Indomethacin Suppositories

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

2 IDENTIFICATION

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

B. The UV spectrum 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: Prepare 0.1% of formic acid by diluting 1 mL of formic acid with water to 1 L.

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

Diluent: Mobile phase adjusted with 0.2 M sodium hydroxide (NaOH) to a pH of 8.0

System suitability solution: 0.002 mg/mL of USP Indomethacin RS, 0.002 mg/mL of USP Indomethacin Related Compound A RS, and 0.01

mg/mL of USP Indomethacin Related Compound B RS in Diluent

Standard solution: 0.5 mg/mL of USP Indomethacin RS in Diluent. Sonicate if necessary.

Sample solution: Prepare a solution nominally equivalent to 0.5 mg/mL of indomethacin in Diluent as follows. Mash NLT 10 Suppositories in a beaker, and heat (at about 50°) on a water bath until melted. Mix well and cool. Transfer a portion of the mass equivalent to 10 mg of indomethacin into a 20-mL volumetric flask and add 10 mL of acetonitrile. Heat in a water bath at 50° to dissolve, and dilute with Diluent to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: PDA (scan 200-600 nm). Calculations should be based on the chromatograms collected at 240 nm. For Identification test B, use spectra at the scanned range.

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

Column temperature: 30°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 4 between indomethacin related compound A and indomethacin related compound B, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response 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: 0.1 M, pH 7.2 phosphate buffer (see Reagents, Indicators, and Solutions-Buffer Solutions); 900 mL

Apparatus 2: 50 rpm

Time: 60 min

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

Sample solution: Proceed as directed for sample per Dissolution (711). Dilute with Medium as needed.

Instrumental conditions

Mode: UV

Analytical wavelength: 320 nm

Analysis

Samples: Standard solution and Sample solution

Tolerances: NLT 75% (Q) of the labeled amount of indomethacin (C₁₉H₁₆ClNO₄) is dissolved.

Change to read:

4.2 UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements (CN 1-Aug-2023)

Diluent: Methanol and glacial acetic acid (199:1)

Standard solution: 25 µg/mL of USP Indomethacin RS in Diluent

Sample solution: Place 1 Suppository into a 100-mL volumetric flask containing 80 mL of Diluent, shake by mechanical means until the Suppository is dissolved, and dilute with Diluent to volume. Filter a portion of the solution, discarding the first 15 mL of the filtrate, and dilute a volume of the clear filtrate with the Diluent to obtain a solution having a concentration of 25 µg/mL of indomethacin.

Instrumental conditions

Mode: UV

Detector: 320 nm

Blank: Diluent

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of indomethacin (C₁₉H₁₆ClNO₄) in the Suppository taken:

Result = (A_U/A_S) × (C_S/C_U) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

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

(CN 1-Aug-2023)

5 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Indomethacin RS

USP Indomethacin Related Compound A RS

5-Methoxy-2-methyl-3-indoleacetic acid.

C₁₂H₁₃NO₃  219.24

USP Indomethacin Related Compound B. RS

4-Chlorobenzoic acid.

C₇H₅ClO₂  156.57