Magnesium Stearate
Octadecanoic acid, magnesium salt;
Magnesium stearate
[557-04-0].
221
:
A 
6.0-mLNF30 portion of the Sample solution prepared in Identification test A shows no more sulfate than corresponds to 3.0 mL of 0.020 N sulfuric acid (1.0%).
• Lead 251
• Limit of Cadmium
• Limit of Lead
• Limit of Nickel
Labeling:
Where the labeling states the specific surface area, it also indicates which method specified in Specific Surface Area 846 is used. Label to indicate that the fatty acids are derived from edible sources.NF30
(mag nee' zee um steer' ate).
Portions of the monograph text that are national USP text, and are not part of the harmonized text, are marked with symbols () to specify this fact.
) to specify this fact.Octadecanoic acid, magnesium salt;
Magnesium stearate
[557-04-0].DEFINITION
Magnesium Stearate is a compound of magnesium with a mixture of solid organic acids, and consists chiefly of variable proportions of magnesium stearate and magnesium palmitate. The fatty acids are derived from edible sources. It contains NLT 4.0% and NMT 5.0% of Mg, calculated on the dried basis.
IDENTIFICATION
• A. Identification Tests—General, Magnesium 191
191
Sample solution:
Mix 5.0 g with 50 mL of peroxide-free ether, 20 mL of diluted nitric acid, and 20 mL of water in a round-bottom flask. Connect the flask to a reflux condenser, and reflux until dissolution is complete. Allow to cool, and transfer the contents of the flask to a separator. Shake, allow the layers to separate, and transfer the aqueous layer to a flask. Extract the ether layer with two 4-mL portions of water, and add these aqueous extracts to the main aqueous extract. Wash the aqueous extract with 15 mL of peroxide-free ether, transfer the aqueous extract to a 50-mL volumetric flask, and dilute with water to volume. Retain the unused portion of this solution for the chloride and sulfate impurity tests.
Acceptance criteria:
The Sample solution meets the requirements.
• B.
The retention times of the peaks corresponding to stearic acid and palmitic acid of the Sample solution correspond to those of the System suitability solution, as obtained in the test for Relative Content of Stearic Acid and Palmitic Acid.
ASSAY
• Procedure
Buffer:
Dissolve 5.4 g of ammonium chloride in water, add 20 mL of ammonium hydroxide, and dilute with water to 100 mL.
Sample:
500 mg
Analysis:
To the Sample add 50 mL of a mixture of butyl alcohol and dehydrated alcohol (1:1), 5 mL of ammonium hydroxide, 3 mL of Buffer, 30.0 mL of 0.1 M edetate disodium VS, and 1 or 2 drops of eriochrome black TS. Heat at 45
–50 until the solution is clear. Cool, and titrate the excess edetate disodium with 0.1 M zinc sulfate VS until the solution color changes from blue to violet (see Titrimetry 541). Perform a blank determination, and make any necessary correction. Each mL of 0.1 M edetate disodium is equivalent to 2.431 mg of Mg.
–50 until the solution is clear. Cool, and titrate the excess edetate disodium with 0.1 M zinc sulfate VS until the solution color changes from blue to violet (see Titrimetry 541). Perform a blank determination, and make any necessary correction. Each mL of 0.1 M edetate disodium is equivalent to 2.431 mg of Mg.
Acceptance criteria:
4.0%–5.0% on the dried basis
IMPURITIES
• Chloride and Sulfate, Chloride 221:
A 10.0-mL portion of the Sample solution prepared in Identification test A shows no more chloride than corresponds to 1.4 mL of 0.020 N hydrochloric acid (0.1%).
221:
A 10.0-mL portion of the Sample solution prepared in Identification test A shows no more chloride than corresponds to 1.4 mL of 0.020 N hydrochloric acid (0.1%).
Change to read:
• Chloride and Sulfate, Sulfate 221:
A 6.0-mLNF30 portion of the Sample solution prepared in Identification test A shows no more sulfate than corresponds to 3.0 mL of 0.020 N sulfuric acid (1.0%).
Delete the following:
• Lead 251
Standard solution:
To 20 mL of 0.2 N nitric acid add 5 µg of lead, 4 mL of Ammonia-Cyanide Solution, and 2 drops of Hydroxylamine Hydrochloride Solution, and shake with 10.0 mL of Standard Dithizone Solution for 30 s. Pass through an acid-washed filter paper into a color-comparison tube.
