Diethylcarbamazine Tablets

General Notices

Action and use

Antihelminthic.

Definition

Diethylcarbamazine Tablets contain Diethylcarbamazine Citrate.

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

Content of diethylcarbamazine citrate, C10H21N3O, C6H8O7

95.0 to 105.0% of the stated amount.

Identification

A. To a quantity of the powdered tablets containing 0.15 g of Diethylcarbamazine Citrate add 15 mL of ethanol (96%), shake for 5 minutes, filter and evaporate the filtrate to dryness. To the residue add 10 mL of 2m sodium hydroxide, filter if necessary, and extract with three 10-mL quantities of dichloromethane. Dry the combined extracts over anhydrous sodium sulfate, filter and evaporate. The infrared absorption spectrum of the oily residue, Appendix II A, is concordant with the reference spectrum of diethylcarbamazine (RS 411).
B. In the test for related substances, the chromatogram obtained with solution (1) shows a peak with the same retention time as the peak due to citric acid in the chromatogram obtained with solution (3).

TESTS

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using Apparatus 2. Use as the medium 900 mL of water and rotate the paddle at 50 revolutions per minute. Carry out the method for liquid chromatography, Appendix III D. Dissolve 31.24 g of potassium dihydrogen orthophosphate in water, add sufficient water to produce 1000 mL and mix (solution A). Solution (1) contains 0.0025% w/v of diethylcarbamazine citrate BPCRS in solution A.For solution (2) dilute 10 mL of the filtered dissolution medium with an equal volume of a 6.248% w/v solution of potassium dihydrogen orthophosphate, filter and dilute with solution A to produce a solution expected to contain about 0.0025% w/v of Diethylcarbamazine Citrate.

The chromatographic procedure described under Assay may be used.

Calculate the total content of diethylcarbamazine citrate, C10H21N3O,C6H8O7, in the medium using the declared content of C10H21N3O,C6H8O7 in diethylcarbamazine citrate BPCRS.

Dimethylpiperazine and methylpiperazine

Carry out the method for thin-layer chromatography, Appendix III A, using silica gel G as the coating substance and a mixture of 5 volumes of 13.5m ammonia, 30 volumes of butan-2-one and 65 volumes of methanol as the mobile phase. Allow the solvent front to ascend 12 cm above the line of application. Apply separately to the plate 20 µL of each of the following solutions. For solution (1) shake a quantity of the powdered tablets containing 0.50 g of Diethylcarbamazine Citrate with 20 mL of methanol and filter. For solution (2) dissolve 0.05 g of diethylcarbamazine citrate BPCRS in methanol and dilute to 2.0 mL with the same solvent. For solution (3) dissolve 10 mg of methylpiperazine in methanol and dilute to 200 mL with the same solvent. For solution (4) dissolve 10 mg of dimethylpiperazine in methanol and dilute to 200 mL with the same solvent. Dry the plate at 105° and expose to iodine vapour for 30 minutes. Any spots corresponding to methylpiperazine and dimethylpiperazine in the chromatogram obtained with solution (1) are not more intense than the spots in the chromatogram obtained with solutions (3) and (4) respectively (0.2% of each).

Related substances

Weigh and finely powder 20 tablets. Dissolve 31.24 g of potassium dihydrogen orthophosphate in water, add sufficient water to produce 1000 mL and mix (solution A). Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the powdered tablets containing 0.3 g of Diethylcarbamazine Citrate in 100 mL of solution A, centrifuge and use the clear supernatant liquid. For solution (2) dilute 1 volume of solution (1) to 100 volumes with solution A and further dilute 1 volume of the resulting solution to 10 volumes with solution A to produce a solution containing 0.0003% w/v Diethylcarbamazine Citrate. Solution (3) contains 0.2% w/v of citric acid in solution A.

The chromatographic procedure described under Assay may be used.

The area of any secondary peak in the chromatogram obtained with solution (1) is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.1%). Disregard any peak with the same retention time as citric acid in the chromatogram obtained with solution (1).

Assay

Weigh and finely powder 20 tablets. Dissolve 31.24 g of potassium dihydrogen orthophosphate in water, add sufficient water to produce 1000 mL and mix (solution A). Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) dissolve a quantity of the powdered tablets containing 25 mg of Diethylcarbamazine Citrate in 100 mL of solution A, shake and filter. Dilute 10 volumes to 50 volumes with solution A. Solution (2) contains 0.005% w/v diethylcarbamazine citrate BPCRS in solution A.

The chromatographic procedure may be carried out using (a) a stainless steel column (15 cm X 3.9 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Waters Symmetry is suitable), (b) as the mobile phase with a flow rate of 0.8 mL per minute a mixture of 100 mL of methanol and 900 mL of a solution containing 10 g of potassium dihydrogen orthophosphate in 1000 mL of water and (c) a detection wavelength of 220 nm.

Calculate the content of C10H21N3O,C6H8O7 in the tablets using the declared content of C10H21N3O,C6H8O7 in diethylcarbamazine citrate BPCRS.