Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Used in the treatment of psoriasis.
DEFINITION
Betamethasone Valerate and Coal Tar Paste contains Betamethasone Valerate and Coal Tar in a suitable basis containing Zinc Oxide.
The paste complies with the requirements stated under Topical Semi-solid Preparations and with the following requirements. Where appropriate, the paste also complies with the requirements stated under Unlicensed Medicines.
Content of betamethasone valerate, C27H37FO6
90.0 to 110.0% of the stated amount.
Content of zinc oxide, ZnO
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) Shake a quantity of the paste containing 20 μg of Betamethasone Valerate in 10 mL of chloroform and filter (Whatman No. 1 paper is suitable). Evaporate the chloroform to dryness and extract the residue with 1 mL of a mixture of 30 volumes of methanol and 70 volumes of water.
(2) 20 μg of betamethasone valerate BPCRS in a mixture of 30 volumes of methanol and 70 volumes of water.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel GF254.
(b) Use the mobile phase as described below.
(c) Apply 20 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air and examine under ultraviolet light (254 nm). Heat the plate at 105° for 5 minutes and spray while warm with a mixture containing 1 volume of a 0.2% w/v solution of alkaline tetrazolium blue in methanol and 9 volumes of 10% w/v methanolic sodium hydroxide.
MOBILE PHASE
Mix 1 volume of ethyl acetate, 1 volume of water and 2 volumes of 1,2 –dichloroethane. Use the lower layer.
CONFIRMATION
By each method of visualisation, the principal spot in the chromatogram obtained with solution (1) corresponds in position and intensity to that in the chromatogram obtained with solution (2).
B. In the Assay for betamethasone valerate, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).
C. Heat 0.5 g of the paste gently in a porcelain dish over a small flame until the basis is completely volatilised or charred. Increase the heat until all the carbon is removed. The residue obtained is yellow when hot and white when cool.
ASSAY
For betamethasone valerate
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) 0.1% w/v of beclometasone dipropionate BPCRS (internal standard) in methanol.
(2) To a quantity of the paste containing 0.25 mg of Betamethasone Valerate add 1 mL of solution (1) and 10 mL of chloroform. Mix using a vortex mixer and filter (Whatman No. 1 filter paper is suitable), rinsing with a further 10 mL of chloroform. Evaporate the filtrate in a water bath at 40° to 50° in a current of air. Dissolve the residue in 25 mL of hexane and transfer to a separating funnel containing 20 mL of ethanolic hydrochloric acid, washing the flask with hexane. Repeat the extraction with two 10-mL quantities of ethanolic hydrochloric acid, filtering the extracts through absorbent cotton, and add sufficient ethanolic hydrochloric acid to produce 50 mL.
(3) 0.05% w/v of betamethasone valerate BPCRS in methanol.
(4) Dilute 1 volume of solution (1) and 1 volume of solution (3) to 50 volumes with ethanolic hydrochloric acid.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with base-deactivated, end-capped octadecylsilyl silica gel for chromatography (5 μm) (Hypersil BDS C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 0.8 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 240 nm.
(f) Inject 20 μL of solutions (2), (3) and (4).
MOBILE PHASE
4 volumes of water and 6 volumes of acetonitrile.
When the chromatograms are recorded under the prescribed conditions, the retention time for betamethasone valerate is about 8 minutes and the retention time for beclometasone dipropionate is about 14 minutes.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between the two principal peaks is at least 1.0.
DETERMINATION OF CONTENT
Calculate the content of C27H37FO6 in the paste using the declared content of C27H37FO6 in betamethasone valerate BPCRS.
For zinc oxide
Heat 0.5 g of the paste gently in a porcelain dish over a small flame until the basis is completely volatilised or charred. Increase the heat until all the carbon is removed. Dissolve the residue in 10 mL of 2M acetic acid and add sufficient water to produce 50 mL. To the resulting solution add 50 mg of xylenol orange triturate and sufficient hexamine to produce a violet-pink colour. Add a further 2 g of hexamine and titrate with 0.1M disodium edetate VS until the solution becomes yellow. Each mL of 0.1M disodium edetate VS is equivalent to 8.138 mg of ZnO.
STORAGE
Betamethasone Valerate and Coal Tar Paste should be stored at a temperature of 2° to 8°.
