Printed on: Tue Aug 03 2021, [Link] AM Official Status: Currently Official on 03-Aug-2021 DocId: 1_GUID-5276A322-8E95-402B-9ABA-6663CF8FA737_3_en-US

(EST)
Printed by: Le Tran Official Date: Official as of 01-Jan-2018 Document Type: NF @2021 USPC
1

5 mL, then add 5 mL of glacial acetic acid. Dilute with

Croscarmellose Sodium acetone to volume, and mix.
Portions of this monograph that are national USP text, and are Standard solution C: Transfer 3.0 mL of the Standard stock
not part of the harmonized text, are marked with symbols solution to a 100-mL volumetric flask. Add water to make
(◆ ◆) to specify this fact. 5 mL, then add 5 mL of glacial acetic acid. Dilute with
acetone to volume, and mix.
DEFINITION Standard solution D: Transfer 4.0 mL of the Standard stock
Croscarmellose Sodium is the sodium salt of a cross-linked, solution to a 100-mL volumetric flask. Add water to make
partly O-(carboxymethylated) cellulose. 5 mL, then add 5 mL of glacial acetic acid. Dilute with
acetone to volume, and mix.
IDENTIFICATION Sample solution: Transfer 500 mg to a 100-mL beaker.
• A. Mix 1 g with 100 mL of methylene blue solution (1 in Moisten thoroughly with 5 mL of glacial acetic acid,
250,000), stir the mixture, and allow it to settle. The followed by 5 mL of water, and stir with a glass rod to
Croscarmellose Sodium absorbs the methylene blue and ensure proper hydration (usually about 15 min). Slowly
settles as a blue, fibrous mass. add 50 mL of acetone while stirring, then add 1 g of
• B. Mix 1 g with 50 mL of water. Transfer 1 mL of the mixture sodium chloride, and stir for several min to ensure
to a small test tube, and add 1 mL of water and 5 drops of complete precipitation of the carboxymethylcellulose.
1-naphthol TS. Incline the test tube, and carefully add 2 mL Filter through a soft, open-textured paper, previously
of sulfuric acid down the side so that it forms a lower layer: a wetted with a small amount of acetone, and collect the
reddish-violet color develops at the interface. filtrate in a 100-mL volumetric flask. Use an additional
• ◆C. A portion of the mixture of Croscarmellose Sodium with 30 mL of acetone to facilitate the transfer of the solids and
water, prepared as directed in Identification B, imparts an to wash the filter cake, then dilute with acetone to volume,
intense yellow color to a nonluminous flame.◆ and mix.

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IMPURITIES Analysis
• RESIDUE ON IGNITION á281ñ: 14.0%–28.0%, calculated on Samples: Standard solution A, Standard solution B,
the dried basis. Use 1.0 g for the test, and use sufficient Standard solution C, Standard solution D, and Sample
sulfuric acid to moisten the entire residue after the initial solution
Transfer 2.0 mL of the Sample solution and 2.0 mL of each
charring step, and additional sulfuric acid if an excessive
amount of carbonaceous material remains after the initial
complete volatilization of white fumes.
• ◆SODIUM CHLORIDE AND SODIUM GLYCOLATE
ci Standard solution to separate 25-mL volumetric flasks,
and prepare a blank flask containing 2.0 mL of a solution
containing 5% each of glacial acetic acid and water in
Sodium chloride acetone. Place the uncovered flasks in a boiling water
Sample: 5 g of Croscarmellose Sodium bath for 20 min to remove the acetone. Remove from
ffi
Analysis: Transfer the Sample to a 250-mL beaker. Add the bath, and cool. Add to each flask 5.0 mL of
50 mL of water and 5 mL of 30% hydrogen peroxide, and 2,7-dihydroxynaphthalene TS, mix, add an additional
heat on a steam bath for 20 min, stirring occasionally to 15 mL, and again mix. Cover the mouth of each flask
ensure hydration. Cool, and add 100 mL of water and with a small piece of aluminum foil. Place the flasks
10 mL of nitric acid. Titrate with 0.05 N silver nitrate VS, upright in a boiling water bath for 20 min, then remove
determining the endpoint potentiometrically, using a from the bath, cool, dilute with sulfuric acid to volume,
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silver-based indicator electrode and a double-junction and mix.

reference electrode containing 10% potassium nitrate Determine the absorbance of each solution at 540 nm,
filling solution in the outer jacket and a standard filling with a suitable spectrophotometer, against the blank,
solution in the inner jacket, and stirring constantly (see and prepare a standard curve using the absorbances
Titrimetry á541ñ). obtained from the Standard solutions.
Calculate the percentage of sodium chloride in the Calculate the percentage of sodium glycolate in the
specimen taken: specimen taken:

Result = (F × V × N)/[(100 − b) × W] Result = (F × W1)/[(100 − b) × W2]

