Fenbufen Capsules

General Notices

Action and use

Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.

Definition

Fenbufen Capsules contain Fenbufen.

The capsules comply with the requirements stated under Capsules 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 contents of the capsules 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, using Apparatus 2. Use as the medium 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, and rotate the paddle at 100 revolutions per minute. Withdraw a sample of 10 mL 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. Measure the absorbance of a suitable solution of fenbufen BPCRS prepared by dissolving 50 mg in 50 mL of methanol and diluting to a suitable volume with the dissolution medium and using dissolution medium in the reference cell. Calculate the total content of fenbufen, C16H14O3 in the medium from the absorbances obtained and from the declared content of C16H14O3 in fenbufen BPCRS.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) add to a quantity of the contents of the capsules containing 0.25 g of fenbufen 20 mL of dimethylformamide, mix with the aid of ultrasound for 20 minutes, dilute to 50 mL with the initial mobile phase and filter (Whatman GF/F paper is suitable). For solution (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. Solution (3) contains 0.0025% w/v of fenbufen BPCRS and 0.0006% w/v of 3-(4-chlorobenzoyl)propionic acid.

The chromatographic procedure may be carried out using 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). Use as the initial mobile phase a mixture of 32 volumes of acetonitrile and 68 volumes of a solution consisting of 1 volume of glacial acetic acid and 55 volumes of water and as the final mobile phase a mixture of 45 volumes of acetonitrile and 55 volumes of a solution consisting of 1 volume of glacial acetic acid and 55 volumes of water. Maintain the initial mobile phase for 15 minutes, carry out a linear gradient elution with a flow rate of 2 mL per minute for 5 minutes and maintain the final mobile phase for 15 minutes with the same flow rate. Use a detection wavelength of 254 nm.

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.

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%) and 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

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) add to a quantity of the mixed contents of 20 capsules containing 0.1 g of fenbufen 30 mL of methanol, mix with the aid of ultrasound for 15 minutes, add sufficient of the mobile phase to produce 100 mL and dilute 1 volume of this solution to 10 volumes with the mobile phase. For solution (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.

The chromatographic procedure may be carried out using (a) a stainless steel column (30 cm × 3.9 mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 µm) (µBondapak C18 is suitable), maintained about 40°, (b) a mixture of 1 volume of glacial acetic acid, 44 volumes of acetonitrile and 55 volumes of water as the mobile phase with a flow rate of 1.5 mL per minute and (c) a detection wavelength of 280 nm.

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