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EUROPEAN PHARMACOPOEIA 10.

0 Magnesium stearate

01/2015:0229 Chlorides : maximum 0.1 per cent.


corrected 10.0 Dilute 10.0 mL of solution S to 40 mL with water R. Neutralise
if necessary with nitric acid R using litmus R as indicator.
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
5 min protected from light. The turbidity, if any, is not greater
MAGNESIUM STEARATE(1) than that produced in a solution containing 1.4 mL of 0.02 M
hydrochloric acid.
Magnesii stearas Sulfates : maximum 1.0 per cent.
DEFINITION Dilute 6.0 mL of solution S to 40 mL with water R. Neutralise
if necessary with hydrochloric acid R using litmus R as
Compound of magnesium with a mixture of solid organic
indicator. Add 1 mL of 3 M hydrochloric acid R and 3 mL of a
acids and consisting mainly of variable proportions of
120 g/L solution of barium chloride R and dilute to 50 mL with
magnesium stearate and magnesium palmitate obtained from
water R. Mix and allow to stand for 10 min. The turbidity, if
sources of vegetable or animal origin.
any, is not greater than that produced in a solution containing
Content : 3.0 mL of 0.02 M sulfuric acid.
– magnesium (Mg ; Ar 24.305): 4.0 per cent to 5.0 per cent Cadmium : maximum 3 ppm.
(dried substance) ;
– stearic acid in the fatty acid fraction : minimum 40.0 per Atomic absorption spectrometry (2.2.23, Method II).
cent ; For the preparation of all aqueous solutions and for the rinsing
– sum of stearic acid and palmitic acid in the fatty acid of glassware before use, employ water that has been passed
fraction : minimum 90.0 per cent. through a strong-acid, strong-base, mixed-bed ion-exchange
resin before use. Select all reagents to have as low a content of
♦CHARACTERS cadmium, lead and nickel as practicable and store all reagent
Appearance : white or almost white, very fine, light powder, solutions in containers of borosilicate glass. Clean glassware
greasy to the touch. before use by soaking in a warm 773 g/L solution of nitric
acid R for 30 min and by rinsing with deionised water.
Solubility : practically insoluble in water and in anhydrous
ethanol.♦ Blank solution. Dilute 25 mL of cadmium- and lead-free nitric
acid R to 100.0 mL with water R.
IDENTIFICATION
Modifier solution. Dissolve 20 g of ammonium dihydrogen
First identification : C, D. phosphate R and 1 g of magnesium nitrate R in water R and
◊Second identification : A, B, D. dilute to 100 mL with the same solvent. Alternatively, use
A. Freezing point (2.2.18) : minimum 53 °C, determined on an appropriate matrix modifier as recommended by the
the residue obtained in the preparation of solution S (see graphite furnace atomic absorption (GFAA) spectrometer
Tests). manufacturer.
B. Acid value (2.5.1) : 195 to 210. Test solution. Place 0.100 g of the substance to be examined
Dissolve 0.200 g of the residue obtained in the preparation in a polytetrafluoroethylene digestion bomb and add 2.5 mL
of solution S in 25 mL of the prescribed mixture of of cadmium- and lead-free nitric acid R. Close and seal the