F = equivalence factor for sodium chloride, 584.4 F = factor converting glycolic acid to sodium
V = volume of the silver nitrate (mL) glycolate, 12.9
N = normality of the silver nitrate W1 = weight of glycolic acid in the specimen,
b = percentage of loss on drying, determined determined from the standard curve and the
separately absorbance of the Sample solution (mg)
W = weight of the specimen (g) b = percentage of loss on drying, determined
separately
Sodium glycolate W2 = weight of the specimen taken (g)
Standard stock solution: Transfer 100 mg of glycolic acid,
previously dried in a desiccator at room temperature Acceptance criteria: The sum of the percentages of
overnight, to a 100-mL volumetric flask. Dissolve in and sodium chloride and sodium glycolate is NMT 0.5%.◆
dilute with water to volume, and mix. [NOTE—Use this
SPECIFIC TESTS
solution within 30 days.]
• ◆CONTENT OF WATER-SOLUBLE MATERIAL
Standard solution A: Transfer 1.0 mL of the Standard stock
Analysis: Disperse 10 g in 800 mL of water, and stir for 1 min
solution to a 100-mL volumetric flask. Add water to make
every 10 min during the first 30 min. Allow to stand for an
5 mL, then add 5 mL of glacial acetic acid. Dilute with
additional hour, or centrifuge, if necessary. Decant 200 mL
acetone to volume, and mix.
of the aqueous slurry onto a rapid-filtering filter paper in a
Standard solution B: Transfer 2.0 mL of the Standard stock vacuum filtration funnel, apply vacuum, and collect about
solution to a 100-mL volumetric flask. Add water to make 150 mL of the filtrate. Pour the filtrate into a tared 250-mL
beaker, weigh, and calculate the weight, in g, of the filtrate,

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Printed on: Tue Aug 03 2021, [Link] AM Official Status: Currently Official on 03-Aug-2021 DocId: 1_GUID-5276A322-8E95-402B-9ABA-6663CF8FA737_3_en-US
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W3, by difference. Concentrate on a hot plate to a small Calculate the degree of sodium carboxymethyl
volume, but not to dryness; dry at 105° for 4 h; and again substitution, S:
weigh.
Calculate, in g, the weight of the residue by difference, W1. Result = [162 + (58 × A)] × C/[7102 − (80 × C)]
Calculate the percentage of water-soluble material in the
specimen, on the dried basis, taken: A = degree of acid carboxymethyl substitution, as
determined above
Result = [100 × W1 × (800 + W2)]/{W2 × W3 × [1 − (0.01 × b)]} C = percentage of residue on ignition of the
Croscarmellose Sodium as determined in the
W1 = weight of residue by difference (g) test for Residue on Ignition
W2 = weight of the specimen taken (g)
The degree of substitution is the sum of A + S.
W3 = weight of the filtrate by difference (g)
Acceptance criteria: The degree of substitution is 0.60–
b = percentage loss on drying of the specimen taken 0.85 on the dried basis.
• LOSS ON DRYING á731ñ
Acceptance criteria: NMT 10.0%◆ Analysis: Dry at 105° for 6 h.
• DEGREE OF SUBSTITUTION Acceptance criteria: NMT 10.0%
Sample: 1 g • ◆ MICROBIAL ENUMERATION TESTS á61ñ and TESTS FOR
Analysis: Transfer the Sample to a glass-stoppered, 500-mL SPECIFIED MICROORGANISMS á62ñ: The total aerobic
conical flask. Add 300 mL of sodium chloride solution (1 in microbial count does not exceed 1000 cfu/g, and the total
10), then add 25.0 mL of 0.1 N sodium hydroxide VS. Insert combined molds and yeasts count does not exceed
the stopper, and allow to stand for 5 min with intermittent 100 cfu/g. It meets the requirements of the test for
shaking. Add 5 drops of m-cresol purple TS, and from a absence of Escherichia coli.◆

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buret add 15 mL of 0.1 N hydrochloric acid VS. Insert the • PH á791ñ
stopper in the flask, and shake. If the solution is violet, add Analysis: Mix 1 g with 100 mL of water for 5 min.
0.1 N hydrochloric acid VS in 1-mL portions until the Acceptance criteria: 5.0–7.0
solution becomes yellow, shaking after each addition. • SETTLING VOLUME
Titrate with 0.1 N sodium hydroxide VS to a violet Analysis: To 75 mL of water in a 100-mL graduated cylinder,
endpoint.
Calculate the net number of milliequivalents, M, of base
required for the neutralization of 1 g of Croscarmellose
Sodium, on the dried basis.
ci add 1.5 g of it in 0.5-g portions, shaking vigorously after
each addition. Add water to make 100 mL, shake again until
all of the powder is homogeneously distributed, and allow
to stand for 4 h. Note the volume of the settled mass.
Calculate the degree of acid carboxymethyl substitution, A: Acceptance criteria: The volume of the settled mass is 10.0–
ffi
Result = 1150 × M/[7102 − (412 × M) − (80 × C)] 30.0 mL.
ADDITIONAL REQUIREMENTS
M = milliequivalents of base • PACKAGING AND STORAGE: Preserve in well-closed
C = percentage of residue on ignition of the containers. No storage requirements specified.
Croscarmellose Sodium as determined in the
test for Residue on Ignition
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