Ketoprofen Extended-Release 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

Ketoprofen Extended-Release Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of ketoprofen (C₁₆H₁₄O₃ ).

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.

Change to read:

B. Spectroscopic Identification Tests 〈197〉Ultraviolet-Visible Spectroscopy: 197U. (CN 1-May-2020) The UV spectrum from the Sample solution in the Analysis for the Dissolution section corresponds to the spectrum from the Standard solution.

3 ASSAY

Procedure

[Note—Protect the Standard solution and Sample solution from light.]

Mobile phase: Acetonitrile, water, and glacial acetic acid (90:110:1)

Standard stock solution: 0.24 mg/mL of USP Ketoprofen RS in Mobile phase

Standard solution: 0.024 mg/mL of USP Ketoprofen RS in Mobile phase, from the Standard stock solution

System suitability solution: 0.25 mg/mL of USP Ketoprofen RS and 0.5 mg/mL of USP Ketoprofen Related Compound A RS in Mobile phase.

Pipet 4.0 mL of this solution into a 50-mL volumetric flask, and dilute with Mobile phase to volume.

Sample solution: Remove completely the contents of NLT 20 Capsules, and transfer a quantity of the beads, equal to 200 mg of ketoprofen, to a 250-mL volumetric flask. Add 150 mL of Mobile phase and mix; bring to volume. Centrifuge, and pipet 3.0 mL of clear supernatant that contains about 2.4 mg of ketoprofen into a 100-mL volumetric flask. Dilute with Mobile phase to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

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

Flow rate: 1.2 mL/min

Injection size: 20 μL

System suitability

Samples: Standard solution and System suitability solution

Suitability requirements

Resolution: NLT 3.0 between ketoprofen and ketoprofen related compound A, System suitability solution

Tailing factor: NMT 1.5 for the ketoprofen peak, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₆H₁₄O₃ in the portion of Capsules taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r = peak response from the Sample solution

r = peak response from the Standard solution

C = concentration of USP Ketoprofen RS in the Standard solution (mg/mL)

C = concentration of ketoprofen in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: pH 6.8 phosphate buffer; 1000 mL

Apparatus 2: 50 rpm

Time: 1, 4, and 8 h

Detector: UV 258 nm

Standard solution: About 0.1 mg/mL of USP Ketoprofen RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter of 10-μm pore size, then pass the filtrate through a suitable filter of 0.45-μm pore size.

Capsules labeled to contain 200 mg: In a test tube, dilute 5.0 mL of filtrate with 5.0 mL of Medium.

Capsules labeled to contain 150 mg: In a test tube, dilute 6.0 mL of filtrate with 3.0 mL of Medium.

Capsules labeled to contain 100 mg: No dilution is necessary.

Capsule blank: Place 10 empty, clean Capsules of the appropriate dosage into a 1000-mL volumetric flask. Add about 800 mL of Medium at 37°. Stir until Capsule shells are disintegrated. After equilibration to room temperature, dilute with Medium to volume. Transfer 100.0 mL to a 1000-mL volumetric flask, and dilute with Medium to volume. Pass through a suitable filter of 10-μm pore size, then pass the filtrate through a suitable filter of 0.45-μm pore size.

Capsules labeled to contain 200 mg: In a flask, dilute 25.0 mL with 25.0 mL of Medium.

Capsules labeled to contain 150 mg: In a flask, dilute 30.0 mL with 15.0 mL of Medium.

Capsules labeled to contain 100 mg: No dilution is necessary.

Analysis

Samples: Standard solution, Sample solution, and Capsule blank, using Medium as the blank

Calculate the concentration, in mg/mL, of ketoprofen in the sample withdrawn at each time point:

Result = (A_U − A_CB) × (C_S/A_S)

A_U = absorbance of the Sample solution

A_CB = absorbance of the Capsule blank

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

A _S= absorbance of the Standard solution

Calculate the percentage of ketoprofen dissolved at each time point:

Result = (D + ΣR) × 100/L

D = [amount dissolved (mg)] = volume (mL) remaining before draw × concentration (mg/mL) of sample withdrawn at the

sampling time point

R = [amount removed (mg)] = volume (mL) of sample withdrawn × concentration (mg/mL) of sample withdrawn at each time point

10₀ = conversion factor for percentage

L = Capsule label claim (mg)

Tolerances: The percentage of the labeled amount of ketoprofen released at the times specified conforms to Acceptance Table 2.

Table 2

Uniformity of Dosage Units 〈905〉: Meet the requirements

Procedure for content uniformity:

[Note—Protect the Standard solution and Sample solution from light.]

Mobile phase, Standard solution, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Sample solution: Transfer the contents of 10 Capsules, 1 Capsule each, to each of 10 250-mL volumetric flasks, add about 150 mL of Mobile phase to each flask, and stir for 2 h. Dilute with Mobile phase to volume, and mix. Centrifuge, and pipet a volume of clear supernatant that contains about 2.4 mg of ketoprofen into a 100-mL volumetric flask. Dilute with Mobile phase to volume.

System suitability

Samples: Standard solution and System suitability solution

Suitability requirements

Resolution: NLT 3.0 between ketoprofen and ketoprofen related compound A, System suitability solution

Tailing factor: NMT 1.5 for the ketoprofen peak, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₆H₁₄O₃ in each Capsule:

Result = (r_U/r_S)x(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 Ketoprofen RS in the Standard solution (mg/mL)

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

5 SPECIFIC TESTS

Water Determination, Method I〈921〉: NMT 3.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Ketoprofen RS

USP Ketoprofen Related Compound A RS

α-Methyl-3-(4-methylbenzoyl) benzeneacetic acid.