissolve 0.200 g of the residue obtained in the preparation (when using a digestion bomb, be thoroughly familiar with the
of solution S in 25 mL of the prescribed mixture of safety and operating instructions. Carefully follow the bomb
solvents.◊ manufacturer’s instructions regarding care and maintenance
C. Examine the chromatograms obtained in the assay of of these digestion bombs. Do not use metal jacketed bombs
stearic acid and palmitic acid. or liners which have been used with hydrochloric acid due
to contamination from corrosion of the metal jacket by
Results : the 2 principal peaks in the chromatogram hydrochloric acid). Heat the bomb in an oven at 170 °C for 3 h.
obtained with the test solution are similar in retention time Cool the bomb slowly in air to room temperature according
to the 2 principal peaks in the chromatogram obtained to the bomb manufacturer’s instructions. Place the bomb in a
with the reference solution. fume cupboard and open carefully as corrosive gases may be
D. To 1 mL of solution S add 1 mL of dilute ammonia R1 ; expelled. Dissolve the residue in water R and dilute to 10.0 mL
a white precipitate is formed that dissolves on addition with the same solvent.
of 1 mL of ammonium chloride solution R. Add 1 mL Reference solution. Prepare a solution of 0.0030 μg/mL of Cd
of a 120 g/L solution of disodium hydrogen phosphate by suitable dilutions of a 0.00825 μg/mL solution of cadmium
dodecahydrate R ; a white crystalline precipitate is formed. nitrate tetrahydrate R in the blank solution.
TESTS Dilute 1.0 mL of the test solution to 10.0 mL with the blank
solution. Prepare mixtures of this solution, the reference
Solution S. To 5.0 g add 50 mL of peroxide-free ether R, 20 mL
solution and the blank solution in the following proportions :
of dilute nitric acid R and 20 mL of water R and heat under a
(1.0:0:1.0 V/V/V), (1.0:0.5:0.5 V/V/V), (1.0:1.0:0 V/V/V). To
reflux condenser until dissolution is complete. Allow to cool.
each mixture add 50 μL of modifier solution and mix. These
In a separating funnel, separate the aqueous layer and shake
solutions contain respectively 0 μg, 0.00075 μg and 0.0015 μg
the ether layer with 2 quantities, each of 4 mL, of water R.
of cadmium per millilitre from the reference solution (keep the
Combine the aqueous layers, wash with 15 mL of peroxide-free
remaining test solution for use in the test for lead and nickel).
ether R and dilute to 50.0 mL with water R (solution S).
Evaporate the organic layer to dryness and dry the residue at Source : cadmium hollow-cathode lamp.
100-105 °C. Keep the residue for identification tests A and B. Wavelength : 228.8 nm.
Acidity or alkalinity. To 1.0 g add 20 mL of carbon Atomisation device : furnace.
dioxide-free water R and boil for 1 min with continuous Platform : pyrolytically coated with integrated tube.
shaking. Cool and filter. To 10 mL of the filtrate add 0.05 mL Operating conditions : use the temperature programme
of bromothymol blue solution R4. Not more than 0.05 mL of recommended for cadmium by the GFAA spectrometer
0.1 M hydrochloric acid or 0.1 M sodium hydroxide is required manufacturer. An example of temperature parameters for
to change the colour of the indicator. GFAA analysis of cadmium is shown below.
Chlorides : maximum 0.1 per cent.
Stage Final temperature Ramp time Hold time
Dilute 10.0 mL of solution S to 40 mL with water R. Neutralise (°C) (s) (s)
if necessary with nitric acid R using litmus R as indicator. Drying 110 10 20
Add 1 mL of nitric acid R and 1 mL of 0.1 M silver nitrate
and dilute to 50 mL with water R. Mix and allow to stand for Ashing 600 10 30
5 min protected from light. The turbidity, if any, is not greater Atomisation 1800 0 5
than that produced in a solution containing 1.4 mL of 0.02 M
hydrochloric acid. Lead : maximum 10 ppm.
Sulfates : maximum 1.0 per cent. Atomic absorption spectrometry (2.2.23, Method II).
Dilute 6.0 mL of solution S to 40 mL with water R. Neutralise For the preparation of all aqueous solutions and for the rinsing
if necessary with hydrochloric acid R using litmus R as of glassware before use, employ water that has been passed
indicator. Add 1 mL of 3 M hydrochloric acid R and 3 mL of a through a strong-acid, strong-base, mixed-bed ion-exchange
120 g/L solution of barium chloride R and dilute to 50 mL with resin before use. Select all reagents to have as low a content of
water R. Mix and allow to stand for 10 min. The turbidity, if cadmium, lead and nickel as practicable and store all reagent
any, is not greater than that produced in a solution containing solutions in containers of borosilicate glass. Clean glassware
3.0 mL of 0.02 M sulfuric acid. before use by soaking in a warm 773 g/L solution of nitric
Cadmium : maximum 3 ppm. acid R for 30 min and by rinsing with deionised water.
