Magnesium Stearate
Octadecanoic acid,magnesium salt.
Magnesium stearate [557-04-0].
»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 not less than 4.0percent and not more than 5.0percent of Mg,calculated on the dried basis.
Packaging and storage—
Preserve in tight containers.
Labeling—
Where the labeling states the specific surface area,it also indicates which method specified under Specific Surface Area á846ñis used.
Identification—
A:
Mix 5.0g with 50mLof peroxide-free ether,20mLof diluted nitric acid,and 20mLof 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-mLportions of water,and add these aqueous extracts to the main aqueous extract.Wash the aqueous extract with 15mLof peroxide-free ether,transfer the aqueous extract to a 50-mLvolumetric flask,dilute with water to volume,and mix.Retain this solution for the Limit of chlorideand Limit of sulfatetests.This solution responds to the test for Magnesium á191ñ.
B:
The retention times of the peaks corresponding to stearic acid and palmitic acid in the chromatogram of the Test solutioncorrespond to those in the chromatogram of the System suitability solution,as obtained in the Relative content of stearic acid and palmitic acidtest.
Microbial limits á61ñ—
The total aerobic microbial count does not exceed 1000cfu per g,the total combined molds and yeasts count does not exceed 500cfu per g,and it meets the requirements of the tests for absence of Salmonellaspecies and Escherichia coli.
Acidity or alkalinity—
Transfer 1.0g to a 100-mLbeaker,add 20mLof carbon dioxide-free water,boil on a steam bath for 1minute with continuous shaking,cool,and filter.Add 0.05mLof bromothymol blue TSto 10mLof the filtrate:not more than 0.05mLof 0.1Nhydrochloric acid or 0.1Nsodium hydroxide is required to change the color of the indicator.
Loss on drying á731ñ—
Dry it at 105
to constant weight:it loses not more than 6.0%of its weight.
to constant weight:it loses not more than 6.0%of its weight.
Specific surface area á846ñ—
[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/P0range of 0.05to 0.15,and using outgassing conditions of 2hours at 40.If the plot deviates from linearity for P/P0values of 0.05to 0.15,then a suitable range of P/P0values should be validated for linearity.In this case,it is necessary to state the range of validated P/P0values,the increment of the P/P0values,and the outgassing conditions employed.
.If the plot deviates from linearity for P/P0values of 0.05to 0.15,then a suitable range of P/P0values should be validated for linearity.In this case,it is necessary to state the range of validated P/P0values,the increment of the P/P0values,and the outgassing conditions employed.
Limit of chloride á221ñ—
A10.0-mLportion of the aqueous solution obtained in Identificationtest Ashows no more chloride than corresponds to 1.4mLof 0.020Nhydrochloric acid (0.1%).
Limit of sulfate á221ñ—
A3.0mLportion of the aqueous solution obtained in Identificationtest Ashows no more sulfate than corresponds to 3.0mLof 0.020Nsulfuric acid (1.0%).
Lead á251ñ—
Ignite 0.50g in a silica crucible in a muffle furnace at 475to 500for 15to 20minutes.Cool,add 3drops of nitric acid,evaporate over a low flame to dryness,and again ignite at 475to 500for 30minutes.Dissolve the residue in 1mLof a mixture of equal parts by volume of nitric acid and water,and wash into a separator with several successive portions of water.Add 3mLof Ammonium Citrate Solutionand 0.5mLof Hydroxylamine Hydrochloride Solution,and render alkaline to phenol red TSwith ammonium hydroxide.Add 10mLof Potassium Cyanide Solution.Immediately extract the solution with successive 5-mLportions 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 30seconds with 20mLof 0.2Nnitric acid,and discard the chloroform layer.Add to the acid solution 4.0mLof Ammonia-Cyanide Solutionand 2drops of Hydroxylamine Hydrochloride Solution.Add 10.0mLof Standard Dithizone Solution,and shake the mixture for 30seconds.Pass the chloroform layer through an acid-washed filter paper into a color-comparison tube,and compare the color with that of a standard solution prepared as follows.To 20mLof 0.2Nnitric acid add 5µg of lead,4mLof Ammonia-Cyanide Solution,and 2drops of Hydroxylamine Hydrochloride Solution,and shake with 10.0mLof Standard Dithizone Solutionfor 30seconds.Pass through an acid-washed filter paper into a color-comparison tube.The color of the sample solution does not exceed that of the control (0.001%).
to 500for 15to 20minutes.Cool,add 3drops of nitric acid,evaporate over a low flame to dryness,and again ignite at 475to 500for 30minutes.Dissolve the residue in 1mLof a mixture of equal parts by volume of nitric acid and water,and wash into a separator with several successive portions of water.Add 3mLof Ammonium Citrate Solutionand 0.5mLof Hydroxylamine Hydrochloride Solution,and render alkaline to phenol red TSwith ammonium hydroxide.Add 10mLof Potassium Cyanide Solution.Immediately extract the solution with successive 5-mLportions 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 30seconds with 20mLof 0.2Nnitric acid,and discard the chloroform layer.Add to the acid solution 4.0mLof Ammonia-Cyanide Solutionand 2drops of Hydroxylamine Hydrochloride Solution.Add 10.0mLof Standard Dithizone Solution,and shake the mixture for 30seconds.Pass the chloroform layer through an acid-washed filter paper into a color-comparison tube,and compare the color with that of a standard solution prepared as follows.To 20mLof 0.2Nnitric acid add 5µg of lead,4mLof Ammonia-Cyanide Solution,and 2drops of Hydroxylamine Hydrochloride Solution,and shake with 10.0mLof Standard Dithizone Solutionfor 30seconds.Pass through an acid-washed filter paper into a color-comparison tube.The color of the sample solution does not exceed that of the control (0.001%).
