Quality standards
Edition: BP 2025 (Ph. Eur. 11.6 update)
Diclofenac Prolonged-release Tablets
General Notices
Prolonged-release Diclofenac Tablets
Diclofenac Prolonged-release Tablets from different manufacturers, whilst complying with the requirements of the monograph, are not interchangeable unless otherwise justified and authorised.
Action and use
Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.
DEFINITION
Diclofenac Prolonged-release 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.
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. To a quantity of the powdered tablet cores containing 0.15 g of Diclofenac Sodium, add 0.5 mL of glacial acetic acid and 15 mL of methanol 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).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(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.
(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.
(3) 0.0005% w/v of diclofenac sodium BPCRS and 0.0005% w/v of diclofenac impurity A BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (YMC Pack-pro 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 an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
(g) Allow the chromatography to proceed for 1.5 times the retention time of diclofenac.
MOBILE PHASE
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.
When the chromatograms are recorded under the prescribed conditions, the relative retention times with reference to diclofenac (retention time about 25 minutes) are: impurity A, about 0.4 and impurity F, about 0.8.
SYSTEM SUITABILITY
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.
LIMITS
Identify the peak due to impurity A using the chromatogram obtained with solution (3) and multiply the area of the peak by a correction factor of 0.7. Identify the peak due to impurity F using the relative retention time and multiply the area of the peak by a correction factor of 0.3.
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%);
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
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 0.5 g of Diclofenac Sodium add 800 mL of methanol and mix with the aid of ultrasound. Dilute the resulting solution with the mobile phase to produce a solution containing 0.005% w/v of Diclofenac Sodium.
(2) 0.005% w/v of diclofenac sodium BPCRS in the mobile phase.
(3) 0.0005% w/v of diclofenac sodium BPCRS and 0.0005% w/v of diclofenac impurity A BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octylsilyl silica gel for chromatography (5 µm) (Zorbax C8 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 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
20 volumes of a mixture of equal volumes of a 0.1% w/v solution of phosphoric acid and a 0.16% w/v solution of sodium dihydrogen orthophosphate, adjusted to pH 2.5, and 80 volumes of methanol.
When the chromatograms are recorded under the prescribed conditions, the retention times are about 5 minutes for diclofenac and about 4 minutes for diclofenac impurity A.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks corresponding to diclofenac and diclofenac impurity A is at least 2.0.
DETERMINATION OF CONTENT
Calculate the content of C14H10Cl2NNaO2 in the tablets using the declared content of C14H10Cl2NNaO2 in diclofenac sodium BPCRS.
STORAGE
Diclofenac Prolonged-release Tablets should be protected from moisture.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Diclofenac Sodium.
