• British Pharmacopoeia Volume III
  • Formulated Preparations: Specific Monographs

Betamethasone and Clioquinol Cream

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General Notices
Action and use

Glucocorticoid.

Definition

Betamethasone and Clioquinol Cream contains Betamethasone Valerate 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 betamethasone, C22H29FO5

90.0  to 110.0% 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 silica gel G as the coating substance and a mixture of 5  volumes of absolute ethanol, 10  volumes of acetone and 100  volumes of chloroform as the mobile phase. Apply separately to the plate 10 µl of each of the following solutions. For solution (1) disperse a quantity of the preparation being examined containing the equivalent of 0.5  mg of betamethasone in 20  ml of methanol (80%) by heating on a water bath until the methanol begins to boil. Shake vigorously, cool in ice and centrifuge. Transfer 10  ml of the supernatant liquid to a separating funnel, add 3  ml of water and 5  ml of chloroform, shake vigorously, allow the layers to separate and evaporate the chloroform layer to dryness in a current of nitrogen with gentle heating. Dissolve the residue in 1  ml of chloroform. Solution (2) contains 0.03% w/v of betamethasone valerate BPCRS in chloroform. After removal of the plate, allow it to dry in air, heat at 105° for 5  minutes and spray while hot with alkaline tetrazolium blue solution. The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).

B.  In the Assay for betamethasone the chromatogram obtained with solution (2) shows a peak with the same retention time as the peak due to betamethasone valerate in the chromatogram obtained with solution (1).

C.  In the Assay for clioquinol the chromatogram obtained with solution (2) shows a peak with the same retention time as the peak due to clioquinol in the chromatogram obtained with solution (1).

Assay
For betamethasone

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) mix 10  ml of a solution containing 0.024% w/v of betamethasone valerate BPCRS and 0.0012% w/v of betamethasone 21-valerate BPCRS in ethanol (80%) with 5  ml of a 0.072% w/v solution of beclometasone dipropionate BPCRS (internal standard) in ethanol (80%) and dilute to 50  ml with the same solvent. For solution (2) shake a quantity of the cream containing the equivalent of 2  mg of betamethasone with 100  ml of hot hexane for 2  minutes, cool, extract the mixture with 20  ml of ethanol (96%) and filter the lower, ethanolic layer through absorbent cotton previously washed with ethanol (75%). Repeat the extraction of the hexane mixture with two 10  ml quantities of ethanol (75%), filtering each extract in turn through the absorbent cotton and dilute the combined filtrates to 50  ml with ethanol (75%). Prepare solution (3) in the same manner as solution (2) but add 5  ml of a 0.072% w/v solution of the internal standard in ethanol (80%) before diluting to 50  ml.

The chromatographic procedure may be carried out using (a) a stainless steel column (10  cm × 5  mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS 1 is suitable) and maintained at 60°, (b) as the mobile phase with a flow rate of 2  ml per minute a mixture of absolute ethanol and water adjusted so that the resolution factor between the peaks due to betamethasone valerate (retention time about 5  minutes) and betamethasone 21-valerate (retention time about 7  minutes) is more than 1.0 (a mixture of 42  volumes of absolute ethanol and 58  volumes of water is usually suitable) and (c) a detection wavelength of 238  nm.

Calculate the content of C22H29FO5 in the cream using the declared content of C22H29FO5 in betamethasone valerate BPCRS and using peak areas.

For clioquinol

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) mix 5  ml of a solution containing 0.024% w/v of clioquinol BPCRS in an 80% v/v solution of 2-methoxyethanol and 1  ml of a solution containing 1% w/v of nickel(ii) chloride hexahydrate in water and dilute to 50  ml with the mobile phase. For solution (2) add 80  ml of a hot 80% v/v solution of 2-methoxyethanol to a quantity of the cream containing 30  mg of Clioquinol and heat on a water bath for 5  minutes, swirling vigorously. Cool to room temperature, dilute to 100  ml with the same solvent, mix and filter. To 5  ml of the filtrate add 1  ml of a solution containing 1% w/v of nickel(ii) chloride hexahydrate and dilute to 50  ml with the mobile phase.

The chromatographic procedure may be carried out using (a) a column (25  cm × 4.6  mm) packed with particles of silica the surface of which has been modified with chemically bonded phenyl groups (5 µm) (Spherisorb Phenyl is suitable), (b) a solution containing 0.024% w/v of nickel(ii) chloride hexahydrate in a mixture of 2  volumes of methanol, 3  volumes of acetonitrile and 5  volumes of water as the mobile phase with a flow rate of 1.5  ml per minute and (c) a detection wavelength of 273  nm.

Calculate the content of C9H5ClINO in the cream using the declared content of C9H5ClINO in clioquinol BPCRS.

Storage

Betamethasone and Clioquinol Cream should be protected from light.

Labelling

The quantity of active ingredient with respect to Betamethasone Valerate is stated in terms of the equivalent amount of betamethasone.

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