Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Cyclo-oxygenase inhibitor; pyrazolone analgesic.
DEFINITION
Phenylbutazone Tablets contain Phenylbutazone. They are coated.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of phenylbutazone, C19H20N2O2
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Extract a quantity of the powdered tablets containing 0.2 g of Phenylbutazone with 40 mL of warm acetone, filter and evaporate the filtrate to dryness. The residue complies with the following tests.
A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of phenylbutazone (RSV 35).
B. To 0.1 g of the residue add 1 mL of glacial acetic acid and 2 mL of hydrochloric acid and heat on a water bath for 30 minutes. Cool, add 10 mL of water and filter. Add to the filtrate 3 mL of 0.1M sodium nitrite; a yellow colour is produced. Add 1 mL of this solution to 5 mL of 2-naphthol solution; a brownish red precipitate is produced which dissolves on the addition of ethanol (96%) yielding a red solution.
TESTS
Dissolution
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 1, rotating the basket at 100 revolutions per minute.
(b) Use 900 mL of a 0.68% w/v solution of potassium dihydrogen orthophosphate adjusted to pH 7.5 with 1M sodium hydroxide, at a temperature of 37°, as the medium.
PROCEDURE
After 45 minutes withdraw a 10 mL sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary, at the maximum at 264 nm, Appendix II B using the dissolution medium in the reference cell.
DETERMINATION OF CONTENT
Calculate the total content of phenylbutazone, C19H20N2O2, in the medium taking 653 as the value of A(1%, 1 cm) at the maximum at 264 nm.
Related substances
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 0.1 g of Phenylbutazone with 3 mL of chloroform containing 0.02% w/v of butylated hydroxytoluene, centrifuge and use the supernatant liquid.
(2) Dilute 1 volume of solution (1) with sufficient of the same solvent mixture to produce a solution containing 0.5 mg of Phenylbutazone per mL.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel GF254 (Machery Nagel plates are suitable). Prior to applying solutions (1) and (2), pre-treat the plate with the mobile phase allowing the solvent front to ascend 4 cm, remove the plate and dry it in a current of cold air.
(b) Use fresh mobile phase as described below.
(c) Without delay and in an atmosphere of carbon dioxide apply 3 µL of each solution. Expose the plate to carbon dioxide for 2 minutes.
(d) Develop the plate to 10 cm.
(e) After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm).
MOBILE PHASE
10 volumes of glacial acetic acid, 40 volumes of cyclohexane and 50 volumes of chloroform containing 0.02% v/v of
butylated hydroxytoluene.
LIMITS
Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (1.5%).
ASSAY
Weigh and powder 20 tablets. Extract a quantity of the powder containing 0.5 g of Phenylbutazone with successive 30-, 30-, 15- and 15-mL quantities of warm acetone. Filter the combined extracts, cool and titrate with 0.1M sodium hydroxide VS using bromothymol blue solution R3 as indicator and continuing the titration until the blue colour persists for at least 30 seconds. Repeat the titration without the powdered tablets; the difference between the titrations represents the amount of alkali required by the phenylbutazone. Each mL of 0.1M sodium hydroxide VS is equivalent to 30.84 mg of C19H20N2O2.