Atomic absorption spectrometry (2.2.23, Method II). Blank solution. Use the solution described in the test for
For the preparation of all aqueous solutions and for the rinsing cadmium.
of glassware before use, employ water that has been passed Modifier solution. Use the solution described in the test for
through a strong-acid, strong-base, mixed-bed ion-exchange cadmium.
resin before use. Select all reagents to have as low a content of Test solution. Use the solution described in the test for
cadmium, lead and nickel as practicable and store all reagent cadmium.
solutions in containers of borosilicate glass. Clean glassware Reference solution. Prepare a solution of 0.100 μg/mL of Pb by
before use by soaking in a warm 773 g/L solution of nitric suitable dilutions of lead standard solution (100 ppm Pb) R
acid R for 30 min and by rinsing with deionised water. with the blank solution.
Blank solution. Dilute 25 mL of cadmium- and lead-free nitric Prepare mixtures of the test solution, the reference solution
acid R to 100.0 mL with water R. and the blank solution in the following proportions :
Modifier solution. Dissolve 20 g of ammonium dihydrogen (1.0:0:1.0 V/V/V), (1.0:0.5:0.5 V/V/V), (1.0:1.0:0 V/V/V). To
phosphate R and 1 g of magnesium nitrate R in water R and each mixture add 50 μL of modifier solution and mix. These
dilute to 100 mL with the same solvent. Alternatively, use solutions contain respectively 0 μg, 0.025 μg and 0.05 μg of
an appropriate matrix modifier as recommended by the lead per millilitre from the reference solution.
graphite furnace atomic absorption (GFAA) spectrometer
Source : lead hollow-cathode lamp.
manufacturer.
Wavelength : 283.3 nm.
Test solution. Place 0.100 g of the substance to be examined
in a polytetrafluoroethylene digestion bomb and add 2.5 mL Atomisation device : furnace.
of cadmium- and lead-free nitric acid R. Close and seal the Platform : pyrolytically coated with integrated tube.

6178 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 10.6 Magnesium stearate

Operating conditions : use the temperature programme of 0.1 M sodium edetate and 15 mg of mordant black 11
recommended for lead by the GFAA spectrometer triturate R. Heat at 45-50 °C until the solution is clear and
manufacturer. An example of temperature parameters for titrate with 0.1 M zinc sulfate until the colour changes from
GFAA analysis of lead is shown below. blue to violet. Carry out a blank titration.
Stage Final temperature Ramp time Hold time 1 mL of 0.1 M sodium edetate is equivalent to 2.431 mg of Mg.
(°C) (s) (s) Stearic acid and palmitic acid. Gas chromatography (2.2.28) :
Drying 110 10 20 use the normalisation procedure.
Ashing 450 10 30 Test solution. In a conical flask fitted with a reflux condenser,
dissolve 0.10 g of the substance to be examined in 5 mL of
Atomisation 2000 0 5 boron trifluoride-methanol solution R. Boil under a reflux
condenser for 10 min. Add 4 mL of heptane R through
Nickel : maximum 5 ppm. the condenser and boil again under a reflux condenser for
Atomic absorption spectrometry (2.2.23, Method II). 10 min. Allow to cool. Add 20 mL of saturated sodium
For the preparation of all aqueous solutions and for the rinsing chloride solution R. Shake and allow the layers to separate.
of glassware before use, employ water that has been passed Dry the organic layer over 0.1 g of anhydrous sodium sulfate R
through a strong-acid, strong-base, mixed-bed ion-exchange (previously washed with heptane R). Dilute 1.0 mL of the
resin before use. Select all reagents to have as low a content of solution to 10.0 mL with heptane R.
cadmium, lead and nickel as practicable and store all reagent Reference solution. Prepare the reference solution in the same
solutions in containers of borosilicate glass. Clean glassware manner as the test solution using 50.0 mg of palmitic acid CRS
before use by soaking in a warm 773 g/L solution of nitric and 50.0 mg of stearic acid CRS instead of the substance to
acid R for 30 min and by rinsing with deionised water. be examined.
