Indomethacin Oral Suspension

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Indomethacin Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of indomethacin (C₁₉H₁₆ClNO₄).

2 IDENTIFICATION

A. The UV absorption spectrum of the indomethacin peak of the Sample solution exhibits maxima and minima at the same wavelengths as those of the Standard solution, as obtained in the Assay.

B. The retention time of the indomethacin peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 PROCEDURE

Solution A: 0.2% (v/v) phosphoric acid in water

Solution B: Dehydrated alcohol and butyl alcohol (80:50)

Mobile phase: Solution B and Solution A (39:61). Pass through a suitable filter of 0.5-µm or finer pore size.

Standard solution: 0.8 mg/mL of USP Indomethacin RS and 0.16 mg/mL of sorbic acid prepared as follows. Transfer appropriate amounts of USP Indomethacin RS and sorbic acid to a suitable volumetric flask. Add 20% of the total volume of Solution A and 30% of the total volume of Solution B, and sonicate for 5 min. Dilute with Solution A to the total volume.

Sample solution: Nominally 0.8 mg/mL of indomethacin prepared as follows. Transfer an appropriate volume of Oral Suspension, freshly mixed and free from air bubbles, to a suitable volumetric flask. Add 30% of Solution B, and sonicate for 10 min. Dilute with Solution A to volume, and pass through a suitable filter of 0.5-µm or finer pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm. For Identification A, use a diode array detector in the range of 200-400 nm.

Column: 8-mm x 10-cm; packing L1

Flow rate: 3 mL/min

Injection volume: 15 µL

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 4.0 between sorbic acid and indomethacin

Tailing factor: NMT 2.0 for indomethacin

Relative standard deviation: NMT 2.0% for indomethacin

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of indomethacin (C₁₉H₁₆ClNO₄) in the portion of Oral Suspension taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of indomethacin from the Sample solution

r_S = peak response of indomethacin from the Standard solution

C_S = concentration of USP Indomethacin RS in the Standard solution (mg/mL)

C_U = nominal concentration of indomethacin in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 OTHER COMPONENTS

5 PERFORMANCE TESTS

5.1 DISSOLUTION (711)

Buffer solution: 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

Medium: Buffer solution; 900 mL

Apparatus 2: 50 rpm

Time: 20 min

Standard solution: USP Indomethacin RS at a known concentration in Medium. [NOTE-A quantity 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 before dilution with Medium, and the solution may be sonicated to effect complete dissolution of the USP Reference Standard.]

Sample solution: Transfer to the surface of the Medium in the dissolution vessel a volume of Oral Suspension, freshly mixed and free from air bubbles, nominally equivalent to 25 mg of indomethacin. Filter portions of the solution under test, and suitably dilute with Medium if necessary.

Instrumental conditions

Mode: UV

Analytical wavelength: 320 nm

Analysis

Samples: Standard solution and Sample solution

Tolerances: NLT 80% (Q) of the labeled amount of indomethacin (C₁₉H₁₆ClNO₄) is dissolved.

5.2 UNIFORMITY OF DOSAGE UNITS (905)

For single-unit containers

Acceptance criteria: Meets the requirements

5.3 DELIVERABLE VOLUME (698)

For multiple-unit containers

Acceptance criteria: Meets the requirements

6 IMPURITIES

6.1 CONTENT OF INDOMETHACIN RELATED COMPOUND B

Solution A, Solution B, Mobile phase, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard stock solution: 0.09 mg/mL of USP Indomethacin Related Compound B RS in Solution B

OFFINAL Standard solution: 0.0018 mg/mL of USP Indomethacin Related Compound B RS prepared as follows. Transfer an adequate amount of Standard stock solution to a suitable volumetric flask containing 30% of the total volume of Solution B, and dilute with Solution A to the total volume.

System suitability

Sample: Standard solution

Suitability requirements

Capacity factor, k': NLT 1.0

Relative standard deviation: NMT 2.5%

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of indomethacin related compound B in the portion of Oral Suspension taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of indomethacin related compound B from the Sample solution

r_S = peak response of indomethacin related compound B from the Standard solution

C_S = concentration of USP Indomethacin Related Compound B RS in the Standard solution (mg/mL)

C_U = nominal concentration of indomethacin in the Sample solution (mg/mL)

Acceptance criteria: NMT 0.44%

7 SPECIFIC TESTS

PH (791): 2.5-5.0

8 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Store below 30° and avoid temperatures above 50°. Preserve in tight, light-resistant containers and protect from freezing.

USP REFERENCE STANDARDS (11)

USP Indomethacin RS

USP Indomethacin Related Compound B RS

4-Chlorobenzoic acid.

C₇H₅CIO₂ 156.57