Indomethacin Oral Suspension
» Indomethacin Oral Suspension contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of indomethacin (C19H16ClNO4).
Packaging and storage—
Preserve in tight, light-resistant containers.
USP Reference standards 
11
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11—
USP Indomethacin RS 
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Identification—
A:
Mix a portion of Oral Suspension, equivalent to about 25 mg of indomethacin, with 25 mL of a 1 in 200 solution of glacial acetic acid in methanol, and filter. Separately apply 2 µL of the filtrate so obtained (test solution) and 2 µL of a Standard solution in methanol containing 1 mg of USP Indomethacin RS per mL to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture, and dry the spots with the aid of a current of air. Develop the chromatogram in a solvent system consisting of a mixture of chloroform and glacial acetic acid (19:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, allow it to dry, and locate the spots under short-wavelength UV light: the intensity and RF value of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.
621) coated with a 0.25-mm layer of chromatographic silica gel mixture, and dry the spots with the aid of a current of air. Develop the chromatogram in a solvent system consisting of a mixture of chloroform and glacial acetic acid (19:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, allow it to dry, and locate the spots under short-wavelength UV light: the intensity and RF value of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.
B:
The retention time of the indomethacin 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—
Medium:
0.01 M pH 7.2 phosphate buffer prepared by dissolving 1.36 g of monobasic potassium phosphate in 1 L of water and adjusting with 0.1 N sodium hydroxide to a pH of 7.2 ± 0.1; 900 mL.
Apparatus 2:
50 rpm.
Time:
20 minutes.
Procedure—
Transfer to the surface of the Medium in the dissolution vessel an accurately measured volume of Oral Suspension, freshly mixed and free from air bubbles, equivalent to about 25 mg of indomethacin. Determine the amount of C19H16ClNO4 dissolved from UV absorbances at the wavelength of maximum absorbance at about 320 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 Indomethacin RS in the same Medium. [note—An amount of methanol not to exceed 1.0% of the volume of the Standard solution may be used to bring the USP Reference Standard into solution prior to dilution with Medium, and the solution may be sonicated to effect complete dissolution of the USP Reference Standard. ]
Tolerances—
Not less than 80% (Q) of the labeled amount of C19H16ClNO4 is dissolved in 20 minutes.
Uniformity of dosage units 905—
905—
for oral suspension packaged in single-unit containers:
meets the requirements.
Deliverable volume 698—
698—
for oral suspension packaged in multiple-unit containers:
meets the requirements.
pH 791:
between 2.5 and 5.0.
791:
between 2.5 and 5.0.
Limit of 4-chlorobenzoic acid—
Using the chromatograms obtained as directed for the Assay, calculate the percentage of 4-chlorobenzoic acid (C7H5ClO2) in the Oral Suspension taken by the formula:
5(C4 / CA)(rA / r4)
in which C4 is the concentration, in µg per mL, of 4-chlorobenzoic acid in the Standard 4-chlorobenzoic acid preparation; CA is the quantity, in mg, of indomethacin (C19H16ClNO4) in the portion of Oral Suspension taken to prepare the Assay preparation, determined as directed in the Assay; and rA and r4 are the 4-chlorobenzoic acid peak responses obtained from the Assay preparation and the Standard 4-chlorobenzoic acid preparation, respectively: not more than 0.44% is found.
Content of sorbic acid (if present)—
Using the chromatograms obtained as directed for the Assay, calculate the quantity, in mg, of sorbic acid (C6H8O2) in each mL of the Oral Suspension taken by the formula:
50(C/V)(rU / rS)
in which C is the concentration, in mg per mL, of sorbic acid in the Standard indomethacin preparation; V is the volume, in mL, of Oral Suspension taken to prepare the Assay preparation; and rU and rS are the sorbic acid peak responses obtained from the Assay preparation and the Standard indomethacin preparation, respectively. It contains between 80% and 120% of the labeled amount.
Assay—
Phosphoric acid solution—
Dilute 2 mL of phosphoric acid with water to make 1000 mL of solution.
Solvent mixture—
Prepare a solution consisting of a mixture of dehydrated alcohol and butyl alcohol (8:5).
