Fenbufen Tablets

General Notices

Action and use

Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.

Definition

Fenbufen Tablets contain Fenbufen.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of fenbufen, C16H14O3

95.0 to 105.0% of the stated amount.

Identification

A. To a quantity of the powdered tablets containing 0.9 g of Fenbufen add 10 mL of acetone, triturate using a glass pestle, filter through filter paper wetted with acetone into 100 mL of petroleum spirit (boiling point, 40° to 60°), stir rapidly with a glass rod to induce crystallisation and allow to stand for 15 minutes. Filter through a fine porosity sintered-glass funnel, rinse the crystals with 25 mL of petroleum spirit (boiling point, 40° to 60°), remove the solvent under reduced pressure and dry the crystals at 105° for 15 minutes. The infrared absorption spectrum of the dried crystals, Appendix II A, is concordant with the reference spectrum of fenbufen (RS 140).
B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is the same as that of the peak in the chromatogram obtained with solution (2).

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 2, rotating the paddle at 100 revolutions per minute.
(b) Use 900 mL of a phosphate buffer prepared by dissolving 6.69 g of potassium dihydrogen orthophosphate and 1.63 g of sodium hydroxide in sufficient water to produce 1000 mL, adjusting the pH to 7.5 with 5m sodium hydroxide if necessary, at a temperature of 37°, as the medium.
procedure
(1) After 45 minutes withdraw a 10 mL sample of the medium, filter (Whatman 541 paper is suitable) and dilute 1 mL of the filtrate to 50 mL with the dissolution medium. Measure the absorbance of this solution, Appendix II B, at 285 nm using dissolution medium in the reference cell.
(2) Measure the absorbance of a suitable solution of fenbufen BPCRS prepared by dissolving 50 mg in 50 mL of methanol and diluting to volume with the dissolution medium and using dissolution medium in the reference cell.
determination of content

Calculate the total content of fenbufen, C16H14O3, in the medium from the absorbances obtained and using the declared content of C16H14O3, in fenbufen BPCRS.

Related substances

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

(1) To a quantity of the powdered tablets containing 0.25 g of Fenbufen add 20 mL of dimethylformamide, mix with the aid of ultrasound for 20 minutes, add sufficient of the initial mobile phase to produce 50 mL and filter (Whatman GF/F is suitable).
(2) Dilute 1 volume of solution (1) to 100 volumes with the initial mobile phase and further dilute 1 volume of this solution to 10 volumes with the initial mobile phase.
(3) 0.0025% w/v of fenbufen BPCRS and 0.0006% w/v of 3-(4-chlorobenzoyl)propionic acid.
chromatographic conditions
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS 2 is suitable).
(b) Use gradient elution and the mobile phases described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
mobile phase
Mobile phase A32 volumes of acetonitrile and 68 volumes of a solution consisting of 1 volume of glacial acetic acid and 55 volumes of water.
Mobile phase B45 volumes of acetonitrile and 55 volumes of a solution consisting of 1 volume of glacial acetic acid and 55 volumes of water.
system suitability

The test is not valid unless in the chromatogram obtained with solution (3) the resolution factor between the two principal peaks is at least 10.0.

limits

In the chromatogram obtained with solution (1):

the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.1%);

the sum of the areas of any such peaks is not greater than five times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) To a quantity of the powdered tablets containing 0.1 g of Fenbufen add 30 mL of methanol, mix with the aid of ultrasound for 15 minutes, add sufficient of the mobile phase to produce 100 mL, filter through a 0.45-µm filter (Whatman GF/C is suitable) and dilute 1 volume to 10 volumes with the mobile phase.
(2) Dissolve fenbufen BPCRS in methanol, add sufficient of the mobile phase to produce a 0.1% w/v solution and dilute 1 volume of this solution to 10 volumes with the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (30 cm × 3.9 mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 µm) (µBondapak C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 280 nm.
(f) Inject 20 µL of each solution.
mobile phase

1 volume of glacial acetic acid, 44 volumes of acetonitrile and 55 volumes of water.

determination of content

Calculate the content of C16H14O3 in the capsules using the declared content of C16H14O3 in fenbufen BPCRS.