Cyclizine Tablets

General Notices

Action and use

Histamine H₁ receptor antagonist; antihistamine.

Definition

Cyclizine Tablets contain Cyclizine Hydrochloride.

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

Content of cyclizine hydrochloride, C₁₈H₂₂N₂,HCl

95.0 to 105.0% of the stated amount.

Identification

A. Extract a quantity of the powdered tablets containing 0.1 g of Cyclizine Hydrochloride with 10 mL of ethanol (96%), filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of Cyclizine Hydrochloride (RS 076).

B. Extract a quantity of the powdered tablets containing 0.5 g of Cyclizine Hydrochloride with 20 mL of water and filter. The filtrate yields reaction A characteristic of chlorides, Appendix VI.

TESTS

Related substances

Carry out the method for gas chromatography, Appendix III B, using the following solutions prepared immediately before use.

(1) Triturate a quantity of the powdered tablets containing 0.20 g of Cyclizine Hydrochloride with 8 mL of methanol, add 2 mL of 1m sodium hydroxide and filter. Dilute 1 volume of the resulting solution to 4 volumes with methanol.

(2) Dilute 1 volume of solution (1) to 100 volumes with methanol and dilute 1 volume of the resulting solution to 5 volumes with methanol.

(3) 0.0025% w/v of cyclizine hydrochloride BPCRS, 0.0025% w/v of 1-methylpiperazine BPCRS (impurity A) and 0.0025% w/v of diphenylmethanol BPCRS (impurity B) in methanol.

chromatographic conditions

(a) Use a fused silica column (25 m × 0.33 mm) coated with a 0.5-µm film of poly(dimethyl)(diphenyl)siloxane (HP-5 is suitable).

(b) Use helium as the carrier gas with a constant flow rate of 1 mL per minute.

(d) Use a split injection ratio of 1:25.

(e) Use a flame ionisation detector at 290°.

(f) Inject 1 µL of each solution.

(g) The peaks elute in the order: methanol, 1-methylpiperazine, diphenylmethanol, cyclizine.

system suitability

Inject solution (3) six times. The relative standard deviation of each of the areas of the three principal peaks is not more than 5.0%.

The test is not valid unless in the chromatogram obtained with solution (3);

the peak-to-valley ratio between methanol and 1-methylpiperazine is at least 50;

the resolution factor between diphenylmethanol and cyclizine is at least 18.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to 1-methylpiperazine (impurity A) is not greater than the peak corresponding to 1-methylpiperazine in solution (3) (0.5%);

the area of any peak corresponding to diphenylmethanol (impurity B) is not greater than the peak corresponding to diphenylmethanol in solution (3) (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) (0.2%);

the sum of the areas of all secondary peaks is not greater than 5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.0%).

Disregard any peak with an area less than 0.5 times that of the peak due to cyclizine in the chromatogram obtained with solution (2) (0.1%).

Assay

Weigh and powder 20 tablets. Shake a quantity of the powder containing 0.125 g of Cyclizine Hydrochloride with 400 mL of 0.05m sulfuric acid for 15 minutes. Add sufficient 0.05m sulfuric acid to produce 500 mL, filter, dilute 5 mL of the filtrate to 100 mL with 0.05m sulfuric acid and measure the absorbance of the resulting solution at the maximum at 225 nm, Appendix II B. Calculate the content of C₁₈H₂₂N₂,HCl taking 390 as the value of A(1%, 1 cm) at the maximum at 225 nm.