Sample solution:
Ignite 0.50 g of Magnesium Stearate in a silica crucible in a muffle furnace at 475–500 for 15–20 min. Cool, add 3 drops of nitric acid, evaporate over a low flame to dryness, and again ignite at 475–500 for 30 min. Dissolve the residue in 1 mL of a mixture of equal parts by volume of nitric acid and water, and wash into a separator with several successive portions of water. Add 3 mL of Ammonium Citrate Solution and 0.5 mL of Hydroxylamine Hydrochloride Solution, and render alkaline to phenol red TS with ammonium hydroxide. Add 10 mL of Potassium Cyanide Solution. Immediately extract the solution with successive 5-mL portions of Dithizone Extraction Solution, draining off each extract into another separator, until the last portion of dithizone solution retains its green color. Shake the combined extracts for 30 s with 20 mL of 0.2 N nitric acid, and discard the chloroform layer. Add to the acid solution 4.0 mL of Ammonia-Cyanide Solution and 2 drops of Hydroxylamine Hydrochloride Solution. Add 10.0 mL of Standard Dithizone Solution, and shake the mixture for 30 s. Pass the chloroform layer through an acid-washed filter paper into a color-comparison tube.
–500 for 15–20 min. Cool, add 3 drops of nitric acid, evaporate over a low flame to dryness, and again ignite at 475–500 for 30 min. Dissolve the residue in 1 mL of a mixture of equal parts by volume of nitric acid and water, and wash into a separator with several successive portions of water. Add 3 mL of Ammonium Citrate Solution and 0.5 mL of Hydroxylamine Hydrochloride Solution, and render alkaline to phenol red TS with ammonium hydroxide. Add 10 mL of Potassium Cyanide Solution. Immediately extract the solution with successive 5-mL portions of Dithizone Extraction Solution, draining off each extract into another separator, until the last portion of dithizone solution retains its green color. Shake the combined extracts for 30 s with 20 mL of 0.2 N nitric acid, and discard the chloroform layer. Add to the acid solution 4.0 mL of Ammonia-Cyanide Solution and 2 drops of Hydroxylamine Hydrochloride Solution. Add 10.0 mL of Standard Dithizone Solution, and shake the mixture for 30 s. Pass the chloroform layer through an acid-washed filter paper into a color-comparison tube.
Analysis:
Compare the color of the Sample solution to that of the Standard solution.
Acceptance criteria:
The color of the Sample solution does not exceed that of the Standard solution (10 ppm).NF30
NF30
Add the following:
• Limit of Cadmium
[Note—For the preparation of all aqueous solutions and for the rinsing of glassware before use, use water that has been passed through a strong-acid, strong-base, mixed-bed ion-exchange resin. Select all reagents to have as low a content of cadmium, lead, and nickel as practicable, and store all reagent solutions in containers of borosilicate glass. Cleanse glassware before use by soaking in warm 8 N nitric acid for 30 min, and rinse with deionized water. ]
Matrix modifier solution:
Prepare a solution containing 200 mg/mL of monobasic ammonium phosphate and 10 mg/mL of magnesium nitrate. Alternatively, use an appropriate matrix modifier as recommended by the manufacturer of the graphite furnace atomic absorption (GFAA) spectrophotometer.
Blank:
Nitric acid in water (1 in 4)
Standard solution:
0.00825 µg/mL of cadmium nitrate tetrahydrate in Blank, corresponding to a known concentration of 0.0030 µg/mL of cadmium
Sample stock solution:
Transfer 0.100 g of Magnesium Stearate to a suitable polytetrafluoroethylene (PTFE)-lined acid-digestion bomb, and add 2.5 mL of nitric acid. Close and seal the bomb according to the manufacturer's operating instructions. [Caution—When using an acid-digestion bomb, be thoroughly familiar with the safety and operating instructions. Carefully follow the bomb manufacturer's instructions regarding care and maintenance of these acid-digestion bombs. Do not use metal-jacketed bombs or liners that have been used with hydrochloric acid because of contamination from corrosion of the metal jacket by hydrochloric acid.
] Heat the bomb in an oven at 170 for 3 h. Air cool the bomb slowly to room temperature as per the bomb manufacturer's instructions. Place the bomb in a hood, and open carefully because corrosive gases may be expelled. Dilute the residue with water to 10.0 mL in a volumetric flask.
for 3 h. Air cool the bomb slowly to room temperature as per the bomb manufacturer's instructions. Place the bomb in a hood, and open carefully because corrosive gases may be expelled. Dilute the residue with water to 10.0 mL in a volumetric flask.
