Action and use
Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.
Definition
Etodolac Tablets contain Etodolac.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of etodolac C17H21NO3
95.0 to 105.0% of the stated amount.
Identification
A. Shake a quantity of the powdered tablets containing 0.5 g of etodolac with 30 mL of
hexane for 5 minutes, centrifuge, discard the clear hexane layer and add about 40 mL of
ether to the residue; shake for 5 minutes, centrifuge for 5 minutes, decant the ether layer and filter if necessary. Evaporate the solution to dryness under nitrogen and add about 5 mL of
0.1m hydrochloric acid to the residue. Warm on a water bath until the residue begins to crystallise and triturate with a glass rod to promote crystallisation. Cool the mixture in an ice bath, filter through a glass-fibre filter (Whatman GF/C is suitable) and dry the crystals at a pressure of 2 kPa at 60° for 1 hour. The
infrared absorption spectrum of the residue,
Appendix II A, is concordant with the
reference spectrum of etodolac
(RS 139).
B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the peak due to etodolac in the chromatogram obtained with solution (2).
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 1, rotating the basket at 100 revolutions per minute.
(b) Use 900 mL of phosphate buffer pH 7.5, at a temperature of 37°, as the medium.
procedure
(1) After 45 minutes withdraw a 10 mL sample of the medium and measure the
absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary, at the maximum at 278 nm,
Appendix II B using dissolution medium in the reference cell.
(2) Measure the
absorbance of a suitable solution of
etodolac BPCRS prepared by dissolving 20 mg in 100 mL of the dissolution medium, suitably diluted with the dissolution medium, using dissolution medium in the reference cell.
determination of content
Calculate the total content of etodolac, C17H21NO3 in the medium from the absorbances obtained and from the declared content of C17H21NO3 in etodolac BPCRS.
Related substances
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in acetone.
(1) Shake a quantity of the powdered tablets containing 0.2 g of etodolac with 20 mL of solvent, mix with the aid of ultrasound for 5 minutes and filter.
(2) Dilute 1 volume of solution (1) to 200 volumes.
(3) Dilute 1 volume of solution (2) to 2 volumes.
chromatographic conditions
(a) Use a
silica gel F254 precoated plate (Merck
silica gel 60 F254 plates are suitable), previously activated by heating at 105° for 1 hour. Place the plate in an unlined tank containing a solution prepared by dissolving 0.5 g of
l-ascorbic acid in 20 mL of
water and adding 80 mL of
methanol. Allow the solution to ascend 1 cm above the line of application on the plate, remove the plate and allow it to dry for at least 30 minutes.
(b) Use the mobile phase as described below.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
mobile phase
0.5 volumes of glacial acetic acid, 30 volumes of absolute ethanol and 70 volumes of toluene.
limits
Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%) and not more than one such spot is more intense than the spot in the chromatogram obtained with solution (3) (0.25%).
Etodolac acid dimer
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in acetone.
(1) Shake a quantity of the powdered tablets containing 0.6 g of Etodolac with 20 mL of solvent, mix with the aid of ultrasound for 5 minutes and filter.
chromatographic conditions
The chromatographic procedure described under Related substances may be used injecting 20 µL of each solution and using the mobile phase as described below.
mobile phase
3 volumes of glacial acetic acid, 17 volumes of 1,4-dioxan and 60 volumes of toluene.
limits
Any secondary spot in the chromatogram obtained with solution (1) corresponding to the acid dimer is not more intense than the spot in the chromatogram obtained with solution (2) (0.1%).
Total methyl analogue impurities
Carry out the method for liquid chromatography, Appendix III D, using the following solution.
(1) Shake a quantity of the powdered tablets containing 0.1 g of etodolac with 40 mL of
methanol, mix with the aid of ultrasound for 5 minutes, filter and dilute 10 mL of the filtrate to 25 mL with
water.
(2) Dilute 1 volume of a solution containing 0.025% w/v each of
etodolac 1-methyl analogue BPCRS and
etodolac 8-methyl analogue BPCRS in
methanol to 50 volumes with
water.
chromatographic conditions
(b) Use isocratic elution and the mobile phase described below. Adjust the mobile phase, if necessary, to give a retention time of 14 to 20 minutes for etodolac.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 225 nm.
(f) Inject 20 µL of each solution.
(g) For solution (1) allow the chromatography to proceed for twice the retention time of the principal peak.
mobile phase
13 volumes of acetonitrile, 19 volumes of methanol and 68 volumes of a 1.74% w/v solution of dipotassium hydrogen orthophosphate.
system suitability
The order of elution of peaks in the chromatogram obtained with solution (2) is etodolac 8-methyl analogue and etodolac 1-methyl analogue.
The test is not valid unless, in the chromatogram obtained with solution (2), the resolution factor between the two methyl analogue impurities is at least 0.75.
limits
In the chromatogram obtained with solution (1):
Calculate the percentage content of etodolac 1-methyl analogue and etodolac 8-methyl analogue in etodolac by reference to the corresponding peaks in the chromatogram obtained with solution (2). The total content is not greater than 1.0%.
Assay
Weigh and powder 20 tablets. 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 etodolac with about 70 mL of 0.1
m sodium hydroxide for 30 minutes, dilute to 100 mL with 0.1
m sodium hydroxide, mix, filter through a glass-fibre filter (Whatman GF/C is suitable) and dilute 2 mL of the resulting solution to 100 mL with the mobile phase.
(2) Dilute 2 mL of a 0.05% w/v solution of
etodolac BPCRS in 0.1
m sodium hydroxide to 100 mL with the mobile phase.
(3) Add 2 mL of a 0.05% w/v solution of
etodolac 1-methyl analogue BPCRS in 0.1
m sodium hydroxide to 2 mL of a 0.05% w/v solution of
etodolac BPCRS in 0.1
m sodium hydroxide and dilute to 100 mL with the mobile phase.
chromatographic conditions
(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 225 nm.
(f) Inject 20 µL of each solution.
mobile phase
45 volumes of acetonitrile and 55 volumes of phosphate buffer pH 4.75.
system suitability
The test is not valid unless the resolution factor between etodolac and etodolac 1-methyl analogue in the chromatogram obtained with solution (3) is at least 1.5.
determination of content
Calculate the content of C17H21NO3 using the declared content of C17H21NO3 in etodolac BPCRS.