Organic volatile impurities,Method IVá467ñ:
meets the requirements.
Relative content of stearic acid and palmitic acid—
System suitability solution—
Transfer about 50mg each of USP Stearic Acid RSand USP Palmitic Acid RSto a small conical flask fitted with a suitable reflux condenser.Add 5.0mLof a solution prepared by dissolving 14g of boron trifluoride in methanol to make 100mL,swirl to mix,and reflux for 10minutes until the solids have dissolved.Add 4mLof chromatographic n-heptane through the condenser,and reflux for 10minutes.Cool,add 20mLof saturated sodium chloride solution,shake,and allow the layers to separate.Pass the n-heptane layer through 0.1g of anhydrous sodium sulfate (previously washed with chromatographic n-heptane)into a suitable flask.Transfer 1.0mLof this solution to a 10-mLvolumetric flask,dilute with chromatographic n-heptane to volume,and mix.
Test solution—
Transfer about 100mg of Magnesium Stearate,accurately weighed,to a small conical flask fitted with a suitable reflux condenser,and proceed as directed for System suitability solution,beginning with “Add 5.0mLof a solution prepared by dissolving.”
Chromatographic system(see Chromatography á621ñ)—
The gas chromatograph is equipped with a flame-ionization detector,maintained at about 260;a splitless injection system;and a 0.32-mm ×30-m fused silica capillary column bonded with a 0.5-µm layer of phase G16.The column temperature is maintained at 70for about 2minutes after injection,then programmed to increase at the rate of 5per minute to 240and to maintain this temperature for 5minutes.The injection port temperature is maintained at about 220.The carrier gas is helium with a linear velocity of about 50cm per second.
;a splitless injection system;and a 0.32-mm ×30-m fused silica capillary column bonded with a 0.5-µm layer of phase G16.The column temperature is maintained at 70for about 2minutes after injection,then programmed to increase at the rate of 5per minute to 240and to maintain this temperature for 5minutes.The injection port temperature is maintained at about 220.The carrier gas is helium with a linear velocity of about 50cm per second.
Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.86for methyl palmitate and 1.0for methyl stearate;the resolution,R,between the methyl palmitate and methyl stearate peaks is not less than 5.0;the relative standard deviation of the peak area responses for the palmitate and stearate peaks for replicate injections is not greater than 6.0%;and the relative standard deviation of the peak area response ratio of the palmitate to stearate peaks from these replicate injections is not more than 1.0%.
Procedure—
Inject about 1µLof the Test solutioninto the chromatograph,record the chromatogram,and measure the peak areas for all the fatty acid ester peaks in the chromatogram.Calculate the percentage of stearic acid in the fatty acid fraction of Magnesium Stearate taken by the formula:
100A/B,
in which Ais the area due to the methyl stearate peak,and Bis the sum of the areas of all the fatty acid ester peaks in the chromatogram.Similarly,calculate the percentage of palmitic acid in the portion of Magnesium Stearate taken.The stearate peak comprises not less than 40%;and the sum of the stearate and palmitate peaks is not less than 90%of the total area of all fatty acid ester peaks in the chromatogram.
Assay—
Ammonium chloride pH10buffer solution—
Dissolve 5.4g of ammonium chloride in water,add 20mLof ammonium hydroxide,and dilute with water to 100mL.
Procedure—
Transfer about 500mg of Magnesium Stearate,accurately weighed,to a 250-mLconical flask.Add 50mLof a mixture of butyl alcohol and dehydrated alcohol (1:1),5mLof ammonium hydroxide,3mLof Ammonium chloride pH10buffer solution,30.0mLof 0.1Medetate disodium VS,and 1or 2drops of eriochrome black TS,and mix.Heat at 45to 50until the solution is clear.Cool,and titrate the excess edetate disodium with 0.1Mzinc sulfate VSuntil the solution color changes from blue to violet (see Titrimetry á541ñ).Perform a blank determination,and make any necessary correction.Each mLof 0.1Medetate disodium is equivalent to 2.431mg of Mg.
to 50until the solution is clear.Cool,and titrate the excess edetate disodium with 0.1Mzinc sulfate VSuntil the solution color changes from blue to violet (see Titrimetry á541ñ).Perform a blank determination,and make any necessary correction.Each mLof 0.1Medetate disodium is equivalent to 2.431mg of Mg.
Auxiliary Information—
Staff Liaison:Justin Lane,B.S.,Scientific Associate
Expert Committee:(EMC)Excipients:Monograph Content
USP28–NF23Page 3030
Pharmacopeial Forum:Volume No.30(1)Page 340
Phone Number:1-301-816-8323