Monographs: Pharmaceutical substances: Diloxanidi furoas - Diloxanide furoate

Molecular formula. C₁₄H₁₁Cl₂NO₄

Relative molecular mass. 328.2

Graphic formula.

Chemical name.

2,2-Dichloro-4'-hydroxy-N-methylacetanilide 2-furoate (ester); 4-[(dichloroacetyl)methylamino]phenyl 2-furancarboxylate; 2,2-dichloro-N-(4-hydroxyphenyl)-N-methylacetamide 2-furoate; CAS Reg. No. 3736-81-0.

Description. A white or almost white, crystalline powder; odourless.

Solubility. Very slightly soluble in water; soluble in 100 parts of ethanol (~750 g/l) TS and in 130 parts of ether R.

Category. Antiamoebic drug.

Storage. Diloxanide furoate should be kept in a well-closed container, protected from light.

Requirements

Definition. Diloxanide furoate contains not less than 98.0% and not more than 102.0% of C₁₄H₁₁Cl₂NO₄, calculated with reference to the dried substance.

Identity tests

• Either test A alone or tests B and C may be applied.

A. Carry out the examination as described under 1.7 Spectrophotometry in the infrared region. The infrared absorption spectrum is concordant with the spectrum obtained from diloxanide furoate RS or with the reference spectrum of diloxanide furoate.

B. The absorption spectrum of a 7.0 μg/ml solution in ethanol (~750 g/l) TS, when observed between 240 nm and 350 nm, exhibits a maximum at about 258 nm; the absorbance of a 1-cm layer at this wavelength is about 0.49.

C. Carry out the combustion as described under 2.4 Oxygen flask method, using 20 mg of the test substance and 10 ml of sodium hydroxide (1 mol/l) VS as the absorbing liquid. When the process is complete, acidify with nitric acid (~130 g/l) TS; the solution yields reaction A, described under 2.1 General identification tests as characteristic of chlorides.

Melting range. 114-116 °C.

Sulfated ash. Not more than 1.0 mg/g.

Loss on drying. Dry to constant weight at 105°C; it loses not more than 5.0 mg/g.

Free acidity. Shake 3.0 g with 50 ml of carbon-dioxide-free water R, filter and wash the residue with 3 quantities, each of 20 ml of carbon-dioxide-free water R. Titrate the combined filtrate and washings with sodium hydroxide (0.1 mol/l) VS, phenolphthalein/ethanol TS being used as indicator; not more than 1.3 ml is required.

Related substances. Carry out the test as described under 1.14.1 Thin-layer chromatography, using silica gel R2 as the coating substance and a mixture of 24 volumes of dichloromethane R and 1 volume of methanol R as the mobile phase. Apply separately to the plate 5 μl of each of 2 solutions in chloroform R containing (A) 0.10 g of the test substance per ml and (B) 2.5 mg of the test substance per ml. After removing the plate from the chromatographic chamber, allow it to dry in air and examine the chromatogram in ultraviolet light (254 nm). Any spot obtained with solution A, other than the principal spot, is not more intense than that obtained with solution B.

Assay. Dissolve about 0.3 g, accurately weighed, in 50 ml of anhydrous pyridine R and titrate with tetrabutylammonium hydroxide (0.1 mol/l) VS determining the end-point potentiometrically as described under 2.6 Non-aqueous titration, Method B. Each ml of tetrabutylammonium hydroxide (0.1 mol/l) VS is equivalent to 32.82 mg of C₁₄H₁₁Cl₂NO₄.