Carboxymethylcellulose Sodium 12
»Carboxymethylcellulose Sodium 12is the sodium salt of a polycarboxymethyl ether of cellulose.Its degree of substitution is not less than 1.15and not more than 1.45,corresponding to a sodium (Na)content of not less than 10.4percent and not more than 12.0percent,calculated on the dried basis.
Packaging and storage— Preserve in tight containers.
Labeling— Label it to indicate the viscosity in solutions of stated concentrations of either 1%(w/w)or 2%(w/w).
Identification— Add about 1g of powdered Carboxymethylcellulose Sodium 12to 50mLof water,while stirring to produce a uniform dispersion.Continue the stirring until a clear solution is produced,and use the solution for the following tests.
A: To 1mLof the solution,diluted with an equal volume of water,in a small test tube,add 5drops of 1-naphthol TS.Incline the test tube,and carefully introduce down the side of the tube 2mLof sulfuric acid so that it forms a lower layer:a red-purple color develops at the interface.
B: To 5mLof the solution add an equal volume of barium chloride TS:a fine,white precipitate is formed.
C: Aportion of the solution responds to the tests for Sodium á191ñ.
Viscosity á911ñ— Determine the viscosity in a water solution at the concentration stated on the label.Using undried Carboxymethylcellulose Sodium 12,weigh accurately the amount which,on the dried basis,will provide 200g of solution of the stated concentration.Add the substance in small amounts to about 180mLof stirred water contained in a tared,wide-mouth bottle,continue stirring rapidly until the powder is well wetted,add sufficient water to make the mixture weigh 200g,and allow to stand,with occasional stirring,until solution is complete.Adjust the temperature to 25±0.2,and determine the viscosity,using a rotational type of viscosimeter,making certain that the system reaches equilibrium before taking the final reading.The viscosity of solutions of 2%concentration is not less than 80.0%and not more than 120.0%of that stated on the label;the viscosity of solutions of 1%concentration is not less than 75.0%and not more than 140.0%of that stated on the label.
pHá791ñ: between 6.5and 8.5,in a solution (1in 100).
Loss on drying á731ñ— Dry it at 105for 3hours:it loses not more than 10.0%of its weight.
Heavy metals— Determine as directed in the test for Heavy metalsunder Methylcellulose,using a 1.0-g specimen:the limit is 20µg per g.
Sodium chloride and Sodium glycolate—
SODIUM CHLORIDE— Weigh accurately about 5g of it into a 250-mLbeaker,add 50mLof water and 5mLof 30percent 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 electrode and a mercurous sulfate electrode having a potassium sulfate bridge,and stirring constantly.Calculate the percentage of sodium chloride in the specimen taken by the formula,
584.4VN/[(100-b)W],
in which Vand Nrepresent the volume,in mL,and the normality,respectively,of the silver nitrate,bis the percentage of Loss on drying,determined separately;Wis the weight,in g,of the specimen;and 584.4is an 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,with 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 water,dilute with water to volume,and mix.Use this solution within 30days.Transfer 1.0mL,2.0mL,3.0mL,and 4.0mLportions of the solution,respectively,to separate 100-mLvolumetric flasks,add water to each flask to make 5mL,then 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;bis the percentage of Loss on drying,determined separately;and Wis the weight,in g,of the specimen.The sum of the percentages of sodium chloride and sodium glycolate is not more than 0.5%.
Degree of substitution— Weigh accurately about 200mg of Carboxymethylcellulose Sodium 12,previously dried at 105for 3hours,and transfer to a glass-stoppered,250-mLconical flask.Add 75mLof glacial acetic acid,connect the flask to a water-cooled condenser,and reflux gently on a hot plate for 2hours.Cool,transfer the solution to a 250-mLbeaker with the aid of 50mLof glacial acetic acid,and titrate with 0.1Nperchloric acid in dioxane VSwhile stirring with a magnetic stirrer.Determine the endpoint potentiometrically with a pHmeter equipped with a standard glass electrode and a calomel electrode modified as follows.Discard the aqueous potassium chloride solution contained in the electrode,rinse and fill with the supernatant obtained by shaking thoroughly 2g each of potassium chloride and silver chloride (or silver oxide)with 100mLof methanol,then add a few crystals of potassium chloride and silver chloride (or silver oxide)to the electrode.
Record the amount,in mL,of 0.1Nperchloric acid versus mV(0-to 700-mVrange),and continue the titration to a few mLbeyond the endpoint.Plot the titration curve,and read the volume of 0.1Nperchloric acid at the inflection point.Calculate the degree of substitution in the Carboxymethylcellulose Sodium 12taken by the formula:
16.2V/(G-8.0V),
in which 16.2is one-tenth of the molecular weight of 1anhydroglucose unit;Vis the volume,in mL,of 0.1Nperchloric acid;Gis the weight,in mg,of Carboxymethylcellulose Sodium 12taken;and 8.0is one-tenth of the net increase in molecular mass of 1anhydroglucose unit for each sodium carboxymethyl group added.
Auxiliary Information— Staff Liaison:Justin Lane,B.S.,Scientific Associate
Expert Committee:(EMC)Excipients:Monograph Content
USP28–NF23Page 2978
Pharmacopeial Forum:Volume No.26(6)Page 1577
Phone Number:1-301-816-8323