Clobetasol Propionate Cream

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

Clobetasol Propionate Cream is Clobetasol Propionate in a suitable cream base. It contains NLT 90.0% and NMT 115.0% of the labeled amount of clobetasol propionate (C₂₅H₃₂ClFO₅).

2 IDENTIFICATION

2.1 A. Thin-Layer Chromatographic Identification Test 〈201〉

Standard solution: 0.6 mg/mL of USP Clobetasol Propionate RS in chloroform

Test solution: Transfer a portion of Cream equivalent to 0.75 mg of clobetasol propionate to a 25-mL, plastic-stoppered centrifuge tube. Add 10 mL of methanol, and cap. Heat in a 60° water bath for 4 min, remove the tube from the bath, and shake vigorously. Repeat the heating and shaking. Cool to room temperature, add 3.5 mL of water, and mix. Centrifuge at 3500 rpm for 10 min. Transfer 5 mL of the supernatant to a 100-mL separator, add 1 g of sodium chloride and 10 mL of water, and mix. Extract with 5 mL of chloroform by shaking for 1 min, collect the lower layer, and evaporate with the aid of a stream of nitrogen to dryness. Dissolve the residue in 0.5 mL of chloroform.

Developing solvent system: Chloroform, acetone, and alcohol (100:10:5)

Acceptance criteria: The Rₓ value of the principal spot obtained from the Test solution corresponds to that from the Standard solution.

3 ASSAY

3.1 Procedure

Buffer: 0.05 M monobasic sodium phosphate. Adjust with 50% sodium hydroxide solution to a pH of 5.5.

Mobile phase: Acetonitrile, methanol, and Buffer (95:20:85)

Internal standard solution: 0.2 mg/mL of beclomethasone dipropionate in methanol

System suitability solution: 0.001 mg/mL of USP Clobetasol Propionate Related Compound A RS and 0.1 mg/mL of USP Clobetasol Propionate RS in Mobile phase

Standard solution: 0.04 mg/mL of USP Clobetasol Propionate RS and 0.08 mg/mL of beclomethasone dipropionate prepared as follows. Transfer 1.0 mg of USP Clobetasol Propionate RS to a 25-mL volumetric flask, add 10.0 mL of the Internal standard solution, and dilute with methanol to volume.

Sample solution: Nominally 0.04 mg/mL of clobetasol propionate. In a suitable flask, dissolve a portion of Cream equivalent to 1.0 mg of clobetasol propionate in 10.0 mL of the Internal standard solution and 15.0 mL of methanol, and shake vigorously to disperse the Cream. Centrifuge at about 3500 rpm for 10 min, and pass a portion of the supernatant through a filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

• Mode: LC
• Detector: UV 240 nm
• Column: 4.6-mm × 15-cm; packing L1
• Flow rate: 1 mL/min
• Injection size: 10 µL

System suitability

• Sample: System suitability solution
• [Note-The relative retention times for clobetasol propionate and clobetasol propionate related compound A are 1.0 and 1.1, respectively.]
• Suitability requirements
• Resolution: NLT 1.5 between clobetasol propionate and clobetasol propionate related compound A
• Column efficiency: NLT 5000 theoretical plates for the clobetasol propionate peak
• Tailing factor: NMT 2.0 for the clobetasol propionate peak
• Relative standard deviation: NMT 2.0% for the clobetasol propionate peak

Analysis

• Samples: Standard solution and Sample solution

[Note-The relative retention times for clobetasol propionate and beclomethasone dipropionate are 1.0 and 1.6, respectively.]

Calculate the percentage of clobetasol propionate (C₂₅H₃₂ClFO₅) in the portion of Cream taken:

Result = (R_u/R_s) × (C_s/C_u) × 100

R_u = ratio of the clobetasol propionate peak area to the internal standard peak area from the Sample solution

R_s = ratio of the clobetasol propionate peak area to the internal standard peak area from the Standard solution

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

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

Acceptance criteria: 90.0%–115.0%

4 PERFORMANCE TESTS

Minimum Fill 〈755〉: Meets the requirements

5 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count does not exceed 10² cfu/g. It meets the requirements of the tests for absence of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Salmonella species.

pH 〈791〉: 4.5–7.0

6 ADDITIONAL REQUIREMENTS

6.1 Packaging and Storage

Preserve in collapsible tubes or in tight containers. Store at controlled room temperature. Do not refrigerate.

6.2 USP Reference Standards 〈11〉

USP Clobetasol Propionate RS

USP Clobetasol Propionate Related Compound A RS

9α-Fluoro-11β-hydroxy-16β-methyl 3-oxo-androsta-1,4-diene-17(R)-spiro-2′-[4′-chloro-5′-ethylfuran-3′(2′H)-one].

C₂₅H₃₀ClFO₄ 448.96