Low-Substituted Carboxymethylcellulose Sodium

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition
Issued and maintained by the United States Pharmacopeial Convention (USP)
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1 DEFINITION 

Low-Substituted Carboxymethylcellulose Sodium is the sodium salt of a partly O-(carboxymethylated) cellulose. It contains NLT 2.0% and NMT 4.5% of sodium (Na), calculated on the dried basis. 

2 IDENTIFICATION 

Add the following: 

2.1 A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy:

197A or 197K (NF 1-May-2020) 

Change to read: 

2.2 B. (NF 1-May-2020) 

Solution A: 100 mg/mL of sodium hydroxide 

Sample: 1 g 

Analysis: Shake the Sample with 100 mL of Solution A. 

Acceptance criteria: A suspension is produced. 

Change to read: 

2.3 C. (NF 1-May-2020) 

Sample: 1 g 

Analysis: Shake the Sample with 50 mL of water. Transfer 1 mL to a test tube, and add 1 mL of water and 1 mL of 1-naphthol TS. Incline the test tube, and add carefully 2 mL of sulfuric acid down the side so that it forms a lower layer. 

Acceptance criteria: A reddish-purple color develops at the interface. 

Delete the following: 

2.4 C. It meets the requirements in Impurities for Residue on Ignition. (NF 1-May-2020) 

2.5 D. Identification Tests—General 〈191〉, Chemical Identification Tests, Sodium, A 

Sample solution: To the residue obtained in the test for Residue on Ignition add 1 mL of hydrochloric acid, evaporate on a water bath, and dissolve in 20 mL of water. 

Acceptance criteria: Meets the requirements 

3 ASSAY 

3.1 Content of Sodium 

Analysis: Calculate the percentage of sodium in the portion of Low-Substituted Carboxymethylcellulose Sodium taken: 

Result = a × (M × A_r/M_r) 

a = percentage obtained from the test for Residue on Ignition, determined separately 

M = number of moles of sodium per mole of sodium sulfate, 2 

A_r = atomic weight of sodium, 22.99 

M_r = molecular weight of sodium sulfate, 142.04 

Acceptance criteria: 2.0%–4.5% on the dried basis 

4 IMPURITIES 

4.1 Residue on Ignition 〈281〉 

Sample: 1.0 g 

Analysis: Determine using a mixture of sulfuric acid and water (1:1) and an ignition temperature of 600 ± 50°. 

Acceptance criteria: 6.5%–13.5% 

4.2 Limit of Sodium Chloride and Sodium Glycolate 

Sodium chloride 

Sample: 5 g 

Titrimetric system 

(See Titrimetry 〈541〉.) 

Mode: Direct titration 

Titrant: 0.05 N silver nitrate VS 

Electrode system: Silver electrode and mercurous sulfate electrode with a potassium sulfate bridge 

Endpoint detection: Potentiometric 

Analysis: Transfer the Sample to a 250-mL conical ask. Add 50 mL of water and 5 mL of 30% Hydrogen peroxide, and heat on a water bath for 20 min, stirring occasionally to ensure hydration. Cool, and add 100 mL of water and 10 mL of nitric acid. Titrate with Titrant. Calculate the percentage of sodium chloride in the Sample: 

Result = {[(V × N × F)/W] × [100/(100 − b)]} × 100 

V = volume of Titrant (mL) 

N = normality of the Titrant (mEq/mL) 

F = equivalency factor for sodium chloride, 0.05844 g/mEq 

W = weight of the Sample (g) 

b = percentage obtained from the test for Loss on Drying, determined separately 

Sodium glycolate 

Standard stock solution: Transfer 100 mg of glycolic acid, previously dried overnight in a vacuum desiccator over phosphorus pentoxide, to a 100-mL volumetric ask, and dissolve in and dilute with water to volume. 

Standard solution A: Transfer 0.5 mL of the Standard stock solution to a 100-mL volumetric ask. Add water to make 5 mL, add 5 mL of glacial acetic acid, then dilute with acetone to volume. 

Standard solution B: Transfer 1.0 mL of the Standard stock solution to a 100-mL volumetric ask. Add water to make 5 mL, add 5 mL of glacial acetic acid, then dilute with acetone to volume. 

Standard solution C: Transfer 1.5 mL of the Standard stock solution to a 100-mL volumetric ask. Add water to make 5 mL, add 5 mL of glacial acetic acid, then dilute with acetone to volume. 

