Ketoprofen Capsules

General Notices

Action and use

Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.

Definition

Ketoprofen Capsules contain Ketoprofen.

The capsules comply with the requirements stated under Capsules and with the following requirements.

Content of ketoprofen, C16H14O3

92.5 to 107.5% of the stated amount.

Identification

Shake a quantity of the contents of the capsules containing 0.5 g of Ketoprofen with 50 mL of chloroform for 5 minutes, filter, evaporate to dryness using a rotary evaporator and induce crystallisation by prolonged scratching of the side of the container with a glass rod. The infrared absorption spectrum of the crystals, Appendix II A, is concordant with the reference spectrum of ketoprofen (RS 198).

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 50 revolutions per minute.
(b) Use 900 mL of a phosphate buffer prepared by dissolving 1.46 g of potassium dihydrogen orthophosphate and 20.06 g of disodium hydrogen orthophosphate in sufficient water to produce 1000 mL, adjusting the pH to 7.5 if necessary with orthophosphoric acid, at a temperature of 37 ± 0.5°, as the medium.
procedure

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

(1) After 45 minutes withdraw a sample of the medium, filter and dilute the filtrate with sufficient of the dissolution medium to give a solution expected to contain about 0.001% w/v of Ketoprofen, at the maximum at 260 nm, Appendix II B, using the dissolution medium in the reference cell
determination of content

Calculate the total content of ketoprofen, C16H14O3, in the medium taking 662 as the value of A(1%, 1 cm) at the maximum at 260 nm.

Related substances

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

Solvent A A mixture of 40 volumes of acetonitrile and 60 volumes of water.

(1) Shake a quantity of the contents of the capsules containing 0.1 g of Ketoprofen with 100 mL of solvent A, filter and use the filtrate.
(2) Dilute 1 volume of solution (1) with 50 volumes of solvent A. Dilute 1 volume of this solution to 10 volumes with solvent A.
(3) 0.0002% w/v of ketoprofen impurity C EPCRS in solvent A.
(4) 0.0003% w/v of ketoprofen impurity A EPCRS in solvent A.
(5) Dilute 1 volume of solution (1) to 100 volumes with solvent A. To 1 volume of this solution add 1 volume of solution (4).
(6) Dilute 1 volume of solution (2) to 10 volumes with solvent A.
chromatographic conditions
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use ambient column temperature
(d) Use a detection wavelength of 233 nm.
(e) Inject 20 µL of each solution.
(g) Allow the chromatography to proceed for seven times the retention time of ketoprofen.

When the chromatograms are recorded using the prescribed conditions, the relative retentions with reference to ketoprofen (retention time about 8 minutes) are: impurity A, about 0.3 and impurity C, about 1.6.

mobile phase

2 volumes of freshly prepared phosphate buffer pH 3.5, 43 volumes of acetonitrile and 55 volumes of water.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (5), the resolution between the peaks due to ketoprofen and impurity A is at least 7.0.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to impurity C is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.2%);

the area of any peak corresponding to impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (0.3%);

the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);

the sum of the areas of all the secondary peaks other than those due to the two named impurities is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).

Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (6) (0.02%).

assay

Shake a quantity of the mixed contents of 20 capsules containing 50 mg of Ketoprofen for 10 minutes with 300 mL of methanol (75%), mix and dilute to 500 mL with methanol (75%). Allow to stand, dilute 5 mL of the supernatant liquid to 100 mL with methanol (75%) and measure the absorbance of the resulting solution at the maximum at 258 nm, Appendix II B. Calculate the content of C16H14O3 taking 662 as the value of A(1%, 1 cm) at the maximum at 258 nm.

IMPURITIES

The impurities limited by the requirements of this monograph include impurities A and C listed under Ketoprofen.