Niclosamide Tablets
Action and use
Antihelminthic.
DEFINITION
Niclosamide Chewable 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 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.
TESTS
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 at the same time and in the same manner, beginning at the words ‘add sufficient 1M hydrochloric
acid…’ (100 ppm).
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 through a membrane filter (pore size 0.45 μm is suitable) (solution A).
Dissolve 30 mg of 5-chlorosalicylic acid in 20 mL methanol and add sufficient water to produce 100 mL. Dilute 1 volume of this solution to 100 volumes with water (solution B).
Niclosamide Chewable Tablets
Separately add 0.1 mL of iron(III) chloride solution R1 to 10 mL of solution A and to 10 mL of solution B. Any red or violet colour produced in solution A is not more intense than that obtained in solution B (60 ppm).
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 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 200 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) (0.05%).
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.