Blank solution. Use the solution described in the test for Column :
cadmium. – material : fused silica ;
Modifier solution. Dissolve 20 g of ammonium dihydrogen – size : l = 30 m, Ø = 0.32 mm ;
phosphate R in water R and dilute to 100 mL with the same – stationary phase : macrogol 20 000 R (film thickness 0.5 μm).
solvent. Alternatively, use an appropriate matrix modifier as
Carrier gas : helium for chromatography R.
recommended by the GFAA spectrometer manufacturer.
Flow rate : 2.4 mL/min.
Test solution. Use the solution described in the test for
cadmium. Temperature :
Reference solution. Prepare a solution of 0.050 μg/mL of Ni by Time Temperature
suitable dilutions of a 0.2477 μg/mL solution of nickel nitrate (min) (°C)
hexahydrate R in the blank solution. Column 0-2 70
Prepare mixtures of the test solution, the reference solution 2 - 36 70 → 240
and the blank solution in the following proportions :
(1.0:0:1.0 V/V/V), (1.0:0.5:0.5 V/V/V), (1.0:1.0:0 V/V/V). To 36 - 41 240
each mixture add 50 μL of matrix modifier solution and mix. Injection port 220
These reference solutions contain respectively 0 μg, 0.0125 μg
and 0.025 μg of nickel per millilitre from the reference Detector 260
solution.
Detection : flame ionisation.
Source : nickel hollow-cathode lamp. Injection : 1 μL.
Wavelength : 232.0 nm. Relative retention with reference to methyl stearate : methyl
Atomisation device : furnace. palmitate = about 0.9.
Platform : pyrolytically coated with integrated tube. System suitability : reference solution :
Operating conditions : use the temperature programme – resolution : minimum 5.0 between the peaks due to methyl
recommended for nickel by the GFAA spectrometer palmitate and methyl stearate ;
manufacturer. An example of temperature parameters for – relative standard deviation : maximum 3.0 per cent for the
GFAA analysis of nickel is shown below. areas of the peaks due to methyl palmitate and methyl
Stage Final temperature Ramp time Hold time stearate, determined on 6 injections ; maximum 1.0 per
(°C) (s) (s) cent for the ratio of the areas of the peaks due to methyl
Drying 110 10 20 palmitate to the areas of the peaks due to methyl stearate,
determined on 6 injections.
Ashing 1000 20 30
◊FUNCTIONALITY-RELATED CHARACTERISTICS
Atomisation 2300 0 5
This section provides information on characteristics that are
Loss on drying (2.2.32) : maximum 6.0 per cent, determined recognised as being relevant control parameters for one or
on 1.000 g by drying in an oven at 105 °C. more functions of the substance when used as an excipient
(see chapter 5.15). Some of the characteristics described in
♦Microbial contamination the Functionality-related characteristics section may also be
TAMC : acceptance criterion 103 CFU/g (2.6.12). present in the mandatory part of the monograph since they
TYMC : acceptance criterion 102 CFU/g (2.6.12). also represent mandatory quality criteria. In such cases, a
cross-reference to the tests described in the mandatory part is
Absence of Escherichia coli (2.6.13). included in the Functionality-related characteristics section.
Absence of Salmonella (2.6.13).♦ Control of the characteristics can contribute to the quality
of a medicinal product by improving the consistency of the
ASSAY manufacturing process and the performance of the medicinal
Magnesium. To 0.500 g in a 250 mL conical flask add product during use. Where control methods are cited, they are
50 mL of a mixture of equal volumes of anhydrous ethanol R recognised as being suitable for the purpose, but other methods
and butanol R, 5 mL of concentrated ammonia R, 3 mL of can also be used. Wherever results for a particular characteristic
ammonium chloride buffer solution pH 10.0 R, 30.0 mL are reported, the control method must be indicated.

General Notices (1) apply to all monographs and other texts 6179
Methyl parahydroxybenzoate EUROPEAN PHARMACOPOEIA 10.6

The following characteristics may be relevant for magnesium Results : the principal spot in the chromatogram obtained
stearate used as lubricant in tablets and capsules. with test solution (b) is similar in position and size to
Particle-size distribution (2.9.31). the principal spot in the chromatogram obtained with
reference solution (a).◊
Specific surface area (2.9.26, Method I). Determine the
specific surface area in the P/Po range of 0.05 to 0.15. TESTS
Sample outgassing : 2 h at 40 °C. Solution S. Dissolve 1.0 g in ethanol (96 per cent) R and dilute
Thermogravimetry (2.2.34).◊ to 10 mL with the same solvent.
Appearance of solution. Solution S is clear (2.2.1) and not
more intensely coloured than reference solution BY6 (2.2.2,
01/2022:0409 Method II).
