Mebendazole Oral Suspension

Edition: BP 2025 (Ph. Eur. 11.6 update)

Action and use

Benzimidazole antihelminthic.

DEFINITION

Mebendazole Oral Suspension is a suspension of Mebendazole in a suitable vehicle.

The oral suspension complies with the requirements stated under Oral Liquids and with the following requirements.

PRODUCTION

The formulation and production of Mebendazole Oral Suspension are designed to control and minimise the conversion of the polymorphic form of Mebendazole from C to A. They ensure that, at any stage of the life cycle of the product, when tested by a suitable method the Mebendazole in the oral suspension is predominantly in the form of polymorph C. The acceptable crystalline form corresponds to mebendazole EPCRS

Content of mebendazole, C₁₆H₁₃N₃O₃

95.0 to 105.0% of the stated amount.

IDENTIFICATION

Shake a quantity of the suspension containing 50 mg of Mebendazole with 20 mL of water. Filter, retain the residue and wash with three 10-mL quantities of water and dry overnight under vacuum at room temperature. The infrared absorption spectrum of the residue, Appendix II A, at 3405 cm-1 and 1720 cm-1 is concordant with the mebendazole polymorph C (RS 503). The presence of different polymorphic forms is indicated by differences in the spectra at 3405 cm-1 and 1720 cm-1.

TESTS

Acidity

pH, 4.5 to 6.5, Appendix V L.

Related substances

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

(1) Shake a quantity of the oral suspension containing 50 mg of Mebendazole with 30 mL of formic acid and 30 mL of methanol (60%). Add sufficient methanol (60%) to produce 100 mL, filter (Acrodisc 0.45-µm GxF glass fiber PVDF is suitable), and use the filtrate.

(2) Dilute 1 volume of solution (1) to 100 volumes with methanol (60%). Dilute 1 volume of the resulting solution to 4 volumes with methanol (60%).

(3) To 5 mg of mebendazole BPCRS add 5 mL of methanol and 1 mL of 1M sodium hydroxide. Heat in a water bath at 60° for 1 hour, cool to room temperature, and adjust to pH 7 with 1M hydrochloric acid. Dilute to 100 mL with methanol and mix (generation of impurity A). To 1 volume of this solution, add 1 mL of 0.1% w/v of methyl parahydroxybenzoate in
methanol and dilute to 100 volumes of methanol (60%).

(4) 0.1% w/v of mebendazole for system suitability EPCRS in dimethylformamide.

CHROMATOGRAPHIC CONDITIONS

(a) Use a stainless steel column (15 cm × 4.6 mm) packed with base-deactivated octadecylsilyl silica gel for chromatography (5 µm) (Zorbax SB-C18 is suitable)

(b) Use gradient elution and the mobile phase described below.

(c) Use a flow rate of 1.5 mL per minute.

(d) Use a column temperature of 40°.

(e) Use an autosampler temperature of 5°.

(f) Use a detection wavelength of 250 nm.

(g) Inject 10 μL of each solution.

MOBILE PHASE

Mobile phase A 0.025% v/v of trifluoroacetic acid in water.

Mobile phase B acetonitrile.

When the chromatograms are recorded under the prescribed conditions, the relative retention times with reference to mebendazole (retention time about 17 minutes) are: methyl parahydroxybenzoate, about 0.66; impurity A, about 0.69; impurity C, about 0.74; impurity B, about 0.9; impurity D, about 1.1; impurity E, about 1.20; impurity F, about 1.23; impurity G, about 1.5.

SYSTEM SUITABILITY

The test is not valid unless:

in the chromatogram obtained with solution (3), the resolution between the peaks due to methyl parahydroxybenzoate and mebendazole impurity A is at least 2.0;

in the chromatogram obtained with solution (2), the signal-to-noise ratio of the peak due to mebendazole is at least 25.

LIMITS

Identify any peak in solution (1) corresponding to impurity G using the chromatogram obtained with solution (4) and multiply the area of this peak by a correction factor of 1.4.

In the chromatogram obtained with solution (1):

the area of any peak corresponding to impurity G is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);

the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.25%);

the sum of the areas of all secondary peaks is not greater than 4 times the area of the principal peak in the chromatogram obtained with solution (2) (1.0%).

Disregard any peak due to methyl parahydroxybenzoate and any peak with an area less than 0.4 times the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).

ASSAY

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

(1) Shake a weighed quantity of the oral suspension containing 50 mg of Mebendazole with 30 mL of formic acid and 30 mL of methanol (60%). Add sufficient methanol (60%) to produce 100 mL. Dilute 1 volume of the resulting solution to 5 volumes with methanol (60%). Filter (Acrodisc 0.45-µm GxF glass fiber PVDF is suitable) and use the filtrate.

(2) 0.01% w/v of mebendazole BPCRS in dimethylformamide.

(3) 0.01% w/v each of mebendazole for system suitability EPCRS and methyl parahydroxybenzoate in dimethylformamide.

CHROMATOGRAPHIC CONDITIONS

The chromatographic conditions described under Related substances may be used.

SYSTEM SUITABILITY

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to methyl parahydroxybenzoate and mebendazole impurity A is at least 2.0.

DETERMINATION OF CONTENT

Determine the weight per mL of the oral suspension, Appendix V G, and calculate the content of C₁₆H₁₃N₃O₃, weight in volume, using the declared content of C₁₆H₁₃N₃O₃ in mebendazole BPCRS.

IMPURITIES

The impurities limited by the requirements of this monograph include those listed under Mebendazole.