Clofazimine Capsules

General Notices

Action and use

Antileprosy drug.

Definition

Clofazimine Capsules contain Clofazimine.

The capsules comply with the requirements stated under Capsules and with the following requirements.

Content of clofazimine, C27H22Cl2N4

95.0% to 105.0% of the stated amount.

Identification

A. The light absorption, Appendix II B, in the range 260 to 600 nm of the final solution obtained in the Assay, exhibits two maxima, at 289 nm and 491 nm.
B. Dissolve a quantity of the contents of the capsules containing 2 mg of Clofazimine in 3 mL of acetone and add 0.1 mL of hydrochloric acid; an intense violet colour is produced. Add 0.5 mL of 5m sodium hydroxide; the colour changes to orange-red.

TEST

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) dissolve a quantity of the contents of the capsules containing 0.5 g of Clofazimine in 100 mL of the mobile phase, filter and dilute 1 volume of this solution to 100 volumes with the mobile phase. Solution (2) contains 0.0000125% w/v of iminophenazine BPCRS in the mobile phase. Solution (3) contains 0.0005% w/v of clofazimine BPCRS and 0.0005% w/v of iminophenazine BPCRS in the mobile phase.

The chromatographic procedure may be carried out using (a) a stainless column (25 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5 µm) (Nucleosil C8 is suitable), (b) as the mobile phase with a flow rate of 1.5 mL per minute a mixture of 35 volumes of a solution prepared by dissolving 2.25 g of sodium dodecyl sulfate, 0.85 g of tetrabutylammonium hydrogen sulfate and 0.885 g of disodium hydrogen orthophosphate in 500 mL of water and adjusting the pH to 3.0 with orthophosphoric acid and 65 volumes of acetonitrile and (c) a detection wavelength of 280 nm.

Inject 20 µL of solution (3). The test is not valid unless the resolution factor between the two principal peaks is at least 2, the retention time of iminophenazine relative to that of clofazimine is about 0.7 and the column efficiency, determined on the peak due to clofazimine is at least 3000 theoretical plates.

In the chromatogram obtained with solution (1) the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.25%) and the sum of the areas of any such peaks is not greater than twice the area of the peak in the chromatogram obtained with solution (2) (0.5%).

Assay

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) add 100 mL of the mobile phase to a quantity of the mixed contents of 20 capsules containing 0.5 g of Clofazimine, filter and dilute 1 volume of this solution to 100 volumes with the mobile phase. Solution (2) contains 0.005% w/v of clofazimine BPCRS in the mobile phase. Solution (3) contains 0.0005% w/v of clofazimine BPCRS and 0.0005% w/v of iminophenazine BPCRS in the mobile phase.

The chromatographic procedure described under Related substances may be used.

Inject 20 µL of solution (3). The test is not valid unless the resolution factor between the two principal peaks is at least 2, the retention time of iminophenazine relative to that of clofazimine is about 0.7 and the column efficiency, determined on the peak due to clofazimine is at least 3000 theoretical plates.

Calculate the percentage content of C27H22Cl2N4 in the capsules using the declared content of C27H22Cl2N4 in clofazimine BPCRS.