Dipipanone and Cyclizine Tablets

General Notices

Action and use

Opioid receptor agonist.

Definition

Dipipanone and Cyclizine Tablets contain, in each, 10 mg of Dipipanone Hydrochloride and 30 mg of Cyclizine Hydrochloride.

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

Content of dipipanone hydrochloride, C24H31NO,HCl,H2O

9.0 to 11.0 mg.

Content of cyclizine hydrochloride, C18H22N2,HCl

27.75 to 32.25 mg.

Identification

A. In the Assay, the chromatogram obtained with solution (3) exhibits two peaks having the same retention times as those due to dipipanone and cyclizine in the chromatogram obtained with solution (1).
B. Shake a quantity of the powdered tablets containing 60 mg of Cyclizine Hydrochloride with 10 mL of acetone and filter, reserving the filtrate for test C. Add 10 mL of chloroform to the residue, mix with the aid of ultrasound for 2 to 3 minutes, filter and evaporate to dryness. The residue yields reaction A characteristic of chlorides, Appendix VI.
C. Evaporate the filtrate reserved in test B to dryness. The residue yields reaction A characteristic of chlorides, Appendix VI.

TEST

Related substances

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) shake a quantity of the powdered tablets containing 30 mg of Cyclizine Hydrochloride with 50 mL of a mixture of equal volumes of methanol and dichloromethane, filter, evaporate the filtrate to dryness and dissolve the residue in 3 mL of the same solvent mixture. For solution (2) dilute 1 volume of solution (1) to 200 volumes with methanol. Solution (3) contains 0.0050% w/v of N-methylpiperazine in methanol. Solution (4) contains 0.10% w/v of each of cyclizine hydrochloride BPCRS and 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) (0.5%). 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.

Assay

Weigh and finely powder 20 tablets. Dissolve 0.5 g of chlorcyclizine hydrochloride BPCRS (internal standard) in sufficient dichloromethane to produce 100 mL (solution A). Carry out the method for gas chromatography, Appendix III B, using the following solutions. For solution (1) add 25 mL of solution A to 0.15 g of cyclizine hydrochloride BPCRS and 50 mg of dipipanone hydrochloride BPCRS and dilute to 50 mL with dichloromethane. For solution (2) add 40 mL of dichloromethane to a quantity of the powdered tablets containing 50 mg of Dipipanone Hydrochloride and mix with the aid of ultrasound for 20 minutes; dilute to 50 mL with dichloromethane and filter. Prepare solution (3) in the same manner as solution (2) but add 25 mL of solution A and 15 mL of dichloromethane in place of the 40 mL of dichloromethane.

The chromatographic procedure may be carried out using a glass column (1.5 m × 4 mm) packed with acid-washed, silanised diatomaceous support (80 to 100 mesh) coated with 3% w/w of silicone grease (Apiezon L is suitable) and 5% w/w of potassium hydroxide and maintained at 250°. In the chromatogram obtained with solution (2) the peaks, in order of emergence, are due to cyclizine, chlorcyclizine and dipipanone.

Calculate the content of C24H31NO,HCl,H2O using the declared content of C24H31NO,HCl,H2O in dipipanone hydrochloride BPCRS and the content of C18H22N2,HCl using the declared content of C18H22N2,HCl in cyclizine hydrochloride BPCRS.