This monograph is based on the corresponding, internationally-harmonized text developed by the Pharmacopoeial Discussion Group (PDG). Editorial modifications have been made in order to be in line with the style used in The International Pharmacopoeia.

Chemical name. Starch carboxymethyl ether, sodium salt. CAS Reg. No. 9063-38-1.

Description. White or almost white, fine, free-flowing powder.

Solubility. Practically insoluble in dichloromethane. It gives a translucent suspension in water R.

Category. Disintegrant.

Storage. Sodium starch glycolate should be kept in an airtight container, protected from light.

Labelling. The designation on the container of Sodium starch glycolate should state its type.

Additional information. Sodium starch glycolate is very hygroscopic.

Requirements

Definition. Sodium starch glycolate is the sodium salt of a cross-linked partly O-carboxymethylated starch. Type A contains not less than 2.8% and not more than 4.2% of Na, and Type B contains not less than 2.0% and not more than 3.4% of Na, each calculated with reference to the substance washed with ethanol (80% v/v) TS and dried as described under "Assay".

Identity tests

1. Prepare with shaking and without heating a mixture of 4.0 g of the test substance and 20 mL of carbon-dioxide-free water R. The mixture has the appearance of a gel. Add 100 mL of carbon-dioxide-free water R and shake. A suspension forms that settles after standing.

2. To an acidified solution, add iodinated potassium iodide TS. The solution becomes blue or violet.

3. Place 2.5 g of the test substance in a silica or platinum crucible and add 2 mL of sulfuric acid (~500 g/L) TS. Heat on a water bath, then cautiously raise the temperature progressively over an open flame. Ignite, preferably in a muffle furnace, at 575 °C to 625 °C. Continue heating until all black particles have disappeared. Cool, add a few drops of a sulfuric acid (~100 g/L) TS, and heat and ignite as above. Add a few drops of ammonium carbonate (158 g/L) TS, evaporate to dryness, and ignite as above. Cool, dissolve the residue in 50 mL of water R and mix. The solution yields reaction B described under 2.1 General identification tests as characteristic of sodium.

Clarity and colour of solution. Centrifuge the suspension obtained in identity test A at 2500 g for 10 minutes. Collect carefully the supernatant. The supernatant is clear, when tested as described under 1.18 Clarity and degree of opalescence of liquids and colourless, when compared with water R as described under 1.11.2 Degree of coloration of liquids, Method II.

Sodium glycolate. Carry out the test protected from light.

Prepare the following solutions:

For solution (1), place 0.20 g of the test substance in a beaker. Add 5 mL of acetic acid (~300 g/L) TS and 5 mL of water R. Stir until dissolution is complete (about 10 minutes). Add 50 mL of acetone R and 1 g of sodium chloride R. Filter through a fast filter paper impregnated with acetone R, rinse the beaker and filter with acetone R. Combine the filtrate and washings and dilute to 100.0 mL with acetone R. Allow to stand for 24 hours without shaking. Use the clear supernatant.

For solution (2), dissolve 0.310 g of glycolic acid R, previously dried in a desiccator (over about 100 g of molecular sieve R) at atmospheric pressure and at room temperature overnight, in water R and dilute to 500.0 mL with the same solvent. Place 5.0 mL of this solution in a beaker. Add 5 mL of acetic acid (~300 g/L) TS and allow to stand for about 30 minutes. Add 50 mL of acetone R and 1 g of sodium chloride R. Filter through a fast filter paper impregnated with acetone R, rinse the beaker and filter with acetone R. Combine the filtrate and washings and dilute to 100.0 mL with acetone R. Allow to stand for 24 hours without shaking. Use the clear supernatant.

Heat 2.0 mL of solution (1) on a water bath for 20 minutes. Cool to room temperature and add 20.0 mL of 2,7-dihydroxynaphthalene TS. Shake and heat in a water bath for 20 minutes. Cool under running water, transfer to a volumetric flask and dilute to 25.0 mL with sulfuric acid (~1760 g/L) TS, maintaining the flask under running water. Within 10 minutes, measure the absorbance at 540 nm as described under 1.6 Spectrophotometry in the visible and ultraviolet regions using water R as the blank. The absorbance of the solution prepared with solution (1) is not greater than that of a solution prepared at the same time and in the same manner with 2.0 mL of the solution (2) (2.0%).

Sodium chloride. Place 0.500 g in a beaker and suspend in 100 mL of water R. Carefully add 1 mL of nitric acid (~1000 g/L) TS. Titrate with silver nitrate (0.1 mol/L) VS, determining the end-point potentiometrically, using a silver-based indicator electrode and a double-junction reference electrode containing a solution of potassium nitrate (100 g/L) TS in the outer jacket and a standard filling solution in the inner jacket. Each mL of silver nitrate (0.1 mol/L) VS is equivalent to 5.844 mg of NaCl. The content of NaCl is not greater than 7.0 %.

pH value (1.13). Disperse 1.0 g in 30 mL of carbon-dioxide-free water R; pH of the suspension, 5.5 to 7.5 for Type A and 3.0 to 5.0 for Type B.

Iron. Use 10 mL of the solution prepared for identity test C. Treat the solution as described in 2.2.4 Limit test for iron, using 0.5 mL of iron standard FeTS; not more than 20 µg/g.

Loss on drying. Dry 1.000 g of the test substance at 130 °C for 1.5 hours; it loses not more than 100 mg/g.

Microbial contamination. It complies with the tests for Escherichia coli and Salmonella (3.3.2).

Assay. To remove chloride, shake about 1 g of the test substance with 20 mL of ethanol (80% v/v) TS, stir for 10 minutes and filter. Repeat the operation until the filtrate remains clear on the addition of silver nitrate (~0.1 mol/L) TS. Dry the residue at 105 °C to constant mass. To 0.700 g of the dried residue, add 80 mL of anhydrous acetic acid R and heat under a reflux condenser for 2 h. Cool the solution to room temperature. Titrate with perchloric acid (0.1 mol/L) VS, determining the end-point potentiometrically, as described under 2.6 Non-aqueous titration. Carry out a blank titration. Each mL of perchloric acid (0.1 mol/L) VS is equivalent to 2.299 mg of Na.