Indomethacin Capsules

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 Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of indomethacin (C₁₉H₁₆ClNO₄).

2 IDENTIFICATION

A.

Standard: A solution of 25 mg of USP Indomethacin RS in 5 mL of acetone recrystallized and prepared similarly as for the Sample.

Sample: Shake a portion of the contents of Capsules, nominally equivalent to about 50 mg of indomethacin, with 10 mL of acetone for about 2 min, and filter. Transfer 5 mL of the filtrate to a stoppered flask, add 20 mL of water, and shake for about 2 min until a precipitate forms and crystallizes. Filter, and collect the crystals. Dry the crystals in air, then dry at a pressure below 5 mm of mercury at 100° for 2 h.

Acceptance criteria: The IR absorption spectrum of a potassium bromide dispersion of the Sample exhibits maxima only at the same wavelengths as those of the Standard.

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: Phosphoric acid and water (2:1000)

Mobile phase: Acetonitrile and Solution A (45:55)

Diluent: Mobile phase adjusted with 0.2 N sodium hydroxide to a pH of 6.0

Standard stock solution: 1 mg/mL of USP Indomethacin RS prepared as follows. Transfer a suitable quantity of USP Indomethacin RS to an adequate volumetric flask, add 50% of the final volume of acetonitrile, and dilute with Diluent to final volume.

Standard solution: 0.04 mg/mL of USP Indomethacin RS in Diluent from Standard stock solution

Sample stock solution: Nominally 1 mg/mL of indomethacin prepared as follows. Transfer a suitable portion of the contents from NLT 20 Capsules to an adequate volumetric flask, add 50% of the final volume of acetonitrile, and sonicate for about 10 min with intermittent shaking. Add about 25% of the final volume of Diluent and sonicate for about 10 min with intermittent shaking. Dilute with Diluent to final volume and mix. Allow the resulting mixture to stand until a clear supernatant is obtained. Use the clear supernatant.

Sample solution: Nominally 0.04 mg/mL of indomethacin in Diluent from Sample stock solution. Pass through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability..)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1.5 mL/min

Injection volume: 25 µL

Run time: NLT 2 times the retention time of indomethacin

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of indomethacin (C₁₉H₁₆ClNO₄) in the portion of Capsules 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 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Medium: pH 7.2 phosphate buffer (see Reagents, Indicators, and Solutions-Buffer Solutions) and water (1:4); 750 mL

Apparatus 1: 100 rpm

Time: 20 min

Standard solution: USP Indomethacin RS at a known concentration in Medium

Sample solution: Filter a portion of the solution under test and suitably dilute with Medium, if necessary.

Instrumental conditions

Mode: UV

Analytical wavelength: Maximum absorbance at about 318 nm

Analysis

Samples: Standard solution and Sample solution

Tolerances: NLT 80% (Q) of the labeled amount of indomethacin (C1,HCINO) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

5.1 ORGANIC IMPURITIES

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

System suitability stock solution: 0.2 mg/mL each of USP Indomethacin Related Compound A RS and USP Indomethacin Related Compound B RS prepared as follows. Transfer suitable quantities of USP Indomethacin Related Compound A RS and USP Indomethacin Related Compound B RS to an adequate volumetric flask, add 40% of the final volume of acetonitrile, and sonicate to dissolve. Dilute with Diluent to final volume.

System suitability solution: 0.002 mg/mL each of USP Indomethacin Related Compound A RS and USP Indomethacin Related Compound B RS, and 0.4 mg/mL of USP Indomethacin RS in Diluent from System suitability stock solution and Standard stock solution

Sensitivity solution: 0.2 µg/mL of USP Indomethacin RS in Diluent from Standard stock solution

Standard solution: 0.002 mg/mL of USP Indomethacin RS in Diluent from Standard stock solution

Sample solution: Nominally 0.4 mg/mL of indomethacin in Diluent from Sample stock solution

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

Suitability requirements

Resolution: NLT 1.5 between indomethacin related compound A and indomethacin related compound B, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of indomethacin related compound A, indomethacin related compound B, and any unspecified degradation

product in the portion of Capsules taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak response of indomethacin related compound A, or indomethacin related compound B, or any unspecified degradation product 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)

F = relative response factor of each individual impurity (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

Table 1

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.

USP REFERENCE STANDARDS (11)

USP Indomethacin RS

USP Indomethacin Related Compound A RS

2-(5-Methoxy-2-methyl-1H-indol-3-yl)acetic acid.

C₁₂H₁₃NO₃  219.24

USP Indomethacin Related Compound B RS

4-Chlorobenzoic acid.

C₇H₅ClO₂  156.57