Mobile phase—
Prepare a suitable mixture of Phosphoric acid solution and Solvent mixture (610:390), pass through a suitable filter having a 0.5-µm or finer porosity, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard indomethacin preparation—
Transfer about 40 mg of USP Indomethacin RS, accurately weighed, to a 50-mL volumetric flask. Where the Oral Suspension is represented as containing a stated amount of sorbic acid, add 40J mg of sorbic acid, accurately weighed, J being the ratio of the labeled amount, in mg, of sorbic acid to the labeled amount, in mg, of indomethacin per mL of the Oral Suspension. Add 10 mL of Phosphoric acid solution and 15 mL of Solvent mixture, and sonicate for 5 minutes. Dilute with Phosphoric acid solution to volume, and mix. This solution contains about 0.8 mg of USP Indomethacin RS and, where added, about 0.8J mg of sorbic acid.
Standard 4-chlorobenzoic acid preparation—
[note—Prepare this Standard 4-chlorobenzoic acid preparation and chromatograph it as directed under Chromatographic system and Procedure only if the test for Limit of 4-Chlorobenzoic acid is being performed. ] Dissolve a suitable quantity of 4-chlorobenzoic acid, accurately weighed, in Solvent mixture to obtain a solution having a known concentration of about 0.09 mg per mL. Transfer 1.0 mL of this solution to a 50-mL volumetric flask containing 15 mL of Solvent mixture, dilute with Phosphoric acid solution to volume, and mix. This solution contains about 1.8 µg of 4-chlorobenzoic acid per mL.
Assay preparation—
Transfer an accurately measured volume of Oral Suspension, freshly mixed and free from air bubbles, equivalent to about 40 mg of indomethacin, to a 50-mL volumetric flask, add 15 mL of Solvent mixture, and sonicate for 10 minutes. Dilute with Phosphoric acid solution to volume, mix, and pass through a suitable filter having a 0.5-µm or finer porosity.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 240-nm detector and an 8-mm × 10-cm column that contains packing L1. The flow rate is about 3 mL per minute. Chromatograph the Standard indomethacin preparation, and record the peak responses as directed for Procedure: the capacity factor, k¢, for indomethacin is not less than 2.5; the column efficiency determined from the analyte peak is not less than 500 theoretical plates; the resolution, R, between sorbic acid (where present) and indomethacin is not less than 4.0; the tailing factor for the analyte peak(s) is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%. Chromatograph the Standard 4-chlorobenzoic acid preparation, and record the peak responses as directed for Procedure: the capacity factor, k¢, for the 4-chlorobenzoic acid peak, is not less than 1.0; and the relative standard deviation for replicate injections is not more than 2.5%.
621)—
The liquid chromatograph is equipped with a 240-nm detector and an 8-mm × 10-cm column that contains packing L1. The flow rate is about 3 mL per minute. Chromatograph the Standard indomethacin preparation, and record the peak responses as directed for Procedure: the capacity factor, k¢, for indomethacin is not less than 2.5; the column efficiency determined from the analyte peak is not less than 500 theoretical plates; the resolution, R, between sorbic acid (where present) and indomethacin is not less than 4.0; the tailing factor for the analyte peak(s) is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%. Chromatograph the Standard 4-chlorobenzoic acid preparation, and record the peak responses as directed for Procedure: the capacity factor, k¢, for the 4-chlorobenzoic acid peak, is not less than 1.0; and the relative standard deviation for replicate injections is not more than 2.5%.
Procedure—
Separately inject equal volumes (about 15 µL) of the Standard indomethacin preparation, the Standard 4-chlorobenzoic acid 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 indomethacin (C19H16ClNO4) in each mL of the Oral Suspension taken by the formula:
50(C/V)(rU / rS)
in which C is the concentration, in mg per mL, of USP Indomethacin RS in the Standard indomethacin preparation; V is the volume, in mL, of Oral Suspension taken; and rU and rS are the peak responses of the analyte obtained from the Assay preparation and the Standard indomethacin 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 3500
Pharmacopeial Forum: Volume No. 30(1) Page 110