Clofazimine Capsules

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Clofazimine Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of clofazimine (C₂₇H₂₂Cl₂N₄).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Buffer: 4.5 mg/mL of sodium dodecyl sulfate, 1.7 mg/mL of tetrabutylammonium hydrogen sulfate, and 1.8 mg/mL of disodium hydrogen phosphate in water. Adjust with dilute phosphoric acid (about 8.5%) to a pH of 3.0 in 90% of the volume before diluting with water to volume.

Mobile phase: Acetonitrile and Buffer (65:35)

System suitability solution: 0.5 mg/mL of USP Clofazimine RS and 1.5 µg/mL of USP Clofazimine Related Compound B RS in Mobile phase

Standard solution: 0.05 mg/mL of USP Clofazimine RS in Mobile phase

Sample stock solution: Nominally 0.5 mg/mL of clofazimine in Mobile phase prepared as follows. Remove as completely as possible the contents of NLT 20 Capsules, and mix. Transfer the weighed portion of the combined contents of the Capsules, equivalent to about 500 mg of clofazimine, into a 250-mL conical flask. Add 50 mL of Mobile phase in increments, shake well, and quantitatively transfer into a 1000-mL volumetric flask. Repeat this process until transfer of all the Capsule contents is complete and make up the volume of the flask with Mobile phase. Stir at a high speed to make the solution homogenous.

Sample solution: Nominally 0.05 mg/mL of clofazimine from the Sample stock solution in Mobile phase prepared as follows. Filter 20 mL of the Sample stock solution into a beaker. Transfer 1.0 mL of the filtered solution into a 10-mL volumetric flask, and dilute to volume with Mobile phase.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 280 nm. For Identification test B, use a diode array detector in the range of 190 nm–400 nm.
• Column: 4.6-mm × 25-cm; 5-µm packing L7
• Flow rate: 1.0 mL/min
• Injection volume: 20 µL

System suitability

• Samples: System suitability solution and Standard solution
• Suitability requirements
• Resolution: NLT 2.0 between clofazimine and clofazimine related compound B peaks, System suitability solution
• Tailing factor: NMT 1.5 for the clofazimine peak, Standard solution
• Relative standard deviation: NMT 1.0% for the clofazimine peak, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of clofazimine (C₂₇H₂₂Cl₂N₄) in the portion of Capsules taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of clofazimine from the Sample solution

r_s = peak response of clofazimine from the Standard solution

C_s = concentration of USP Clofazimine RS in the Standard solution (mg/mL)

C_u = nominal concentration of clofazimine in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

Medium: Water; 500 mL

Apparatus 2: 50 rpm

Time: 15 min

Analysis: Place 1 Capsule in each vessel, and allow the Capsule to sink to the bottom of the vessel before starting the rotation of the blade. Observe the Capsules, and record the time taken for each Capsule shell to rupture.

Tolerances: The requirements are met if all of the Capsules tested rupture in NMT 15 min. If 1 or 2 of the Capsules rupture in more than 15 but NMT 30 min, repeat the test on 12 additional Capsules. NMT 2 of the total of 18 Capsules tested rupture in more than 15 min but NMT 30 min.

4.2 Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

5.1 Organic Impurities

Buffer, Mobile phase, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.5 µg/mL of USP Clofazimine RS and 5 µg/mL of USP Clofazimine Related Compound B RS in Mobile phase

Sample solution: Nominally 0.5 mg/mL of clofazimine in Mobile phase prepared as follows. Remove as completely as possible the contents of NLT 20 Capsules, and mix. Transfer the weighed portion of the combined contents of the Capsules, equivalent to about 500 mg of clofazimine, into a 250-mL conical flask. Add 50 mL of Mobile phase in increments, shake well, and quantitatively transfer into a 1000-mL volumetric flask. Repeat this process until transfer of all the Capsule contents is complete and make up the flask volume with Mobile phase. Stir at a high speed to make the solution homogenous and filter.

Suitability requirements

• Resolution: NLT 2.0 between the clofazimine and clofazimine related compound B peaks, System suitability solution
• Relative standard deviation: NMT 2.8% for the clofazimine peak, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of clofazimine related compound B in the portion of Capsules taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of clofazimine related compound B from the Sample solution

r_s = peak response of clofazimine related compound B from the Standard solution

C_s = concentration of USP Clofazimine Related Compound B RS in the Standard solution (mg/mL)

C_u = nominal concentration of clofazimine in the Sample solution (mg/mL)

Calculate the percentage of unspecified impurities in the portion of Capsules taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of impurities from the Sample solution

r_s = peak response of clofazimine from the Standard solution

C_s = concentration of USP Clofazimine RS in the Standard solution (mg/mL)

C_u = nominal concentration of clofazimine in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. Disregard any impurity peaks less than 0.05%.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

USP Reference Standards 〈11〉

• USP Clofazimine RS
• USP Clofazimine Related Compound B RS

5-(4-Chlorophenyl)-3-(isopropylimino)-N-phenyl-3,5-dihydrophenazin-2-amine.

C₂₇H₂₃ClN₄ 438.95