Niclosamide Tablets

General Notices

Action and use

Antihelminthic.

Definition

Niclosamide Tablets contain Niclosamide or Niclosamide Monohydrate.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of anhydrous niclosamide, C13H8Cl2N2O4

95.0 to 105.0% of the stated amount.

Identification

Heat a quantity of the powdered tablets containing 0.5 g of anhydrous niclosamide with 25 mL of hot ethanol (96%), filter while hot and evaporate the filtrate to dryness on a water bath. The residue complies with the following tests.

A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of niclosamide (RS 245). If the spectra are not concordant heat a suitable quantity of the residue at 120° for 1 hour and prepare a new spectrum.
B. Burn 20 mg by the method for oxygen-flask combustion, Appendix VIII C, using 5 mL of 2m sodium hydroxide as the absorbing liquid. The resulting solution yields a white precipitate with silver nitrate solution which is insoluble in 2m nitric acid but soluble in 5m ammonia.
C. Heat 50 mg with 5 mL of 1m hydrochloric acid and 0.1 g of zinc powder in a water bath for 10 minutes, cool and filter. To the filtrate add 0.5 mL of a 1% w/v solution of sodium nitrite and allow to stand for 10 minutes. Add 2 mL of a 2% w/v solution of ammonium sulfamate, shake, allow to stand for 10 minutes and add 2 mL of a 0.5% w/v solution of N-(1-naphthyl)ethylenediamine dihydrochloride. A deep red colour is produced.

Tests

Disintegration

The requirement for Disintegration does not apply to Niclosamide Tablets.

2-Chloro-4-nitroaniline

Boil a quantity of the powdered tablets containing 0.10 g of anhydrous niclosamide with 20 mL of methanol for 2 minutes, cool, add sufficient 1m hydrochloric acid to produce 50 mL and filter. To 10 mL of the filtrate add 0.5 mL of a 0.5% w/v solution of sodium nitrite and allow to stand for 10 minutes. Add 1 mL of a 2% w/v solution of ammonium sulfamate, shake, allow to stand for 10 minutes and add 1 mL of a 0.5% w/v solution of N-(1-naphthyl)ethylenediamine dihydrochloride. Any colour produced is not more intense than that obtained by treating 20 mL of a solution in methanol containing 10 µg of 2-chloro-4-nitroaniline in the same manner and at the same time, beginning at the words ‘add sufficient 1m hydrochloric acid…’.

5-Chlorosalicylic acid

Boil a quantity of the powdered tablets containing 0.50 g of anhydrous niclosamide with 10 mL of water for 2 minutes, cool, filter and to the filtrate add 0.2 mL of iron(iii) chloride solution R1. No red or violet colour is produced.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Shake a quantity of the powdered tablets containing the equivalent of 0.1 g of anhydrous niclosamide with 80 mL of methanol for 15 minutes, add sufficient methanol to produce 100 mL and filter.
(2) Dilute 1 volume of solution (1) to 100 volumes with acetonitrile and further dilute 1 volume of this solution to 20 volumes with acetonitrile.
(3) Dilute 1 volume of solution (2) to 10 volumes with acetonitrile.
chromatographic conditions
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 230 nm.
(f) Inject 20 µL of each solution.
(g) For solution (1), allow the chromatography to proceed for twice the retention time of the principal peak.
mobile phase

50 volumes of acetonitrile and 50 volumes of a solution containing 0.2% w/v of potassium dihydrogen orthophosphate, 0.2% w/v of tetrabutylammonium hydrogen sulfate and 0.1% w/v of disodium hydrogen orthophosphate.

limits

In the chromatogram obtained with solution (1):

the sum of the areas of any secondary peaks is not greater than 4 times the area of the principal peak in the chromatogram obtained with solution (2) (0.2%).

Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (3) (0.005%).

Assay

Weigh and powder 20 tablets. Carry out Method II for non-aqueous titration, Appendix VIII A, using a quantity of the powdered tablets containing 0.3 g of anhydrous niclosamide dissolved in 60 mL of dimethylformamide, 0.1m tetrabutylammonium hydroxide VS as titrant and determining the end point potentiometrically. Each mL of 0.1m tetrabutylammonium hydroxide VS is equivalent to 32.71 mg of C13H8Cl2N2O4.

Storage

Niclosamide Tablets should be protected from light.

Labelling

The label states that the tablets should be chewed before swallowing.

When the active ingredient is Niclosamide Monohydrate the quantity is stated in terms of the equivalent amount of anhydrous niclosamide.