Miconazole Nitrate Topical Powder

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

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

DOWNLOAD PDF HERE

1 DEFINITION

Miconazole Nitrate Topical Powder contains NLT 90.0% and NMT 110.0% of the labeled amount of miconazole nitrate (C₁₈H₁₄CI₄N₂O · HNO₃).

2 IDENTIFICATION

A.

Sample: Transfer nominally 100 mg of miconazole nitrate from Topical Powder to a 50-mL beaker, disperse in 40 mL of methanol, and mix for a minimum of 5 min. Allow to settle for 5-10 min and filter into a 100-mL beaker. Evaporate on a steam bath or by a rotary evaporator to dryness. Dry the residue at 105° for 10 min.

Acceptance criteria: The IR absorption spectrum of a potassium bromide dispersion of the residue obtained from the Sample exhibits maxima only at the same wavelengths as that of a similar preparation of USP Miconazole Nitrate RS.

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

3 ASSAY

PROCEDURE

Buffer: 4.6 g/L of dibasic potassium phosphate tribydrate in water. Adjust with phosphoric acid to a pH of 7.5.

Solution A: Acetonitrile and Buffer (65:35)

Solution B: Acetonitrile

Solution C: Acetonitrile, water, and phosphoric acid (50:50:0.05)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (50:50)

Standard stock solution: 2 mg/mL of USP Miconazole Nitrate RS in Diluent. Sonication may be needed to aid dissolution.

Standard solution: 0.2 mg/mL of USP Miconazole Nitrate RS in Diluent from the Standard stock solution

Sample solution: Nominally 0.2 mg/mL of miconazole nitrate in Diluent prepared as follows. Transfer an appropriate amount of miconazole nitrate from a portion of the Topical Powder to a suitable volumetric flask. Add Diluent equivalent to 50% of the flask volume, shake for 30 min, and sonicate for 10 min. Dilute with Diluent to volume. Pass a portion of the solution through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm x 25-cm; 5-µm packing LZ

Column temperature: 32°

Flow rate: See Table 1.

Injection volume: 5 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of miconazole nitrate (C₁₈H₁₄CI₄N₂O · HNO₃) in the portion of Topical Powder taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of miconazole from the Sample solution 

r_S = peak response of miconazole from the Standard solution 

C_S = concentration of USP Miconazole Nitrate RS in the Standard solution (mg/mL) 

C_U = nominal concentration of miconazole nitrate in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 IMPURITIES

ORGANIC IMPURITIES

Buffer, Solution B, Solution C, Diluent, Standard stock solution, and Sample solution: Prepare as directed in the Assay.

Solution A: Acetonitrile and Buffer (35:65)

Mobile phase: See Table 2.

Table 2

System suitability solution: 0.2 mg/mL of USP Miconazole Nitrate RS from the Standard stock solution and 0.2 µg/ml. of USP Miconazole Related Compound C. RS in Diluent

Standard solution: 2 µg/mL of USP Miconazole Nitrate RS in Diluent from the Standard stock solution

Sensitivity solution: 0.1 µg/mL of USP Miconazole Nitrate RS in Diluent from the Standard solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm x 25-cm; 5-µm packing L7

Column temperature: 32°

Flow rate: See Table 2.

Injection volume: 15 µL

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements

Resolution: NLT 1.5 between miconazole related compound C and miconazole, System suitability solution

Relative standard deviation: NMT 10.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of miconazole related compound C and any individual unspecified degradation product in the portion of Topical Powder taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of miconazole related compound C or any individual unspecified degradation product from the Sample solution 

r_S = peak response of miconazole from the Standard solution 

C_S = concentration of USP Miconazole Nitrate RS in the Standard solution (µg/mL) 

C_U = nominal concentration of miconazole nitrate in the Sample solution (µg/mL) 

Acceptance criteria: See Table 3.

Table 3

5 PERFORMANCE TESTS

MINIMUM FILL (755): Meets the requirements

6 SPECIFIC TESTS

MICROBIAL ENUMERATION TESTS (61) and TESTS FOR SPECIFIED MICROORGANISMS (62): The total count does not exceed 10² cfu/g. It meets the requirements of the tests for the absence of Staphylococcus aureus and Pseudomonas aeruginosa.

7 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers. Store at controlled room temperature.

Change to read:

USP REFERENCE STANDARDS (11).

USP Miconazole Nitrate RS

USP Miconazole Related Compound C RS

2-[(2,4-Dichlorobenzyl)oxy]-2-(2,4-dichlorophenyl)ethan-1-amine ^▲hydrochloride.

C₁₅H₁₃CI₄NO · HCl        401.53 _{▲(ERR 1-Jun-2018)}