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Croscarmellose Sodium
»Croscarmellose Sodium is the sodium salt of a cross-linked,partlyO-(carboxymethylated)cellulose.
Packaging and storage— Preserve in tight containers.
Identification—
A: Mix 1g of it with 100mLof methylene blue solution (1in 250,000),stir the mixture,and allow it to settle:the Croscarmellose Sodium absorbs the methylene blue and settles as a blue,fibrous mass.
B: Mix 1g of it with 50mLof water.Transfer 1mLof the mixture to a small test tube,and add 1mLof water and 5drops of 1-naphthol TS.Incline the test tube,and carefully add 2mLof sulfuric acid down the side so that it forms a lower layer:a reddish-violet color develops at the interface.
C: Aportion of the mixture of it with water,prepared as directed inIdentification testB,responds to the flame test forSodium á191ñ.
Microbial limits á61ñ— The total aerobic microbial count does not exceed 1000cfu per g,the total combined molds and yeasts count does not exceed 100cfu per g,and it meets the requirements of the tests for absence ofEscherichia coli.
pHá791ñ— Mix 1g of it with 100mLof water for 5minutes:the pHof the dispersion is between 5.0and 7.0.
Loss on drying á731ñ— Dry it at 105ºfor 6hours:it loses not more than 10.0%of its weight.
Sodium chloride and sodium glycolate—
SODIUM CHLORIDE— Accurately weigh about 5g of it into a 250-mLbeaker,add 50mLof water and 5mLof 30%hydrogen peroxide,and heat on a steam bath for 20minutes,stirring occasionally to ensure hydration.Cool,add 100mLof water and 10mLof nitric acid,and titrate with 0.05Nsilver nitrate VS,determining the endpoint potentiometrically,using a silver-based indicator electrode and a double-junction reference electrode containing 10%potassium nitrate filling solution in the outer jacket and a standard filling solution in the inner jacket,and stirring constantly (seeTitrimetry á541ñ).Calculate the percentage of sodium chloride in the specimen taken by the formula:
584.4VN/[(100–b)W],
in whichVandNrepresent the volume,in mL,and the normality,respectively,of the silver nitrate;b is the percentage ofLoss on drying,determined separately;Wis the weight,in g,of the specimen;and 584.4is the equivalence factor for sodium chloride.
SODIUM GLYCOLATE— Transfer about 500mg of it,accurately weighed,into a 100-mLbeaker,moisten thoroughly with 5mLof glacial acetic acid,followed by 5mLof water,and stir with a glass rod to ensure proper hydration (usually about 15minutes).Slowly add 50mLof acetone while stirring,then add 1g of sodium chloride,and stir for several minutes to ensure complete precipitation of the carboxymethylcellulose.Filter through a soft,open-textured paper,previously wetted with a small amount of acetone,and collect the filtrate in a 100-mLvolumetric flask.Use an additional 30mLof acetone to facilitate the transfer of the solids and to wash the filter cake,then dilute with acetone to volume,and mix.
Prepare a series of standard solutions as follows.Transfer 100mg of glycolic acid,previously dried in a desiccator at room temperature overnight and accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with water to volume,and mix.Use this solution within 30days.Transfer 1.0-mL,2.0-mL,3.0-mL,and 4.0-mLportions of the solution,respectively,to separate 100-mLvolumetric flasks;add water to each flask to make 5mL;add 5mLof glacial acetic acid;dilute with acetone to volume;and mix.
Transfer 2.0mLof the test solution and 2.0mLof each standard solution to separate 25-mLvolumetric flasks,and prepare a blank flask containing 2.0mLof a solution containing 5%each of glacial acetic acid and water in acetone.Place the uncovered flasks in a boiling water bath for 20minutes,accurately timed,to remove the acetone,remove from the bath,and cool.Add to each flask 5.0mLof 2,7-dihydroxynaphthalene TS,mix,add an additional 15mL,and again mix.Cover the mouth of each flask with a small piece of aluminum foil.Place the flasks upright in a boiling water bath for 20minutes,then 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 specimen,determine the weight (w),in mg,of glycolic acid in the specimen,and calculate the percentage of sodium glycolate in the specimen taken by the formula:
12.9w/[(100–b)W],
in which 12.9is a factor converting glycolic acid to sodium glycolate;b is the percentage ofLoss on drying,determined separately;andWis the weight,in g,of the specimen.The sum of the percentages of sodium chloride and sodium glycolate is not more than 0.5%.
Residue on ignition á281ñ: between 14.0%and 28.0%,calculated on the dried basis,about 1.0g being used for the test,using sufficient sulfuric acid to moisten the entire residue after the initial charring step,and additional sulfuric acid if an excessive amount of carbonaceous material remains after the initial complete volatilization of white fumes.Ignition temperature 600±50.
Degree of substitution— Transfer about 1g of it,accurately weighed,to a glass-stoppered,500-mLconical flask,add 300mLof sodium chloride solution (1in 10),then add 25.0mLof 0.1Nsodium hydroxide VS.Insert the stopper,and allow to stand for 5minutes with intermittent shaking.Add 5drops ofm-cresol purple TS,and from a buret add about 15mLof 0.1Nhydrochloric acid VS.Insert the stopper in the flask,and shake.If the solution is purple,add 0.1Nhydrochloric acid VSin 1-mLportions until the solution becomes yellow,shaking after each addition.Titrate with 0.1Nsodium hydroxide VSto a purple endpoint.Calculate the net number of milliequivalents,M,of base required for the neutralization of 1g of Croscarmellose Sodium,on the dried basis.
Calculate the degree of acid carboxymethyl substitution,A,by the formula:
1150M/(7102–412M–80C),
whereCis the percentage of residue on ignition of the Croscarmellose Sodium as determined in the test for Residue on ignition.
Calculate the degree of sodium carboxymethyl substitution,S,by the formula:
(162+58A)C/(7102–80C).
The degree of substitution is the sum ofA+S.It is between 0.60and 0.85,calculated on the dried basis.
Content of water-soluble material— Disperse about 10g,accurately weighed,in 800mLof water,accurately measured,and stir for 1minute every 10minutes during the first 30minutes.Allow to stand for an additional hour,or centrifuge,if necessary.Decant about 200mLof the aqueous slurry onto a rapid-filtering filter paper in a vacuum filtration funnel,apply vacuum,and collect about 150mLof the filtrate.Pour the filtrate into a tared 250-mLbeaker,weigh accurately,and calculate the weight,in g,of the filtrate,W3,by difference.Concentrate on a hot plate to a small volume,but not to dryness;dry at 105ºfor 4hours;again weigh;and calculate the weight,in g,of residueW1,by difference.Calculate the percentage of water-soluble material in the specimen,on the dried basis,taken by the formula:
100W1(800+W2)/[W2W3(1–0.01b)],
in whichW2is the weight,in g,of the specimen taken;andb is the percentageLoss on drying of the specimen taken:not more than 10.0%is found.
Settling volume— To 75mLof water in a 100-mLgraduated cylinder add 1.5g of it in 0.5-g portions,shaking vigorously after each addition.Add water to make 100mL,shake again until all of the powder is homogeneously distributed,and allow to stand for 4hours.Note the volume of the settled mass.It is between 10.0and 30.0mL.
Organic volatile impurities,Method IVá467ñ: meets the requirements.NF23
Auxiliary Information— Staff Liaison:Justin Lane,B.S.,Scientific Associate
Expert Committee:(EMC)Excipients:Monograph Content
USP28–NF23Page 2993
Pharmacopeial Forum:Volume No.30(4)Page 1439
Phone Number:1-301-816-8323