Adapalene Gel

Edition: BP 2025 (Ph. Eur. 11.6 update)

General Notices

Action and use

Vitamin A analogue (retinoid); treatment of acne.

DEFINITION

Adapalene Gel contains Adapalene in a suitable basis.

The gel complies with the requirements stated under Topical Semi-solid Preparations and with the following requirements.

Content of adapalene, C₂₈H₂₈O₃

95.0 to 105.0% of the stated amount.

IDENTIFICATION

A. Carry out the method for thin-layer chromatography, Appendix III A, using the following

• To a quantity of gel containing 5 mg of Adapalene, add 10 mL of stabiliser-free tetrahydrofuran and shake to disperse. Add methanol to produce a solution containing 025% w/v of Adapalene and filter (a 0.2-µm Dynagard PP filter is suitable).
• 025% w/v of adapalene BPCRS in the mobile phase.

CHROMATOGRAPHIC CONDITIONS

• Use as the coating octadecylsilyl silica gel F254 (Merck silica gel 60 RP-18 F254 plates are suitable).
• Use the mobile phase as described
• Apply 1 µL of each
• Develop the plate to 15
• After removal of the plate dry in air and examine under ultraviolet light (254 nm).

MOBILE PHASE

18 volumes of stabiliser-free tetrahydrofuran and 82 volumes of methanol.

CONFIRMATION

The principal spot in the chromatogram obtained with solution (1) corresponds in position and colour to that in the chromatogram obtained with solution (2).

B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the principal peak in the chromatogram obtained with solution (2).

TESTS

Acidity

pH, 4.5 to 5.5, Appendix V L.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

Solvent A  2 volumes of trifluoroacetic acid and 100 volumes of water.

Solvent B 10 volumes of solvent A, 25 volumes of acetonitrile, 30 volumes of propan-2-ol and 35 volumes of stabiliser- free tetrahydrofuran.

• To a quantity of the gel containing 1 mg of Adapalene add 7 mL of stabiliser-free tetrahydrofuran and mix with the aid of ultrasound. Add 6 mL of propan-2-ol, shake, add 2 mL of solvent A and dilute to 20 mL with acetonitrile.
• Dilute 1 volume of solution (1) to 100 volumes with solvent
• 005% w/v of adapalene impurity standard BPCRS in a mixture of equal volumes of stabiliser-free tetrahydrofuran and water.
• Dilute 1 volume of solution (2) to 20 volumes with solvent

CHROMATOGRAPHIC CONDITIONS

• Use a stainless steel column (25 cm × 4 mm) packed with end-capped octadecylsily l silica gel for chromatography (5 µm) (LiChrospher 100 RP 18 is suitable).
• Use gradient elution and the mobile phase described
• Use a flow rate of 5 mL per minute.
• Use an ambient column
• Use a fluorimetric detector with the following

• Inject 10 µL of each

MOBILE PHASE

Mobile phase A 0.2 volume of trifluoroacetic acid and 100 volumes of water.

Mobile phase B 40 volumes stabiliser-free tetrahydrofuran and 60 volumes of acetonitrile.

When the chromatograms are recorded under the prescribed conditions the retention times relative to adapalene (retention time about 6.5 minutes) are: impurity A, about 0.5 and impurity D, about 3.1.

SYSTEM SUITABILITY

The test is not valid unless the chromatogram obtained with solution (3) resembles the chromatogram provided with adapalene impurity standard BPCRS.

LIMITS

In the chromatogram obtained with solution (1):

the area of any peak due to impurity A or impurity D is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.5%);

the area of any other secondary peak is not greater than 0.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);

the sum of the impurities is not greater than 1.0%.

Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.05%).

ASSAY

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

Solvent C  21 volumes of water, 36 volumes of stabiliser-free tetrahydrofuran and 43 volumes of acetonitrile.

• Disperse a quantity of the gel containing 1 mg of Adapalene in 10 mL of stabiliser-free tetrahydrofuran and shake with the aid of ultrasound for 5 minutes, dilute to 50 mL with solvent C and filter (a 0.2-µm Dynagard PP filter is suitable).
• Dilute 1 volumes of a 0.01% w/v solution of adapalene BPCRS in stabiliser-free tetrahydrofuran to 5 volumes with solvent C.

CHROMATOGRAPHIC CONDITIONS

• Use a stainless steel column (25 cm × 4 mm) with a stainless steel pre-column (4 mm × 4 mm) both packed with end- capped octadecylsily l silica gel for chromatography (5 µm) (LiChrospher 100 RP 18 is suitable).
• Use isocratic elution and the mobile phase described
• Use a flow rate of 1 mL per
• Use an ambient column
• Use a detection wavelength of 270
• Inject 25 µL of each

MOBILE PHASE

0.02 volume of trifluoroacetic acid, 21 volumes of water, 36 volumes of stabiliser-free tetrahydrofuran and 43 volumes of

acetonitrile.

SYSTEM SUITABILITY

The test is not valid unless, in the chromatogram obtained with solution (2), the column efficiency, determined on the peak due to adapalene, is at least 4500 theoretical plates per metre.

DETERMINATION OF CONTENT

Calculate the content of C28H28O3 in the gel using the declared content of C28H28O3 in adapalene BPCRS.

IMPURITIES

The impurities limited by the requirements of this monograph include impurities A and D listed under Adapalene.