solvents.◊ bomb according to the manufacturer’s operating instructions
(when using a digestion bomb, be thoroughly familiar with the
C. Examine the chromatograms obtained in the assay of
safety and operating instructions. Carefully follow the bomb
stearic acid and palmitic acid.
manufacturer’s instructions regarding care and maintenance
Results : the 2 principal peaks in the chromatogram of these digestion bombs. Do not use metal jacketed bombs
obtained with the test solution are similar in retention time or liners which have been used with hydrochloric acid due
to the 2 principal peaks in the chromatogram obtained to contamination from corrosion of the metal jacket by
with the reference solution. hydrochloric acid). Heat the bomb in an oven at 170 °C for 3 h.
D. To 1 mL of solution S add 1 mL of dilute ammonia R1 ; Cool the bomb slowly in air to room temperature according
a white precipitate is formed that dissolves on addition to the bomb manufacturer’s instructions. Place the bomb in a
of 1 mL of ammonium chloride solution R. Add 1 mL fume cupboard and open carefully as corrosive gases may be
of a 120 g/L solution of disodium hydrogen phosphate expelled. Dissolve the residue in water R and dilute to 10.0 mL
dodecahydrate R ; a white crystalline precipitate is formed. with the same solvent.
TESTS Reference solution. Prepare a solution of 0.0030 μg/mL of Cd
by suitable dilutions of a 0.00825 μg/mL solution of cadmium
Solution S. To 5.0 g add 50 mL of peroxide-free ether R, 20 mL nitrate tetrahydrate R in the blank solution.
of dilute nitric acid R and 20 mL of water R and heat under a
reflux condenser until dissolution is complete. Allow to cool. Dilute 1.0 mL of the test solution to 10.0 mL with the blank
In a separating funnel, separate the aqueous layer and shake solution. Prepare mixtures of this solution, the reference
the ether layer with 2 quantities, each of 4 mL, of water R. solution and the blank solution in the following proportions :
Combine the aqueous layers, wash with 15 mL of peroxide-free (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
ether R and dilute to 50.0 mL with water R (solution S). each mixture add 50 μL of modifier solution and mix. These
Evaporate the organic layer to dryness and dry the residue at solutions contain respectively 0 μg, 0.00075 μg and 0.0015 μg
100-105 °C. Keep the residue for identification tests A and B. of cadmium per millilitre from the reference solution (keep the
remaining test solution for use in the test for lead and nickel).
Acidity or alkalinity. To 1.0 g add 20 mL of carbon
dioxide-free water R and boil for 1 min with continuous Source : cadmium hollow-cathode lamp.
shaking. Cool and filter. To 10 mL of the filtrate add 0.05 mL Wavelength : 228.8 nm.
of bromothymol blue solution R4. Not more than 0.05 mL of
0.1 M hydrochloric acid or 0.1 M sodium hydroxide is required Atomisation device : furnace.
to change the colour of the indicator. Platform : pyrolytically coated with integrated tube.
(1) This monograph has undergone pharmacopoeial harmonisation. See chapter 5.8. Pharmacopoeial harmonisation.

