Slow Diclofenac Tablets

Definition

 

Slow Diclofenac tablets contain diclofenac sodium. They are formulated so that the medicament is released over a period of several hours.

 

Production

 

A suitable dissolution test is carried out to demonstrate the appropriate release of diclofenac sodium. The dissolution profile reflects the in vivo performance which in turn is compatible with the dosage schedule recommended by the manufacturer.

 

With the exception of the requirements for shape, the tablets comply with the requirements stated under Tablets and with the following requirements.

 

Content of diclofenac sodium, C14H10Cl2NNaO2

 

95.0 to 105.0% of the stated amount.

 

Identification

 

Remove the coating from 10 tablets and powder the cores. Add 0.5 ml of glacial acetic acid and 15 ml of methanol  to a quantity of the powdered tablet cores containing 0.15 g of diclofenac sodium and mix with the aid of ultrasound. Shake gently for 1 minute, filter and collect the filtrate in 15 ml of water . Filter the precipitate under reduced pressure (Whatman GF/C filter paper is suitable), wash with four 5 ml quantities of water  and dry at 105 for 2 to 3 hours. The infrared absorption spectrum of the dried precipitate, Appendix II A, is concordant with the reference spectrum of diclofenac (RS 096).

 

Related substances

 

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the powdered tablets containing 50 mg of diclofenac sodium with 70 ml of the mobile phase for 30 minutes, add sufficient of the mobile phase to produce 100 ml, mix, centrifuge an aliquot and filter the supernatant liquid through a 0.45-µm filter. For solution (2) dilute 1 volume of solution (1) to 100 volumes with the mobile phase and dilute 1 volume of this solution to 5 volumes with the mobile phase. Solution (3) contains 0.0005% w/v of diclofenac sodium BPCRS and 0.0005% w/v of diclofenac impurity A EPCRS in the mobile phase.

 

The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm 4.6 mm) packed with octylsilyl silica gel for chromatography (5 µm) (end-capped Zorbax C8 is suitable), (b) as mobile phase with a flow rate of 1 ml per minute a mixture of 34 volumes of a mixture of equal volumes of a 0.1% w/v solution of orthophosphoric acid and a 0.16% w/v solution of sodium dihydrogen orthophosphate, adjusted to pH 2.5, and 66 volumes of methanol  and (c) a detection wavelength of 254 nm.

 

Inject solution (3). When the chromatograms are recorded in the prescribed conditions, the retention times are about 25 minutes for diclofenac and about 12 minutes for diclofenac impurity A. Continue the chromatography for 1.5 times the retention time of diclofenac. The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor  between the peaks corresponding to diclofenac and diclofenac impurity A is at least 6.5.

 

Inject solution (1) and solution (2). 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) (0.2%) and the sum of the areas of all the secondary peaks 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 0.25 times the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).

 

Assay

 

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake 10 tablets with 800 ml of methanol  (50%) for 30 minutes, add sufficient of the mobile phase to produce 1000 ml, mix, centrifuge an aliquot and filter the supernatant liquid through a 0.45-µm filter. Dilute the resulting solution with the mobile phase to produce a solution containing 0.005% w/v of diclofenac sodium. Solution (2) contains 0.005% w/v of diclofenac sodium BPCRS in the mobile phase. Solution (3) contains 0.0005% w/v of diclofenac sodium BPCRS and 0.0005% w/v of diclofenac impurity A EPCRS in the mobile phase.

 

The chromatographic conditions described under Related substances may be used.

 

The Assay is not valid unless, in the chromatogram obtained with solution (3), the resolution factor  between the peaks corresponding to diclofenac and diclofenac impurity A is at least 6.5.

 

Calculate the content of C14H10Cl2NNaO2 in the tablets from the chromatograms obtained and from the declared content of C14H10Cl2NNaO2 in diclofenac sodium BPCRS.

 

Storage

 

Slow Diclofenac tablets should be protected from moisture.

 

IMPURITIES

 

The impurities limited by the requirements of this monograph include those listed in the monograph for diclofenac sodium.