Edition: BP 2025 (Ph. Eur. 11.6 update)
Diclofenac Diethylamine Gel
General Notices
Action and use
Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.
DEFINITION
Diclofenac Diethylamine Gel contains Diclofenac Diethylamine in a suitable basis.
The gel complies with the requirements stated under Topical Semi-solid Preparations and with the following requirements.
Content of diclofenac diethylamine, C18H22Cl2N2O2
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) To a quantity of the gel containing 50 mg of Diclofenac Diethylamine, add 12.5 mL of methanol and mix with the aid of ultrasound for 10 minutes. Dilute to 25 mL with methanol, filter (a 0.45-µm PVDF is suitable) and use the filtrate. (2) 0.2% w/v of diclofenac diethylamine BPCRS in methanol.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating high performance silica gel (Merck silica gel 60 HPTLC plates are suitable). (b) Use the mobile phase as described below.
(c) Apply 20 µL of each solution.
(d) Develop the plate to 8 cm.
(e) After removal of the plate, dry at 105° for 30 minutes. Spray with ninhydrin solution and heat at 105° for 45 minutes.
MOBILE PHASE
1 volume of hydrochloric acid, 1 volume of water, 6 volumes of glacial acetic acid and 11 volumes of ethyl acetate.
CONFIRMATION
The two principal spots in the chromatogram obtained with solution (1) correspond in position and colour to those in the chromatogram obtained with solution (2).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the gel containing 50 mg of Diclofenac Diethylamine with 50 mL of acetone for 10 minutes, filter and evaporate the filtrate to dryness under reduced pressure. Dissolve the residue in 10 mL of a mixture of 40 volumes of water and 60 volumes of methanol, dilute 1 volume of this solution to 5 volumes with the mobile phase and filter through a glass fibre filter (Whatman GF/C is suitable).
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase.
(3) 0.1% w/v of diclofenac for system suitability EPCRS 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) For solution (1) allow the chromatography to proceed for 1.6 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, previously adjusted to pH 2.5 with orthophosphoric acid, and 66 volumes of methanol.
When the chromatograms are recorded under the prescribed conditions, the relative retentions 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 between the peaks due to impurity F and diclofenac is at least 4.0.
LIMITS
Identify any peaks due to impurities A and F in the chromatogram obtained with solution (1) using the chromatogram obtained with solution (3). Multiply the area of any peak corresponding to impurity A by a correction factor of 0.7 and any peak corresponding to impurity F by a correction factor of 0.3.
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than half the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the sum of the areas of any secondary peaks is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%).
Disregard any peak with an area less than 0.05 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.
(1) Shake a quantity of the gel containing 50 mg of Diclofenac Diethylamine with 50 mL of acetone for 10 minutes, filter and evaporate the filtrate to dryness under reduced pressure. Dissolve the residue in 100 mL of a mixture of 40 volumes of water and 60 volumes of methanol, dilute 1 volume of this solution to 10 volumes with the mobile phase and filter through a glass fibre filter (Whatman GF/C is suitable).
(2) 0.05% w/v of diclofenac sodium BPCRS in methanol. Dilute 1 volume of the resulting solution to 10 volumes using the mobile phase.
(3) 0.1% w/v of diclofenac sodium BPCRS and 0.1% w/v of diclofenac impurity A BPCRS in methanol. Dilute 1 volume of the resulting solution to 10 volumes using 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) (end-capped 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 orthophosphoric 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 impurity A.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to diclofenac and impurity A is at least 2.0.
DETERMINATION OF CONTENT
Calculate the content of C18H22Cl2N2O2 in the gel using the declared content of C14H10Cl2NNaO2 in diclofenac sodium BPCRS. Each mg of C14H10Cl2NNaO2in is equivalent to 1.1609 mg of C18H22Cl2N2O2.