General Notices (1) apply to all monographs and other texts 3163
Magnesium stearate EUROPEAN PHARMACOPOEIA 10.0

Operating conditions : use the temperature programme Test solution. Use the solution described in the test for
recommended for cadmium by the GFAA spectrometer cadmium.
manufacturer. An example of temperature parameters for Reference solution. Prepare a solution of 0.050 μg/mL of Ni by
GFAA analysis of cadmium is shown below. suitable dilutions of a 0.2477 μg/mL solution of nickel nitrate
Stage Final temperature Ramp time Hold time hexahydrate R in the blank solution.
(°C) (s) (s) Prepare mixtures of the test solution, the reference solution
Drying 110 10 20 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
Ashing 600 10 30 each mixture add 50 μL of matrix modifier solution and mix.
Atomisation 1800 0 5 These reference solutions contain respectively 0 μg, 0.0125 μg
and 0.025 μg of nickel per millilitre from the reference
Lead : maximum 10 ppm. solution.
Atomic absorption spectrometry (2.2.23, Method II). Source : nickel hollow-cathode lamp.
For the preparation of all aqueous solutions and for the rinsing Wavelength : 232.0 nm.
of glassware before use, employ water that has been passed Atomisation device : furnace.
through a strong-acid, strong-base, mixed-bed ion-exchange Platform : pyrolytically coated with integrated tube.
resin before use. Select all reagents to have as low a content of Operating conditions : use the temperature programme
cadmium, lead and nickel as practicable and store all reagent recommended for nickel by the GFAA spectrometer
solutions in containers of borosilicate glass. Clean glassware manufacturer. An example of temperature parameters for
before use by soaking in a warm 773 g/L solution of nitric GFAA analysis of nickel is shown below.
acid R for 30 min and by rinsing with deionised water.
Stage Final temperature Ramp time Hold time
Blank solution. Use the solution described in the test for
(°C) (s) (s)
cadmium.
Drying 110 10 20
Modifier solution. Use the solution described in the test for
cadmium. Ashing 1000 20 30
Test solution. Use the solution described in the test for Atomisation 2300 0 5
cadmium.
Reference solution. Prepare a solution of 0.100 μg/mL of Pb by Loss on drying (2.2.32) : maximum 6.0 per cent, determined
suitable dilutions of lead standard solution (100 ppm Pb) R on 1.000 g by drying in an oven at 105 °C.
with the blank solution. ♦Microbial contamination.
Prepare mixtures of the test solution, the reference solution TAMC : acceptance criterion 103 CFU/g (2.6.12).
and the blank solution in the following proportions : TYMC : acceptance criterion 102 CFU/g (2.6.12).
(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
Absence of Escherichia coli (2.6.13).
each mixture add 50 μL of modifier solution and mix. These
solutions contain respectively 0 μg, 0.025 μg and 0.05 μg of Absence of Salmonella (2.6.13).♦
lead per millilitre from the reference solution. ASSAY
Source : lead hollow-cathode lamp.
Magnesium. To 0.500 g in a 250 mL conical flask add
Wavelength : 283.3 nm. 50 mL of a mixture of equal volumes of anhydrous ethanol R
Atomisation device : furnace. and butanol R, 5 mL of concentrated ammonia R, 3 mL of
Platform : pyrolytically coated with integrated tube. ammonium chloride buffer solution pH 10.0 R, 30.0 mL
of 0.1 M sodium edetate and 15 mg of mordant black 11
Operating conditions : use the temperature programme triturate R. Heat at 45-50 °C until the solution is clear and
recommended for lead by the GFAA spectrometer titrate with 0.1 M zinc sulfate until the colour changes from
manufacturer. An example of temperature parameters for blue to violet. Carry out a blank titration.
GFAA analysis of lead is shown below.
1 mL of 0.1 M sodium edetate is equivalent to 2.431 mg of Mg.
Stage Final temperature Ramp time Hold time Stearic acid and palmitic acid. Gas chromatography (2.2.28) :
(°C) (s) (s) use the normalisation procedure.
Drying 110 10 20
Test solution. In a conical flask fitted with a reflux condenser,
Ashing 450 10 30 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
10 min. Allow to cool. Add 20 mL of saturated sodium
Atomic absorption spectrometry (2.2.23, Method II). chloride solution R. Shake and allow the layers to separate.
For the preparation of all aqueous solutions and for the rinsing Dry the organic layer over 0.1 g of anhydrous sodium sulfate R
of glassware before use, employ water that has been passed (previously washed with heptane R). Dilute 1.0 mL of the
through a strong-acid, strong-base, mixed-bed ion-exchange solution to 10.0 mL with heptane R.
resin before use. Select all reagents to have as low a content of Reference solution. Prepare the reference solution in the same
cadmium, lead and nickel as practicable and store all reagent manner as the test solution using 50.0 mg of palmitic acid CRS
solutions in containers of borosilicate glass. Clean glassware and 50.0 mg of stearic acid CRS instead of the substance to
before use by soaking in a warm 773 g/L solution of nitric be examined.
acid R for 30 min and by rinsing with deionised water. Column :
Blank solution. Use the solution described in the test for – material : fused silica ;
cadmium.
– size : l = 30 m, Ø = 0.32 mm ;
Modifier solution. Dissolve 20 g of ammonium dihydrogen
– stationary phase : macrogol 20 000 R (film thickness 0.5 μm).
phosphate R in water R and dilute to 100 mL with the same
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.

3164 See the information section on general monographs (cover pages)


EUROPEAN PHARMACOPOEIA 10.0 Magnesium trisilicate

Temperature : Solubility : freely soluble in water, very soluble in boiling water,


