สารบัญ

Category Antibacterial (leprostatic).

Clofazimine contains not less than 98.5 per cent and not more than 101.5 per cent of C₂₇H₂₂Cl₂N₄, calculated on the dried basis.

Description Dark red crystals.

Solubility Practically insoluble in water; soluble in chloroform and in benzene; sparingly soluble in ethanol, in acetone and in ethyl acetate.

Warning
          1. It should be used with caution in patients with hepatic function impairment, gastro-intestinal problems such as abdominal pain and diarrhea.
          2. It should not be used in pregnant or nursing women unless clearly indicated since skin discoloration can occur in infants.
          3. It may cause splenic infarction, gastro-intestinal disturbances, bowel obstruction and bleeding, ichthyosis and dryness of the skin, rash, pruritus, and pigmentation of skin and conjunctiva and cornea.

Additional information The urine, skin and other tissues may be temporarily discoloured.

Packaging and storage Clofazimine shall be kept in tightly closed containers, protected from light.

Identification
          A. The infrared absorption spectrum is concordant with the spectrum obtained from Clofazimine RS (Appendix 2.1) or with the reference spectrum of Clofazimine.
          B. The principal spot in the chromatogram obtained from the Test preparation is similar in position and size to that in the chromatogram of the Standard preparation A as obtained in the test for Chromatographic purity.
          C. Dissolve 2 mg in 3 ml of acetone and add 2 drops of hydrochloric acid: an intense violet colour is produced. Add 0.5 ml of 5 M sodium hydroxide: the colour changes to orange-red.

Melting temperature 217º (Appendix 4.3).

Loss on drying Not more than 0.5 per cent w/w after drying at 105º to constant weight (Appendix 4.15).

Sulfated ash Not more than 0.1 per cent w/w (Appendix 5.3).

Chromatographic purity Carry out the test as described in the “Thin-layer Chromatography” (Appendix 3.1), using silica gel GF254 as the coating substance and a mixture of 10 volumes of dichloromethane and 1 volume of 1-propanol as the mobile phase. Immediately before use, expose the plate to ammonia vapours for 30 minutes by suspending the plate in a tank containing a shallow layer of approximately 25 ml of Ammonia solution. (Note Prevent the plate from coming into contact with the liquid.)
          Standard solutions Dissolve an accurately weighed quantity of Clofazimine RS in dichloromethane, and mix to obtain the Standard solution A having a known concentration of about 0.5 mg per ml. Dilute portions of the Standard solution A quantitatively with dichloromethane to obtain the Standard solutions B and C having known concentrations of 250 and 100 μg per ml, respectively.
          Test solution Dissolve an accurately weighed quantity of the test substance in dichloromethane to obtain a solution having a known concentration of about 50 mg per ml.
          Ammonia solution Transfer 1.0 ml of strong ammonia solution to a 100-ml volumetric flask, dilute with water to volume, and mix. (Note Use freshly prepared solution.)

          Procedure Apply separately to the plate, 5 μl of each of Test solution and Standard solutions. After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm). Compare the intensities of any secondary spots observed in the chromatogram of Test solution with those of the principal spots in the chromatograms of Standard solution: no secondary spot is larger or more intense than the principal spot obtained from Standard solution A (1.0 per cent), and the sum of the intensities of all secondary spots obtained from Test solution corresponds to not more than 2.0 per cent.

          Assay Dissolve about 300 mg of Clofazimine, accurately weighed, in 5 ml of chloroform, with the aid of heat if necessary. Add 20 ml of acetone and 5 ml of anhydrous glacial acetic acid, and titrate with 0.1 M perchloric acid VS, determining the end-point potentiometrically (Appendix 6.1). Perform a blank determination, and make any necessary correction. Each ml of 0.1 M perchloric acid is equivalent to 47.34 mg of C₂₇H₂₂Cl₂N₄.