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 2.0 percent and not more than 4.5 percent of sodium (Na), calculated on the dried basis.
Packaging and storage Preserve in tight containers. No storage requirements specified.
Labeling When the settling volume is determined, label it to indicate the settling volume value.
A: Shake 1 g of Low-Substituted Carboxymethylcellulose Sodium with 100 mL of sodium hydroxide solution (1 in 10): a suspension is produced.
B: Shake 1 g of Low-Substituted Carboxymethylcellulose Sodium with 50 mL of water. Transfer 1 mL of the mixture 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: 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 metals responds to the pyroantimonate precipitate test for Sodium 191.
pH 791 Shake 1 g of Low-Substituted Carboxymethylcellulose Sodium with 100 mL of carbon dioxide-free water, and centrifuge: the pH of the suspension is between 6.0 and 8.5.
Loss on drying 731 Dry 1.0 g of Low-Substituted Carboxymethylcellulose Sodium at 105º for 3 hours: it loses not more than 10.0% of its weight.
noteThe 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-mL graduated cylinder, transfer 20 mL of isopropyl alcohol, add 5.0 g of Low-Substituted Carboxymethylcellulose Sodium, and shake vigorously. Dilute with isopropyl alcohol to 30 mL, then with water to 50 mL, and shake vigorously. Within 15 minutes, repeat the shaking three times. Allow to stand for 4 hours, and determine the volume of the settled mass: it is between 15.0 mL and 35.0 mL.
Residue on ignition 281 Determined on 1.0 g 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 5.0 g of Low-Substituted Carboxymethylcellulose Sodium in 400 mL of water, and during the first 30 minutes, stir for 1 minute every 10 minutes. Allow to stand for 1 hour, and centrifuge, if necessary. Decant 100.0 mL of the supernatant onto a fast filter paper in a vacuum filtration funnel, apply a vacuum, and collect 75.0 mL of the filtrate. Evaporate in a tared platinum or porcelain dish, and dry at 105 for 4 hours: not more than 70% is found.
Heavy metals, Method II 231 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 [noteUse this solution in Identification test D.]: the limit is 20 µg per g.
Limit of sodium chloride and sodium glycolate
sodium chloride Transfer an accurately weighed quantity of about 5 g of Low-Substituted Carboxymethylcellulose Sodium to a 250-mL conical flask, add 50 mL of water and 5 mL of 30% hydrogen peroxide, and heat on a water bath for 20 minutes, stirring occasionally to ensure hydration. Cool, add 100 mL of water and 10 mL of nitric acid, and titrate while stirring constantly with 0.05 N silver 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)Win which 584.4 is the equivalence factor for sodium chloride; V is the volume, in mL, of silver nitrate; N is the normality of silver nitrate; b is the percentage obtained from the test for Loss on drying, determined separately; and W is the weight, in g, of the Low-Substituted Carboxymethylcellulose Sodium taken.
Test solution Transfer an accurately weighed quantity of about 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 minutes). 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 filter paper, previously wetted with a small amount of acetone, and collect the filtrate in a 100-mL volumetric 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 24 hours without shaking, and use the clear supernatant.
Standard stock solution Transfer 100 mg of glycolic acid, previously dried overnight in a vacuum desiccator over phosphorus pentoxide and accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with water to volume, and mix.
Standard solutions Into four identical 100-mL volumetric flasks, transfer 0.5-mL, 1.0-mL, 1.5-mL, and 2.0-mL portions of the Standard stock solution, respectively. To each flask, add water to make 5 mL, add 5 mL of 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 2.0 mL of the Test solution and 2.0 mL of each Standard solution to separate 25-mL volumetric 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 5.0 mL of 2,7-dihydroxynaphthalene TS, mix, add an additional 15 mL of 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 20 minutes, remove from the bath, cool, dilute with sulfuric acid to volume, and mix. Determine the absorbance of each solution at 540 nm 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 1.29 is a factor converting glycolic acid to sodium glycolate; w is the weight, in mg, of glycolic acid from the standard curve; b is the percentage obtained from the Loss on drying test, determined separately; and W is the weight, in g, of the Low-Substituted Carboxymethylcellulose Sodium taken. The sum of the percentages from the tests for Sodium chloride and Sodium glycolate is not more than 0.5%.
Content of sodium Calculate the percentage of sodium in the Low-Substituted Carboxymethylcellulose Sodium taken by the formula:
0.3238Ain which 0.3238 is a factor converting sodium sulfate to sodium; and A is the percentage obtained from the test for Residue on ignition, determined separately.