Adapalene Gel

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

Adapalene Gel contains NLT 90.0% and NMT 110.0% of the labeled amount of adapalene (C₂₈H₂₈O₃).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U (CN 1-May-2020)

Diluent: Use Mobile phase in the Assay.

Sample stock solution: Use Sample stock solution in the Assay.

Sample solution: Nominally equivalent to 0.4 μg/mL of adapalene, prepared as follows. Dilute 2.0 mL of Sample stock solution with Diluent to 100.0 mL. Pass a portion through a Teflon filter of 0.45-μm pore size and use the filtrate.

Acceptance criteria: Meets the requirements

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

3.1 Procedure

Mobile phase: Acetonitrile, tetrahydrofuran, trifluoroacetic acid, and water (43:36:0.02:21)

Standard stock solution: 0.25 mg/mL of USP Adapalene RS, prepared as follows. Transfer USP Adapalene RS to a suitable volumetric flask,add tetrahydrofuran equivalent to 1% of the final volume, and sonicate to dissolve. Dilute with Mobile phase to volume.

Standard solution: 20 μg/mL of USP Adapalene RS in Mobile phase, from Standard stock solution

Sample stock solution: Nominally equivalent to 20 μg/mL of adapalene, prepared as follows. Transfer 2.0 g of Gel to a 100-mL volumetric flask, add 25 mL of tetrahydrofuran, and sonicate to dissolve. Add 25 mL of acetonitrile and sonicate for 20 min. Cool to room temperature and dilute with Mobile phase to volume.

Sample solution: Pass a portion of Sample stock solution through a Teflon filter of 0.45-μm pore size and use the filtrate.

3.2 Chromatographic system

Mode: LC

Detector: UV 235 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of adapalene (C₂₈H₂₈O₃) in the portion of Gel taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

4.1 Organic Impurities

Buffer: 6.8 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.5.

Solution A: Use Mobile phase in the Assay.

Solution B: Buffer and Solution A (50:50)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and tetrahydrofuran (3:2)

System suitability stock solution: 0.5 mg/mL of USP Adapalene RS, prepared as follows. Transfer USP Adapalene RS to a suitable volumetric flask, add tetrahydrofuran equivalent to 40% of the final volume, and sonicate to dissolve. Dilute with acetonitrile to volume.

System suitability solution: 0.2 mg/mL of USP Adapalene RS in Diluent, from System suitability stock solution

Standard solution: 1.0 μg/mL of USP Adapalene RS in Diluent, from System suitability solution

Sample solution: Nominally equivalent to 0.2 mg/mL of adapalene, prepared as follows. Transfer 5.0 g of Gel to a 25-mL volumetric flask.

Add 10 mL of tetrahydrofuran and sonicate to disperse for 10 min. Add 10 mL of acetonitrile and sonicate for 10 min. Cool to room temperature and dilute with acetonitrile to volume. Pass a portion through a Te on filter of 0.45-μm pore size and use the filtrate.

4.2 Chromatographic system

Mode: LC

Detector: UV 235 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 μL

4.3 System suitability

Samples: System suitability solution and Standard solution

4.4 Suitability requirements

Tailing factor: NMT 2.0, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

4.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Gel taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak area of each impurity from the Sample solution

r_s = peak area of adapalene from the Standard solution

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

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

Acceptance criteria: See Table 2. Disregard any peak less than 0.1%.

Table 2

^a Methyl 6-bromo-2-naphthoate.

^b This process impurity is controlled in the drug substance monograph. It is included in the table for identification only and it is not to be reported in the total impurities.

^c Methyl 6-[3-(adamant-1-yl)-4-methoxyphenyl]-2-naphthoate.

5 SPECIFIC TESTS

pH 〈791〉: 4.0–6.0

Minimum Fill 〈755〉: Meets the requirements

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count is NMT 102 cfu/g. The total yeasts and molds count is NMT 101cfu/g. It meets the requirements of the tests for the absence of Escherichia coli, Salmonella species, Staphylococcus aureus, and Pseudomonas aeruginosa species.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature and protect from freezing.

USP Reference Standards 〈11〉

USP Adapalene RS