Standard solution D: Transfer 2.0 mL of the Standard stock solution to a 100-mL volumetric ask. Add water to make 5 mL, add 5 mL of glacial acetic acid, then dilute with acetone to volume. 

Sample solution: Transfer 500 mg of Low-Substituted Carboxymethylcellulose Sodium to a beaker, moisten thoroughly with 5 mL of glacial acetic acid, add 5 mL of water, and stir with a glass rod to ensure proper hydration (about 30 min). Add 80 mL of acetone while stirring, add 2 g of sodium chloride, and stir for several minutes to ensure the complete precipitation of carboxymethylcellulose. Pass through a fast lter paper, previously wetted with a small amount of acetone, and collect the ltrate in a 100-mL volumetric ask. Rinse the beaker and lter with acetone, and add the washings to the ask. Dilute the ltrate with acetone to volume, and mix. Allow to stand for 24 h without shaking, and use the clear supernatant. 

Instrumental conditions 

Mode: Vis 

Analytical wavelength: 540 nm 

Blank: Use acetone solution containing 5% of glacial acetic acid and 5% of water. 

Analysis: Transfer 2.0 mL of the Sample solution and 2.0 mL of each Standard solution to separate 25-mL volumetric asks. Place the uncovered asks in a boiling water bath for 20 min, accurately timed, to remove the acetone, then remove from the bath, and cool. Add to each ask 5.0 mL of 2,7-dihydroxynaphthalene TS, mix, add an additional 15 mL, and again mix. Cover the mouth of each ask with a small piece of aluminum foil. Place the asks upright in a boiling water bath for 20 min, then remove from the bath, cool, and dilute with sulfuric acid to volume. 

Determine the absorbances of the solutions against the Blank, and prepare a standard curve using the absorbances obtained from the solutions prepared from the Standard solutions. From the standard curve and the absorbance of the Sample solution, determine the concentration, in mg/mL, of glycolic acid in the Sample solution, and calculate the percentage of sodium glycolate in the sample taken: 

Result = {[(C × V)/(W × F)] × (M_r1/M_r2) × [100/(100 − b)]} × 100

C = concentration of glycolic acid in the sample, determined from the standard curve (mg/mL) 

V = volume of Sample solution (mL) 

W = weight of sample (g) 

F = unit conversion factor, 1000 mg/g 

M_r1 = molecular weight of sodium glycolate, 98.03 

M_r2 = molecular weight of glycolic acid, 76.05  

b = percentage obtained from the test for Loss on Drying, determined separately 

Acceptance criteria: The sum of the percentages obtained from the tests for Sodium chloride and Sodium glycolate is NMT 0.5%. 

5 SPECIFIC TESTS 

5.1 pH 〈791〉 

Sample: 1 g 

Analysis: Shake the Sample with 100 mL of carbon dioxide-free water, centrifuge, and test the suspension. 

Acceptance criteria: 6.0–8.5 

5.2 Loss on Drying 〈731〉 

Sample: 1.0 g 

Analysis: Dry the Sample at 105° for 3 h. 

Acceptance criteria: NMT 10.0% 

5.3 Water-Soluble Substances 

Sample: 5.0 g 

Analysis: Disperse the Sample in 400 mL of water, and during the rst 30 min, stir for 1 min every 10 min. Allow to stand for 1 h, and centrifuge, if necessary. Decant 100.0 mL of the supernatant onto a fast lter paper in a vacuum ltration funnel, apply a vacuum, and collect 75.0 mL of the ltrate. Evaporate in a tared platinum or porcelain dish, and dry at 105° for 4 h. 

Acceptance criteria: NMT 70% 

5.4 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.] 

Sample: 5.0 g 

Analysis: In a 100-mL graduated cylinder, transfer 20 mL of isopropyl alcohol, add the Sample, and shake vigorously. Dilute with isopropyl alcohol to 30 mL, then with water to 50 mL, and shake vigorously. Within 15 min, repeat the shaking three times. Allow to stand for 4 h, and determine the volume of the settled mass. 

Acceptance criteria: 15.0–35.0 mL 

6 ADDITIONAL REQUIREMENTS 

6.1 Packaging and Storage:

Preserve in tight containers. No storage requirements specied. 

6.2 Labeling:

When the settling volume is determined, label it to indicate the settling volume value. 

Add the following: 

6.3 USP Reference Standards 〈11〉 

USP Low-Substituted Carboxymethylcellulose Sodium RS (NF 1-May-2020)