Sample solutions:
Dilute the Sample stock solution with Blank (1 in 10). Prepare mixtures of this solution, the Standard solution, and the Blank with the following proportional compositions, by volume (mL): 1.0/0/1.0, 1.0/0.5/0.5, and 1.0/1.0/0. Add 50 µL of Matrix modifier solution to each mixture. These Sample solutions contain, respectively, 0, 0.00075, and 0.0015 µg/mL of cadmium from the Standard solution. [Note—Retain the remaining Sample stock solution for use in the tests for Limit of Lead and Limit of Nickel. ]
Instrumental conditions
Mode:
Atomic absorption spectrophotometry (using a suitable GFAA spectrophotometer equipped with a pyrolytic tube with platform)
Analytical wavelength:
Cadmium emission line at 228.8 nm
Lamp:
Cadmium hollow-cathode
Temperature:
Use the temperature programming recommended for cadmium by the GFAA manufacturer (for examples of temperature parameters for GFAA analysis of cadmium, see Table 1).
Table 1
| Drying Stage | Ashing Stage | Atomization Stage | |
|---|---|---|---|
| Temperature | 110 |
600 |
1800 |
| Ramp time | 10 s | 10 s | 0 s |
| Hold time | 20 s | 30 s | 5 s |
Analysis:
Use the Blank to set the instrument to zero. Plot the absorbances of the Sample solutions versus their contents of cadmium, in µg/mL, as furnished by the Standard solution, draw the straight line best fitting the three points, using a linear least-squares fit, and extrapolate the line until it intercepts the concentration axis on the negative side. From the intercept determine the concentration, C, in µg/mL, of cadmium in the Sample solution containing 0 mL of the Standard solution.
Alternatively, the GFAA software can be used to calculate the cadmium content of the sample. For either calculation, the correlation coefficient (r) of the standard additions plot must be at least 0.995.
Calculate the content, in ppm, of cadmium in the specimen taken:
Result = (C/W) × F
| W | = | = weight of Magnesium Stearate taken to prepare the Sample stock solution (g) |
| F | = | = dilution factor for the sample, 200 |
Acceptance criteria:
3 ppmNF30
NF30
Add the following:
• Limit of Lead
[Note—For the preparation of all aqueous solutions and for the rinsing of glassware before use, use water that has been passed through a strong-acid, strong-base, mixed-bed ion-exchange resin. Select all reagents to have as low a content of cadmium, lead, and nickel as practicable, and store all reagent solutions in containers of borosilicate glass. Cleanse glassware before use by soaking in warm 8 N nitric acid for 30 min, and rinse with deionized water. ]
Matrix modifier solution:
Prepare as directed for Matrix modifier solution in Limit of Cadmium.
Blank:
Prepare as directed for Blank in Limit of Cadmium.
Standard solution:
0.1598 µg/mL of lead nitrate in Blank, corresponding to a known concentration of 0.100 µg/mL of lead. Prepare and store any solutions of lead nitrate in glass containers free from soluble lead salts.
Sample stock solution:
Use a portion of the Sample stock solution retained from the test for Limit of Cadmium.
Sample solutions:
Prepare mixtures of the Sample stock solution, the Standard solution, and the Blank with the following proportional compositions, by volume (mL): 1.0/0/1.0, 1.0/0.5/0.5, and 1.0/1.0/0. Add 50 µL of the Matrix modifier solution to each mixture. These Sample solutions contain, respectively, 0, 0.025, and 0.05 µg/mL of lead from the Standard solution.
Instrumental conditions
Mode:
Atomic absorption spectrophotometry (using a suitable GFAA spectrophotometer equipped with a pyrolytic tube with platform)
Analytical wavelength:
Lead emission line at 283.3 nm
Lamp:
Lead hollow-cathode
Temperature:
Use the temperature programming recommended for lead by the GFAA manufacturer (for examples of temperature parameters for GFAA analysis of lead, see Table 1).
Analysis:
Use the Blank to set the instrument to zero. Plot the absorbances of the Sample solutions versus their contents of lead, in µg/mL, as furnished by the Standard solution, draw the straight line best fitting the three points, using a linear least-squares fit, and extrapolate the line until it intercepts the concentration axis on the negative side. From the intercept determine the concentration, C, in µg/mL, of lead in the Sample solution containing 0 mL of the Standard solution.
