Cyclizine Injection

Histamine H₁ receptor antagonist; antihistamine.

Cyclizine Injection is a sterile solution in Water for Injections containing 5% w/v of cyclizine lactate prepared by the interaction of Cyclizine and Lactic Acid.

The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.

4.65 to 5.25% w/v.

A clear, colourless solution.

A. To 0.5 mL add 10 mL of water followed by 5m sodium hydroxide until strongly alkaline to litmus paper. Extract with two 10 mL quantities of chloroform and reserve the aqueous layer for test B. Wash each chloroform extract with 5 mL of water, dry the combined extracts with anhydrous sodium sulfate, filter and evaporate the filtrate to dryness. Dissolve the residue in ethanol (96%) and evaporate to dryness. The infrared absorption spectrum of the final residue, Appendix II A, is concordant with the reference spectrum of cyclizine (RS 075).

B. The aqueous solution reserved in test A, after acidification with 1m sulfuric acid, yields the reaction characteristic of lactates, Appendix VI.

pH, 3.3 to 3.7, Appendix V L.

Carry out the method for thin-layer chromatography, Appendix III A, using silica gel G as the coating substance and as the mobile phase the lower layer obtained after shaking together a mixture of 2 volumes of 13.5m ammonia, 8 volumes of methanol and 90 volumes of dichloromethane and allowing the layers to separate. Apply separately to the plate 20 µL of each of the following freshly prepared solutions. For solution (1) dilute 1 volume of the injection to 5 volumes with methanol. For solution (2) dilute 1 volume of solution (1) to 200 volumes with methanol. Solution (3) contains 0.020% w/v of N-methylpiperazine in methanol. For solution (4) dilute 1 volume of solution (1) to 10 volumes with a 0.10% w/v solution of hydroxyzine hydrochloride BPCRS in methanol. After removal of the plate, allow it to dry in air and expose to iodine vapour for 10 minutes. Any spot corresponding to N-methylpiperazine in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (3) (2%). Any other secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%). The test is not valid unless the chromatogram obtained with solution (4) shows two clearly separated spots.

Dilute 5 mL to 100 mL with 1m sulfuric acid. To 20 mL of this solution add 2 g of sodium chloride, shake with two 50 mL quantities of ether, allow to separate and wash the ether with the same two 10 mL quantities of water. To the combined aqueous solution and washings add 20 mL of 5m sodium hydroxide and extract with three 50 mL quantities of ether. Combine the ether extracts and wash with two 10 mL quantities of a saturated solution of sodium chloride. Extract the ether layer with two 25 mL quantities of 0.05m sulfuric acid and then with two 10 mL quantities of water. Combine the acidic and aqueous extracts and dilute to 100 mL with water. Dilute 5 mL of this solution to 200 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,C₃H₆O₃  taking 331 as the value of A(1%, 1 cm) at the maximum at 225 nm.

The strength is stated in terms of the equivalent amount of cyclizine lactate in a suitable dose-volume.