Low-Substituted Carboxymethylcellulose Sodium

Cellulose,carboxymethyl ether,sodium salt,low-substituted.
Carmellose sodium,low-substituted [9004-32-4].
»Low-Substituted Carboxymethylcellulose Sodium is the sodium salt of a partly O-(carboxymethylated)cellulose.It contains not less than 2.0percent and not more than 4.5percent of sodium (Na),calculated on the dried basis.
Labeling— When the settling volume is determined,label it to indicate the settling volume value.
Identification—
A: Shake 1g of Low-Substituted Carboxymethylcellulose Sodium with 100mLof sodium hydroxide solution (1in 10):a suspension is produced.
B: Shake 1g of Low-Substituted Carboxymethylcellulose Sodium with 50mLof water.Transfer 1mLof the mixture to a test tube,and add 1mLof water and 1mLof 1-naphthol TS.Incline the test tube,and add carefully 2mLof sulfuric acid down the side so that it forms a lower layer:a reddish-purple color develops at the interface.
C: It meets the requirements of the test for Residue on ignition.
D: The solution prepared in the test for Heavy metalsresponds to the pyroantimonate precipitate test for Sodium á191ñ.
pHá791ñ— Shake 1g of Low-Substituted Carboxymethylcellulose Sodium with 100mLof carbon dioxide–free water,and centrifuge:the pHof the suspension is between 6.0and 8.5.
Loss on drying á731ñ— Dry 1.0g of Low-Substituted Carboxymethylcellulose Sodium at 105ºfor 3hours:it loses not more than 10.0%of its weight.
Settling volume— [NOTE—The following test,which can relate to excipient function,may be carried out,depending on the intended use in the formulation.In cases where there are no concerns regarding the settling volume of this article,this test may be omitted.]Where the labeling states the settling volume,determine the settling volume as follows.In a 100-mLgraduated cylinder,transfer 20mLof isopropyl alcohol,add 5.0g of Low-Substituted Carboxymethylcellulose Sodium,and shake vigorously.Dilute with isopropyl alcohol to 30mL,then with water to 50mL,and shake vigorously.Within 15minutes,repeat the shaking three times.Allow to stand for 4hours,and determine the volume of the settled mass:it is between 15.0mLand 35.0mL.
Residue on ignition á281ñ— Determined on 1.0g of Low-Substituted Carboxymethylcellulose Sodium using a mixture of sulfuric acid and water (1:1)and an ignition temperature of 600±50:it is between 6.5%and 13.5%,calculated on the dried basis.
Water-soluble substances— Disperse 5.0g of Low-Substituted Carboxymethylcellulose Sodium in 400mLof water,and during the first 30minutes,stir for 1minute every 10minutes.Allow to stand for 1hour,and centrifuge,if necessary.Decant 100.0mLof the supernatant onto a fast filter paper in a vacuum filtration funnel,apply a vacuum,and collect 75.0mLof the filtrate.Evaporate in a tared platinum or porcelain dish,and dry at 105for 4hours:not more than 70%is found.
Heavy metals,Method IIá231ñ— To the residue obtained in the test for Residue on ignition,add 1mLof hydrochloric acid,evaporate on a water bath,and dissolve in 20mLof water [NOTE—Use this solution in Identificationtest D.]:the limit is 20µg per g.
Limit of sodium chloride and sodium glycolate—
SODIUM CHLORIDE— Transfer an accurately weighed quantity of about 5g of Low-Substituted Carboxymethylcellulose Sodium to a 250-mLconical flask,add 50mLof water and 5mLof 30%hydrogen peroxide,and heat on a water bath for 20minutes,stirring occasionally to ensure hydration.Cool,add 100mLof water and 10mLof nitric acid,and titrate,while stirring constantly with 0.05Nsilver nitrate VS,determining the endpoint potentiometrically using a silver electrode and a mercurous sulfate electrode with a potassium sulfate bridge.Calculate the percentage of sodium chloride (NaCl)in the Low-Substituted Carboxymethylcellulose Sodium taken by the formula:
584.4VN/(100–b)W,
in which 584.4is the equivalence factor for sodium chloride;Vis the volume,in mL,of silver nitrate;Nis the normality of silver nitrate;bis the percentage obtained from the test for Loss on drying,determined separately;andWis the weight,in g,of the Low-Substituted Carboxymethylcellulose Sodium taken.
SODIUM GLYCOLATE—
Test solution— Transfer an accurately weighed quantity of about 500mg of Low-Substituted Carboxymethylcellulose Sodium to a beaker,moisten thoroughly with 5mLof glacial acetic acid,add 5mLof water,and stir with a glass rod to ensure proper hydration (about 30minutes).Add 80mLof acetone while stirring,add 2g of sodium chloride,and stir for several minutes to ensure the complete precipitation of carboxymethylcellulose.Filter through a fast filter paper,previously wetted with a small amount of acetone,and collect the filtrate in a 100-mLvolumetric flask.Rinse the beaker and filter with acetone,and add the washings to the flask.Dilute the filtrate with acetone to volume,and mix.Allow to stand for 24hours without shaking,and use the clear supernatant.
Standard stock solution— Transfer 100mg of glycolic acid,previously dried overnight in a vacuum desiccator over phosphorus pentoxide and accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with water to volume,and mix.
Standard solutions— Into four identical 100-mLvolumetric flasks,transfer 0.5-mL,1.0-mL,1.5-mL,and 2.0-mLportions of the Standard stock solution,respectively.To each flask,add water to make 5mL,add 5mLof glacial acetic acid,dilute with acetone to volume,and mix.
Blank— Use an acetone solution containing 5%of glacial acetic acid and 5%water.
Procedure— Transfer 2.0mLof the Test solutionand 2.0mLof each Standard solutionto separate 25-mLvolumetric flasks.Place the uncovered flasks in a boiling water bath to remove the acetone,remove from the bath,and allow to cool.To each flask,add 5.0mLof 2,7-dihydroxynaphthalene TS,mix,add an additional 15mLof 2,7-dihydroxynaphthalene TS,and mix again.Cover the mouth of each flask with a small piece of aluminum foil,place the flasks upright in a boiling water bath for 20minutes,remove from the bath,cool,dilute with sulfuric acid to volume,and mix.Determine the absorbance of each solution at 540nm with a suitable spectrophotometer against the Blank,and prepare a standard curve using the absorbances obtained from the Standard solutions.From the standard curve and the absorbance of the Test solution,determine the weight(w),in mg,of glycolic acid in the Test solution,and calculate the percentage of sodium glycolate in the Low-Substituted Carboxymethylcellulose Sodium taken by the formula:
(1.29)10w/[(100–b)W],
in which 1.29is a factor converting glycolic acid to sodium glycolate;wis the weight,in mg,of glycolic acid from the standard curve;bis the percentage obtained from the Loss on dryingtest,determined separately;and Wis the weight,in g,of the Low-Substituted Carboxymethylcellulose Sodium taken.The sum of the percentages from the tests for Sodium chlorideand Sodium glycolateis not more than 0.5%.
Content of sodium— Calculate the percentage of sodium in the Low-Substituted Carboxymethylcellulose Sodium taken by the formula:
0.3238A,
in which 0.3238is a factor converting sodium sulfate to sodium;andAis the percentage obtained from the test for Residue on ignition,determined separately.
Auxiliary Information— Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(EMC)Excipients:Monograph Content
USP28–NF23Page 2977
Pharmacopeial Forum:Volume No.30(3)Page 966
Phone Number:1-301-816-8251