Alternatively, the GFAA software can be used to calculate the lead content of the sample. For either calculation, the correlation coefficient (r) of the standard additions plot must be at least 0.995.
Calculate the content, in ppm, of lead in the specimen taken:
Result = (C/W) × F
| W | = | = weight of Magnesium Stearate taken to prepare the Sample stock solution (g) |
| F | = | = dilution factor for the sample, 20 |
Acceptance criteria:
10 ppmNF30
NF30
Add the following:
• Limit of Nickel
[Note—For the preparation of all aqueous solutions and for the rinsing of glassware before use, use water that has been passed through a strong-acid, strong-base, mixed-bed ion-exchange resin. Select all reagents to have as low a content of cadmium, lead, and nickel as practicable, and store all reagent solutions in containers of borosilicate glass. Cleanse glassware before use by soaking in warm 8 N nitric acid for 30 min, and rinse with deionized water. ]
Matrix modifier solution:
Prepare as directed for Matrix modifier solution in Limit of Cadmium.
Blank:
Prepare as directed for Blank in Limit of Cadmium.
Standard solution:
0.2477 µg/mL of nickel nitrate hexahydrate in Blank, corresponding to a known concentration of 0.050 µg/mL of nickel
Sample stock solution:
Use a portion of the Sample stock solution retained from the test for Limit of Cadmium.
Sample solutions:
Prepare mixtures of the Sample stock solution, the Standard solution, and the Blank with the following proportional compositions, by volume (mL): 1.0/0/1.0, 1.0/0.5/0.5, and 1.0/1.0/0. Add 50 µL of the Matrix modifier solution to each mixture. These Sample solutions contain, respectively, 0, 0.0125, and 0.025 µg/mL of nickel from the Standard solution.
Instrumental conditions
Mode:
Atomic absorption spectrophotometry (using a suitable GFAA spectrophotometer equipped with a pyrolytic tube with platform)
Analytical wavelength:
Nickel emission line at 232.0 nm
Lamp:
Nickel hollow-cathode
Temperature:
Use the temperature programming recommended for nickel by the GFAA manufacturer (for examples of temperature parameters for GFAA analysis of nickel, see Table 1).
Analysis:
Use the Blank to set the instrument to zero. Plot the absorbances of the Sample solutions versus their contents of nickel, in µg/mL, as furnished by the Standard solution, draw the straight line best fitting the three points, using a linear least-squares fit, and extrapolate the line until it intercepts the concentration axis on the negative side. From the intercept determine the concentration, C, in µg/mL, of nickel in the Sample solution containing 0 mL of the Standard solution.
Alternatively, the GFAA software can be used to calculate the nickel content of the sample. For either calculation, the correlation coefficient (r) of the standard additions plot must be at least 0.995.
Calculate the content, in ppm, of nickel in the specimen taken:
Result = (C/W) × F
| W | = | = weight of Magnesium Stearate taken to prepare the Sample stock solution (g) |
| F | = | = dilution factor for the sample, 20 |
Acceptance criteria:
5 ppmNF30
NF30
SPECIFIC TESTS
• Microbial Enumeration Tests 61 and Tests for Specified Microorganisms 62:
The total aerobic microbial count does not exceed 103 cfu/g, the total combined molds and yeasts count does not exceed 5 × 102 cfu/g. It meets the requirements of the tests for absence of Salmonella species and Escherichia coli.
61 and Tests for Specified Microorganisms 62:
The total aerobic microbial count does not exceed 103 cfu/g, the total combined molds and yeasts count does not exceed 5 × 102 cfu/g. It meets the requirements of the tests for absence of Salmonella species and Escherichia coli.
• Acidity or Alkalinity
Sample solution:
To 1.0 g add 20 mL of carbon dioxide-free water, boil on a steam bath for 1 min with continuous shaking, cool, and filter. Add 0.05 mL of bromothymol blue TS to 10 mL of the filtrate.
Acceptance criteria:
NMT 0.05 mL of 0.1 N hydrochloric acid or 0.1 N sodium hydroxide is required to change the color of the indicator.
• Specific Surface Area 846
Specific Surface Area 846
[Note—In cases where there are no functionality-related concerns regarding the specific surface area of this article, this test may be omitted. ]
Where the labeling states the specific surface area, determine the specific surface area value as directed in the chapter in the P/P0 range of 0.05–0.15, and using outgassing conditions of 2 h at 40. If the plot deviates from linearity for P/P0 values of 0.05–0.15, then a suitable range of P/P0 values should be validated for linearity. In this case, it is necessary to state the range of validated P/P0 values, the increment of the P/P0 values, and the outgassing conditions used.
