Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Corticosteroid.
DEFINITION
Hydrocortisone and Clioquinol Cream contains Hydrocortisone and Clioquinol, the latter in very fine powder, in a suitable basis.
The cream complies with the requirements stated under Topical Semi-solid Preparations and with the following requirements.
Content of hydrocortisone, C21H30O5
92.5 to 107.5% of the stated amount.
Content of clioquinol, C9H5ClINO
90.0 to 110.0% of the stated amount.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Disperse, by warming and shaking, a quantity of the cream containing 2.5 g of Hydrocortisone in 10 mL of ethanol (96%), cool, allow to stand at 0° for 30 minutes, filter and use the filtrate.
(2) 0.25% w/v of hydrocortisone BPCRS in ethanol (96%).
(3) Dissolve 12.5 mg of hydrocortisone BPCRS in 5 mL of solution (1).
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel G.
(b) Use the mobile phase as described below.
(c) Apply 5 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in air and spray with alkaline tetrazolium blue solution.
MOBILE PHASE
1.2 volumes of water, 8 volumes of methanol, 15 volumes of ether and 77 volumes of dichloromethane.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2). The principal spot in the chromatogram obtained with solution (3) appears as a single, compact spot.
B. In the Assay for hydrocortisone, the chromatogram obtained with solution (3) shows a peak with the same retention time as the peak due to hydrocortisone in the chromatogram obtained with solution (1).
C. Fuse a quantity of the cream containing 0.1 g of Clioquinol with anhydrous sodium carbonate, dissolve the fused mass in water and acidify with 2M nitric acid. Add silver nitrate solution; a pale yellow precipitate is produced which is insoluble in 5M ammonia. Add 5M ammonia until the solution becomes alkaline, boil gently, filter and acidify the filtrate with 2M nitric acid; a white precipitate is produced which darkens on exposure to light.
ASSAY
For hydrocortisone
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Add 30 mL of 2,2,4-trimethylpentane to a quantity of the cream containing 10 mg of Hydrocortisone and warm on a water bath until the preparation has melted. Extract the warm mixture with successive quantities of 30, 20 and 20 mL of methanol (80%), combine the aqueous methanolic layers, cool to about 20° and dilute to 100 mL with the same solvent.
(2) Dissolve 5 mg of hydrocortisone BPCRS in 5 mL of a 4% v/v solution of bromobenzene (internal standard) in methanol and dilute to 50 mL with methanol (80%).
(3) Prepare in the same manner as solution (1) but adding 10 mL of a 4% v/v solution of bromobenzene in methanol to the cooled methanolic extract.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 5 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Spherisorb ODS 1 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 242 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
methanol (65%).
DETERMINATION OF CONTENT
Calculate the content of C21H30O5 in the cream using the declared content of C21H30O5 in hydrocortisone BPCRS.
For clioquinol
To a quantity of the cream containing 25 mg of Clioquinol add 80 mL of a hot mixture of 6 volumes of water and 24 volumes of 2-methoxyethanol and heat on a water bath for 5 minutes. Cool in ice for 10 minutes, allow to warm to room temperature, dilute to 100 mL with the aqueous methoxyethanol, mix and filter. To 10 mL of the filtrate add 10 mL of 2-methoxyethanol and 2 mL of a solution prepared by dissolving 0.5 g of iron(III) chloride hexahydrate in 80 mL of 2-methoxyethanol and adding 0.1 mL of hydrochloric acid and sufficient 2-methoxyethanol to produce 100 mL. Dilute the solution to 25 mL with 2-methoxyethanol and measure the absorbance of the resulting solution at the maximum at 650 nm, Appendix II B, using in the reference cell a solution prepared by treating 10 mL of the aqueous methoxyethanol in the same manner beginning at the words ‘add 10 mL of 2-methoxyethanol…’.
Repeat the operation beginning at the words ‘add 10 mL of 2-methoxyethanol…’ using 10 mL of a solution prepared in the following manner. Dissolve 0.125 g of clioquinol BPCRS in sufficient 2-methoxyethanol to produce 50 mL, warming to effect solution; add 1 mL of water to 5 mL of the solution and add sufficient of a mixture of 6 volumes of water and 24 volumes of 2-methoxyethanol to produce 50 mL. Calculate the content of C9H5ClINO from the absorbances obtained and using the declared content of C9H5ClINO in clioquinol BPCRS.
STORAGE
Hydrocortisone and Clioquinol Cream should be protected from light.