Acidity. To 2 mL of solution S add 3 mL of ethanol (96 per
cent) R, 5 mL of carbon dioxide-free water R and 0.1 mL of
bromocresol green solution R. Not more than 0.1 mL of 0.1 M
sodium hydroxide is required to change the colour of the
METHYL PARAHYDROXYBENZOATE(2) indicator to blue.
Related substances. Liquid chromatography (2.2.29).
Methylis parahydroxybenzoas Test solution. Dissolve 50.0 mg of the substance to be
examined in 2.5 mL of methanol R and dilute to 50.0 mL with
the mobile phase. Dilute 10.0 mL of this solution to 100.0 mL
with the mobile phase.
Reference solution (a). Dissolve 5 mg of 4-hydroxybenzoic
acid R (impurity A) and 5 mg of the substance to be examined
C 8H 8O 3 Mr 152.1 in the mobile phase and dilute to 100.0 mL with the mobile
[99-76-3] phase. Dilute 1.0 mL of this solution to 10.0 mL with the
mobile phase.
DEFINITION Reference solution (b). Dissolve 50.0 mg of methyl
Methyl 4-hydroxybenzoate. parahydroxybenzoate CRS in 2.5 mL of methanol R and dilute
Content : 98.0 per cent to 102.0 per cent. to 50.0 mL with the mobile phase. Dilute 10.0 mL of this
solution to 100.0 mL with the mobile phase.
♦CHARACTERS Reference solution (c). Dilute 1.0 mL of the test solution to
Appearance : white or almost white, crystalline powder or 20.0 mL with the mobile phase. Dilute 1.0 mL of this solution
colourless crystals. to 10.0 mL with the mobile phase.
Solubility : very slightly soluble in water, freely soluble in Column :
ethanol (96 per cent) and in methanol.♦ – size : l = 0.15 m, Ø = 4.6 mm ;
– stationary phase : end-capped octadecylsilyl silica gel for
IDENTIFICATION chromatography R (5 μm).
First identification : A, B. Mobile phase : 6.8 g/L solution of potassium dihydrogen
◊Second identification : A, C.◊ phosphate R, methanol R (35:65 V/V).
A. Melting point (2.2.14) : 125 °C to 128 °C. Flow rate : 1.3 mL/min.
B. Infrared absorption spectrophotometry (2.2.24). Detection : spectrophotometer at 272 nm.
Comparison : methyl parahydroxybenzoate CRS. Injection : 10 μL of the test solution and reference solutions (a)
◊C. Thin-layer chromatography (2.2.27). and (c).
Test solution (a). Dissolve 0.10 g of the substance to be Run time : 5 times the retention time of methyl
examined in acetone R and dilute to 10 mL with the same parahydroxybenzoate.
solvent. Relative retention with reference to methyl
Test solution (b). Dilute 1 mL of test solution (a) to 10 mL parahydroxybenzoate (retention time = about 2.3 min) :
with acetone R. impurity A = about 0.6.
Reference solution (a). Dissolve 10 mg of methyl System suitability : reference solution (a) :
parahydroxybenzoate CRS in acetone R and dilute to 10 mL – resolution : minimum 2.0 between the peaks due to
with the same solvent. impurity A and methyl parahydroxybenzoate.
Reference solution (b). Dissolve 10 mg of ethyl Limits :
parahydroxybenzoate CRS in 1 mL of test solution (a) and – correction factor : for the calculation of content, multiply
dilute to 10 mL with acetone R. the peak area of impurity A by 1.4 ;
Plate : TLC octadecylsilyl silica gel F254 plate R. – impurity A : not more than the area of the principal peak
Mobile phase : glacial acetic acid R, water R, methanol R in the chromatogram obtained with reference solution (c)
(1:30:70 V/V/V). (0.5 per cent);
Application : 2 μL of test solution (b) and reference – unspecified impurities : for each impurity, not more than the
solutions (a) and (b). area of the principal peak in the chromatogram obtained
Development : over 2/3 of the plate. with reference solution (c) (0.5 per cent) ;
– total : not more than twice the area of the principal peak
Drying : in air.
in the chromatogram obtained with reference solution (c)
Detection : examine in ultraviolet light at 254 nm. (1.0 per cent);
System suitability : reference solution (b): – disregard limit : 0.2 times the area of the principal peak in
– the chromatogram shows 2 clearly separated principal the chromatogram obtained with reference solution (c)
spots. (0.1 per cent).
(2) This monograph has undergone pharmacopoeial harmonisation. See chapter 5.8. Pharmacopoeial harmonisation.

6180 See the information section on general monographs (cover pages)