Edition: BP 2025 (Ph. Eur. 11.6 update)
Diclofenac Prolonged-release Capsules
General Notices
Prolonged-release Diclofenac Capsules
Diclofenac Prolonged-release Capsules from different manufacturers, whilst complying with the requirements of the monograph, are not interchangeable unless otherwise justified and authorised.
DEFINITION
Diclofenac Prolonged-release Capsules 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 capsules comply with the requirements stated under Capsules and with the following requirements.
Content of diclofenac sodium, C14H10Cl2NNaO2
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Add 0.5 mL of glacial acetic acid and 15 mL of methanol to a quantity of the powdered capsule contents containing 0.15 g of Diclofenac Sodium and mix with the aid of ultrasound for 40 minutes. Shake gently for 1 minute, filter and collect the filtrate in 15 mL of water. Filter the precipitate (Whatman GF/C is suitable) under reduced pressure, 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. To 30 volumes of acetonitrile for chromatography add 70 volumes of water (solvent A).
(1) Add 30 mL of solvent A to a quantity of the powdered contents of the capsules containing 0.1 g of Diclofenac Sodium and mix with the aid of ultrasound for 10 minutes with occasional shaking. Cool, add sufficient solvent A to produce 50 mL and filter (Whatman GF/C is suitable).
(2) Dilute 1 volume of solution (1) to 100 volumes with solvent A and dilute 1 volume of this solution to 5 volumes with solvent A.
(3) 0.0005% w/v of diclofenac sodium BPCRS and 0.0005% w/v of diclofenac impurity A BPCRS in solvent A.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4 mm) packed with base-deactivated, end-capped octylsilyl silica gel for chromatography (5 µm) (Lichrospher RP Select B or equivalent 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 ambient column temperature.
(e) Use a detection wavelength of 230 nm.
(f) Inject 20 µL of each solution.
MOBILE PHASE
A mixture of 5 volumes of tetrahydrofuran, 30 volumes of acetonitrile and 65 volumes of 0.05M ammonium dihydrogen orthophosphate, previously adjusted to pH 5.0 using 18M ammonia.
When the chromatograms are recorded under the prescribed conditions, the retention times are about 18 minutes for diclofenac and about 26 minutes for diclofenac impurity A. Continue the chromatography for 5 times the retention time of diclofenac.
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 4.0.
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) (0.2%);
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
Dissolve 6.8 g of potassium dihydrogen orthophosphate in 1000 mL of water and adjust the pH to 6.8 with 1M sodium hydroxide (solution A). To a quantity of the mixed contents of 20 capsules containing 100 mg of Diclofenac Sodium add 10 mL of ethanol (96%) and mix with the aid of ultrasound for 20 minutes or until completely dispersed. Add 150 mL of solution A and mix with the aid of ultrasound for a further 20 minutes or until completely dispersed. Cool to room temperature, dilute to 250 mL with solution A and shake thoroughly. Filter the resulting solution and dilute 5 mL to 100 mL with solution A. Prepare a reference standard in the following manner. Dissolve 50 mg of diclofenac sodium BPCRS in 10 mL of ethanol (96%) with the aid of ultrasound for 5 minutes. Add 150 mL of solution A and mix with the aid of ultrasound for a further 5 minutes. Cool to room temperature, dilute to 250 mL with solution A and shake thoroughly. Dilute 5 mL of the resulting solution to 50 mL with solution A. Measure the absorbance, Appendix II B, of the solutions at 275 nm using in the reference cell a 0.4% v/v solution of ethanol (96%) in solution A.
Calculate the content of C14H10Cl2NNaO2 in the capsules using the absorbances at the maximum at 275 nm and the declared content of C14H10Cl2NNaO2 in diclofenac sodium BPCRS.
STORAGE
Diclofenac Prolonged-release Capsules should be protected from moisture.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed in the monograph for Diclofenac Sodium.