. If the plot deviates from linearity for P/P0 values of 0.05–0.15, then a suitable range of P/P0 values should be validated for linearity. In this case, it is necessary to state the range of validated P/P0 values, the increment of the P/P0 values, and the outgassing conditions used.
• Loss on Drying 731:
Dry a sample at 105 to constant weight: it loses NMT 6.0% of its weight.
731:
Dry a sample at 105 to constant weight: it loses NMT 6.0% of its weight.
Change to read:
• Relative Content of Stearic Acid and Palmitic Acid
System suitability solution:
Transfer 50 mg each of USP Stearic Acid RS and USP Palmitic Acid RS to a small conical flask fitted with a suitable reflux condenser. Add 5.0 mL of a solution prepared by dissolving 14 g of boron trifluoride in methanol to make 100 mL, swirl to mix, and reflux for 10 min until the solids have dissolved. Add 4 mL of chromatographic n-heptane through the condenser, and reflux for 10 min. Cool, add 20 mL of saturated sodium chloride solution, shake, and allow the layers to separate. Pass the n-heptane layer through 0.1 g of anhydrous sodium sulfate (previously washed with chromatographic n-heptane) into a suitable flask. Transfer 1.0 mL of this solution to a 10-mL volumetric flask, and dilute with chromatographic n-heptane to volume.
Sample solution:
Transfer 100 mg of Magnesium Stearate to a small conical flask fitted with a suitable reflux condenser, and proceed as directed for System suitability solution, beginning with “Add 5.0 mL of a solution prepared by dissolving”.
Chromatographic system
Flow rate:
2.4 mL/minNF30
Mode:
GC
Detector:
Flame ionization
Column:
0.32-mm × 30-m fused silica capillary column, bonded with a 0.5-µm layer of phase G16
Temperature
Injector:
220
Detector:
260
Column:
See Table 2.
Table 2
| Initial Temperature ( ) |
Temperature Ramp ( /min) |
Final Temperature ( ) |
Hold Time at Final Temperature (min) |
|---|---|---|---|
| 70 | — | 70 | 2 |
| 70 | 5 | 240 | 5 |
Carrier gas:
Helium
Flow rate:
2.4 mL/minNF30
Injection size:
1 µL
Injection type:
Splitless injection system
System suitability
Sample:
System suitability solution
[Note—The relative retention times for methyl palmitate and methyl stearate are about 0.9NF30 and 1.0, respectively. ]
0.9NF30 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 5.0 between methyl palmitate and methyl stearate
Relative standard deviation:
NMT 3.0% for the palmitate and stearate peak areas from six replicate injections and NMT 1.0% for the peak area ratio of palmitate to stearate from six replicate injectionsNF30
NMT 3.0% for the palmitate and stearate peak areas from six replicate injections and NMT 1.0% for the peak area ratio of palmitate to stearate from six replicate injectionsNF30
Analysis
Sample:
Sample solution
Measure the peak areas for all the fatty acid esters in the chromatogram.
Calculate the percentage of stearic acid in the fatty acid fraction of the portion of Magnesium Stearate taken:
Result = (rU/rT) × 100
| rU | = | = peak area due to methyl stearate |
| rT | = | = sum of the peak areas of all the fatty acid esters |
Similarly, calculate the percentage of palmitic acid in the portion of Magnesium Stearate taken.
Result = (rP/rT) × 100
| rP | = | = peak area due to methyl palmitate |
| rT | = | = sum of the areas of all the fatty acid ester peaks |
Acceptance criteria:
NLT 40% for the stearate peak. The sum of the stearate and palmitate peaks is NLT 90% of the total peak areas of all the fatty acids.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers.
Change to read:
• Labeling:
Where the labeling states the specific surface area, it also indicates which method specified in Specific Surface Area 846 is used. Label to indicate that the fatty acids are derived from edible sources.NF30
') + '&img=../../images/v35300/cas-57-10-3.gif',600,500);)
') + '&img=../../images/v35300/cas-57-11-4.gif',600,500);)
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Robert H. Lafaver, M.S.
Scientific Liaison 1-301-816-8335 |
(EXC2010) Monographs - Excipients |
| 61 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 62 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 1847
Pharmacopeial Forum: Volume No. 30(1) Page 340