Etodolac Extended-Release Tablets
» Etodolac Extended-Release Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of etodolac (C17H21NO3).
Packaging and storage—
Preserve in well-closed containers. Store at controlled room temperature, protected from light.
Labeling—
When more than one Dissolution Test is given, the labeling states the Dissolution Test used only if Test 1 is not used.
USP Reference standards 
11
—
11—
USP Etodolac RS 
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USP Etodolac Related Compound A RS
(±)-8-Ethyl-1-methyl-1,3,4,9-tetrahydropyrano [3,4-b]-indole-1-acetic acid.
C16H19NO3 273.33
(±)-8-Ethyl-1-methyl-1,3,4,9-tetrahydropyrano [3,4-b]-indole-1-acetic acid.
C16H19NO3 273.33
Identification—
The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution 711—
711—
test 1—
Medium:
0.05 M phosphate buffer, pH 7.4; 1000 mL.
Apparatus 2:
75 rpm, with USP sinker.
Times:
3, 6, 10, and 16 hours.
Procedure—
Determine the amount of C17H21NO3 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 279 nm on filtered portions of the solution under test, suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Etodolac RS in the same Medium. Use Medium as the blank.
Tolerances—
The percentages of the labeled amount of C17H21NO3 dissolved at the times specified conform to Acceptance Table 2.
| Time (hours) |  Amount dissolved |
|---|---|
| 3 | between 15% and 40% |
| 6 | between 35% and 70% |
| 10 | between 60% and 95% |
| 16 | not less than 80% |
test 2—
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:
0.05 M phosphate buffer, pH 7.5; 1000 mL.
Apparatus 2:
100 rpm.
Times:
2, 4, 8, and 14 hours.
Procedure—
Determine the amount of C17H21NO3 dissolved by comparing the difference between the absorbances of the filtered portions of the solution under test determined at 278 nm and 245 nm with the difference between the absorbances of a Standard solution having a known concentration of USP Etodolac RS in the same Medium determined at the same wavelengths. Use Medium as the blank, and use a 0.05-cm silica cell.
Tolerances—
The percentages of the labeled amount of C17H21NO3 dissolved at the times specified conform to Acceptance Table 2.
| Time (hours) | Amount dissolved |
|---|---|
| 2 | between 10% and 35% |
| 4 | between 30% and 55% |
| 8 | between 60% and 90% |
| 14 | not less than 85% |
test 3—
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Medium:
0.05 M phosphate buffer, pH 6.8; 1000 mL.
Apparatus 2:
75 rpm.
Times:
2, 4, 8, and 14 hours.
Procedure—
Determine the amount of C17H21NO3 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 278 nm on portions of the solution under test passed through a 10-µm polyethylene filter, suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Etodolac RS in the same Medium. Use Medium as the blank, and use a 0.05-cm silica cell.
Tolerances—
The percentages of the labeled amount of C17H21NO3 dissolved at the times specified conform to Acceptance Table 2.
| Time (hours) | Amount dissolved |
|---|---|
| 2 | between 10% and 30% |
| 4 | between 30% and 50% |
| 8 | between 55% and 75% |
| 14 | not less than 80% |
test 4—
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.
Medium:
0.05 M phosphate buffer, pH 6.8; 900 mL.
Apparatus 2:
75 rpm, with a wire helix sinker.
Times:
2, 4, 8, and 18 hours.
Test solution—
Pass a portion of the solution under test through a suitable 70-µm filter.
Standard solution—
From a solution containing about 4 mg per mL of USP Etodolac RS in Mobile phase, make dilutions with Medium to obtain a solution with a final concentration of about L/1500 mg per mL, where L is the tablet label claim, in mg.
Mobile phase—
Prepare a filtered and degassed mixture of acetonitrile, water, and concentrated phosphoric acid (500:500:0.25). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 274-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1.5 mL per minute. The column is maintained at 25
. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 274-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1.5 mL per minute. The column is maintained at 25. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 10 µL) of the Standard solution and Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of etodolac dissolved at the times specified.
Tolerances—
The percentages of the labeled amount of C17H21NO3 dissolved at the times specified conform to Acceptance Table 2.
| Time (hours) | Amount dissolved |
|---|---|
| 2 | between 10% and 30% |
| 4 | between 20% and 45% |
| 8 | between 40% and 65% |
| 18 | not less than 80% |
Uniformity of dosage units 905:
meet the requirements.
905:
meet the requirements.
Chromatographic purity—
Diluent, Mobile phase, and System suitability solution—
Proceed as directed in the Assay.
Test solution—
Use the Assay preparation.
Chromatographic system—
Prepare as directed in the Assay. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.8 for etodolac related compound A and 1.0 for etodolac; the resolution, R, between etodolac related compound A and etodolac is not less than 2.5; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Inject a volume (about 10 µL) of the Test solution into the chromatograph, record the chromatogram, and measure all of the peak areas. Calculate the percentage of each impurity in the portion of Tablets taken by the formula:
100(ri / rs)
in which ri is the peak area for each impurity, and rS is the sum of the areas of all the peaks: not more than 0.2% of any individual impurity is found; and not more than 0.75% of total impurities is found.
Assay—
Diluent—
Use acetonitrile.
Mobile phase—
Prepare a filtered and degassed mixture of acetonitrile, water, and phosphoric acid (500:500:0.25). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
System suitability solution—
Dissolve accurately weighed quantities of USP Etodolac RS and USP Etodolac Related Compound A RS in Diluent, and quantitatively dilute with Diluent to obtain a solution having known concentrations of about 0.48 mg per mL and 0.05 mg per mL, respectively.
Standard preparation—
Dissolve an accurately weighed quantity of USP Etodolac RS in Diluent, and quantitatively dilute with Diluent to obtain a solution having a known concentration of about 0.6 mg per mL.
Assay preparation—
[note—Do not finely powder Tablets. ] Weigh and powder not fewer than 20 Tablets, and transfer an accurately weighed portion of the powder, equivalent to about 600 mg of etodolac, to a 200-mL volumetric flask. Add about 100 mL of Diluent, mix, and shake for 40 minutes by mechanical means. Dilute with Diluent to volume, and mix. Pass through a filter having a 0.45-µm porosity, discarding the first 3 mL of the filtrate. Transfer 2.0 mL of the filtrate to a 10-mL volumetric flask, dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 274-nm detector, a 4.0-mm × 4.0-cm guard column that contains 5-µm packing L1, and a 4.0-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.8 for etodolac related compound A and 1.0 for etodolac; the resolution, R, between etodolac related compound A and etodolac is not less than 2.5; and the tailing factor is not more than 2.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 274-nm detector, a 4.0-mm × 4.0-cm guard column that contains 5-µm packing L1, and a 4.0-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.8 for etodolac related compound A and 1.0 for etodolac; the resolution, R, between etodolac related compound A and etodolac is not less than 2.5; and the tailing factor is not more than 2.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of etodolac (C17H21NO3) in the portion of Tablets taken by the formula:
1000C(rU / rS)
in which C is the concentration, in mg per mL, of USP Etodolac RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Clydewyn M. Anthony, Ph.D.
Senior Scientific Liaison 1-301-816-8139 |
(SM22010) Monographs - Small Molecules 2 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
|
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
USP35–NF30 Page 3142
Pharmacopeial Forum: Volume No. 31(4) Page 1068