Time Temperature
practically insoluble in ethanol (96 per cent).
(min) (°C) IDENTIFICATION
Column 0-2 70
A. It gives the reactions of sulfates (2.3.1).
2 - 36 70 → 240 B. It gives the reaction of magnesium (2.3.1).
36 - 41 240
TESTS
Injection port 220 Solution S. Dissolve 5.0 g in water R and dilute to 50 mL
Detector 260 with the same solvent.
Appearance of solution. Solution S is clear (2.2.1) and
Detection : flame ionisation. colourless (2.2.2, Method II).
Injection : 1 μL. Acidity or alkalinity. To 10 mL of solution S add 0.05 mL
Relative retention with reference to methyl stearate : methyl of phenol red solution R. Not more than 0.2 mL of 0.01 M
palmitate = about 0.9. hydrochloric acid or 0.01 M sodium hydroxide is required to
System suitability : reference solution : change the colour of the indicator.
– resolution : minimum 5.0 between the peaks due to methyl Chlorides (2.4.4) : maximum 300 ppm.
palmitate and methyl stearate ; Dilute 1.7 mL of solution S to 15 mL with water R.
– relative standard deviation : maximum 3.0 per cent for the
areas of the peaks due to methyl palmitate and methyl Arsenic (2.4.2, Method A) : maximum 2 ppm, determined on
stearate, determined on 6 injections ; maximum 1.0 per 0.5 g.
cent for the ratio of the areas of the peaks due to methyl Iron (2.4.9) : maximum 20 ppm.
palmitate to the areas of the peaks due to methyl stearate, Dilute 5 mL of solution S to 10 mL with water R.
determined on 6 injections.
Loss on drying (2.2.32) : 48.0 per cent to 52.0 per cent,
FUNCTIONALITY-RELATED CHARACTERISTICS determined on 0.500 g by drying in an oven at 110-120 °C for
This section provides information on characteristics that are 1 h and then at 400 °C to constant mass.
recognised as being relevant control parameters for one or ASSAY
more functions of the substance when used as an excipient
(see chapter 5.15). Some of the characteristics described in Dissolve 0.450 g in 100 mL of water R and carry out the
the Functionality-related characteristics section may also be complexometric titration of magnesium (2.5.11).
present in the mandatory part of the monograph since they 1 mL of 0.1 M sodium edetate is equivalent to 12.04 mg
also represent mandatory quality criteria. In such cases, a of MgSO4.
cross-reference to the tests described in the mandatory part is
included in the Functionality-related characteristics section.
Control of the characteristics can contribute to the quality 01/2017:0403
of a medicinal product by improving the consistency of the
manufacturing process and the performance of the medicinal
product during use. Where control methods are cited, they are
recognised as being suitable for the purpose, but other methods
can also be used. Wherever results for a particular characteristic MAGNESIUM TRISILICATE
are reported, the control method must be indicated.
The following characteristics may be relevant for magnesium Magnesii trisilicas
stearate used as lubricant in tablets and capsules.
Particle-size distribution (2.9.31). DEFINITION
Specific surface area (2.9.26, Method I). Determine the It has a variable composition corresponding approximately
specific surface area in the P/Po range of 0.05 to 0.15. to Mg2Si3O8,xH2O.
Sample outgassing : 2 h at 40 °C. Content :
– magnesium oxide (MgO ; Mr 40.30) : minimum 29.0 per
Thermogravimetry (2.2.34). cent (ignited substance),
– silicon dioxide (SiO2 ; Mr 60.1) : minimum 65.0 per cent
01/2017:0044 (ignited substance).
CHARACTERS
Appearance : white or almost white powder.
Solubility : practically insoluble in water and in ethanol (96 per
MAGNESIUM SULFATE cent).
HEPTAHYDRATE IDENTIFICATION
Magnesii sulfas heptahydricus A. 0.25 g gives the reaction of silicates (2.3.1).
B. 1 mL of solution S (see Tests) neutralised with dilute sodium
MgSO4,7H2O Mr 246.5 hydroxide solution R gives the reaction of magnesium
[10034-99-8] (2.3.1).

DEFINITION TESTS
Content : 99.0 per cent to 100.5 per cent (dried substance). Solution S. To 2.0 g add a mixture of 4 mL of nitric acid R
and 4 mL of distilled water R. Heat to boiling with frequent
CHARACTERS shaking. Add 12 mL of distilled water R and allow to cool.
Appearance : white or almost white, crystalline powder or Filter or centrifuge to obtain a clear solution and dilute to
brilliant, colourless crystals. 20 mL with distilled water R.

General Notices (1) apply to all monographs and other texts 3165