Ibuprofen 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

Ibuprofen Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of ibuprofen (C₁₃H₁₈O₂).

2 IDENTIFICATION

A. The UV absorption spectra of the ibuprofen peak of the Sample solution exhibit maxima and minima at the same wavelengths as those of the Standard solution, as obtained in the Assay.

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

3 ASSAY

Procedure

Mobile phase: Dissolve 1.52 g of monobasic potassium phosphate in 560 mL of water. Adjust with phosphoric acid to a pH of 2.05 if necessary. Add 440 mL of tetrahydrofuran and mix.

Diluent: Methanol and water (1:1)

Standard solution: 0.4 mg/mL of USP Ibuprofen RS in Diluent

Sample solution: Nominally 0.4 mg/mL of ibuprofen in Diluent prepared as follows. Transfer a suitable amount of Oral Suspension to a suitable volumetric flask. Add about 60% of the final volume of Diluent. Sonicate for 45 min. Cool and dilute with Diluent to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identification A, use a diode-array detector in the range of 200–400 nm.

Column: 4.6-mm × 15-cm; 5-µm packing L7

Flow rate: 1.0 mL/min

Injection volume: 25 µL

Run time: NLT 1.9 times the retention time of ibuprofen

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 3.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ibuprofen (C₁₃H₁₈O₂) in the portion of Oral Suspension taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of ibuprofen from the Sample solution

rₛ = peak response of ibuprofen from the Standard solution

Cₛ = concentration of USP Ibuprofen RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of ibuprofen in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Medium: pH 7.2 phosphate buffer (see Reagents, Indicators, and Solutions—Buffer Solutions); 900 mL

Apparatus 2: 50 rpm

Time: 60 min

Buffer: Dilute 0.7 mL of phosphoric acid with water to obtain 1000 mL of 0.01 M phosphoric acid.

Mobile phase: Acetonitrile and Buffer (37:63)

Internal standard solution: 0.3 mg/mL of benzophenone in acetonitrile

Standard stock solution: Dissolve a quantity of USP Ibuprofen RS in Medium to obtain a solution with a known concentration of 0.011J mg/mL, J being the labeled amount of ibuprofen in the Oral Suspension, in mg/mL.

Standard solution: Internal standard solution and Standard stock solution (1:1), passed through a suitable filter of 0.5-µm or finer pore size

Sample stock solution: Filter a portion of the solution under test.

Sample solution: Internal standard solution and Sample stock solution (1:1), passed through a suitable filter of 0.5-µm or finer pore size

Density: Using a tared 50-mL volumetric flask, weigh 50 mL of Oral Suspension that has been previously well shaken to ensure homogeneity. Allow to stand until the entrapped air has risen, and invert carefully just prior to transferring it to the volumetric flask. From the observed weight of 50 mL of Oral Suspension, calculate the density of Oral Suspension in g/mL.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 15-cm; 5-µm packing L7

Flow rate: 2 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

[Note—The relative retention times for benzophenone and ibuprofen are 0.9 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 between benzophenone and ibuprofen

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Using an accurately tared syringe, draw about 10 mL of well-mixed Oral Suspension into the syringe, which is connected to tubing, and weigh. [Note—The tubing of the syringe is placed into a zone that is between the surface of the Medium and the top of the rotating blade.] Express the Oral Suspension into the Medium. Promptly reweigh the syringe and determine the weight, in g, of Oral Suspension added to the Medium.

Calculate the percentage of the labeled amount of ibuprofen (C₁₃H₁₈O₂) dissolved:

Result = (Rᵤ / Rₛ) × C × V × (▲d▲ (ERR 1-Jun-2022) / W) × ▲D▲ (ERR 1-Jun-2022) × (1 / L) × 100

Rᵤ = peak area ratio of ibuprofen to benzophenone from the Sample solution

Rₛ = peak area ratio of ibuprofen to benzophenone from the Standard solution

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

V = volume of Medium, 900 mL

▲d▲ (ERR 1-Jun-2022) = density of Oral Suspension (g/mL)

W = weight of the portion of Oral Suspension added to the Medium (g)

▲D▲ (ERR 1-Jun-2022) = dilution factor of the Sample solution, 2

L = label claim (mg/mL)

Tolerances: NLT 80% (Q) of the labeled amount of ibuprofen (C₁₃H₁₈O₂) is dissolved.

Uniformity of Dosage Units 〈905〉

For single-unit containers

Acceptance criteria: Meets the requirements

Deliverable Volume 〈698〉

For multiple-unit containers

Acceptance criteria: Meets the requirements

5 IMPURITIES

Organic Impurities

Mobile phase, Diluent, and Sample solution: Proceed as directed in the Assay.

System suitability solution: 0.4 mg/mL of USP Ibuprofen RS, 0.004 mg/mL each of USP Ibuprofen Related Compound C RS and USP Ibuprofen Related Compound J RS, and 0.0169 mg/mL of USP Benzoic Acid RS in Diluent

Sensitivity solution: 0.0002 mg/mL each of USP Ibuprofen Related Compound J RS and USP Ibuprofen Related Compound C RS in Diluent

Standard solution A: 0.0002 mg/mL of USP Ibuprofen RS in Diluent

Standard solution B: 0.004 mg/mL each of USP Ibuprofen Related Compound J RS and USP Ibuprofen Related Compound C RS in Diluent

Chromatographic system: Proceed as directed in the Assay, except for the Detector.

Detectors

For the quantitation of unspecified degradation products: UV 220 nm

For the quantitation of ibuprofen related compound C and ibuprofen related compound J: UV 254 nm

System suitability

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

Suitability requirements

For the quantitation of unspecified degradation products

Resolution: NLT 2.0 between benzoic acid and ibuprofen related compound J; NLT 2.0 between ibuprofen related compound J and ibuprofen related compound C; NLT 2.0 between ibuprofen related compound C and ibuprofen, System suitability solution

Relative standard deviation: NMT 10.0%, Standard solution A

For the quantitation of ibuprofen related compound J and ibuprofen related compound C

Resolution: NLT 2.0 between benzoic acid and ibuprofen related compound J; NLT 2.0 between ibuprofen related compound J and ibuprofen related compound C; NLT 2.0 between ibuprofen related compound C and ibuprofen, System suitability solution

Relative standard deviation: NMT 2.0% for ibuprofen related compound J and ibuprofen related compound C, Standard solution B

Signal-to-noise ratio: NLT 10 for ibuprofen related compound J and ibuprofen related compound C, Sensitivity solution

Analysis

Samples: Sample solution, Standard solution A, and Standard solution B

Calculate the percentage of ibuprofen related compound J and ibuprofen related compound C in the portion of Oral Suspension taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of ibuprofen related compound J or ibuprofen related compound C from the Sample solution

rₛ = peak response of ibuprofen related compound J or ibuprofen related compound C from Standard solution B

Cₛ = concentration of USP Ibuprofen Related Compound J RS or USP Ibuprofen Related Compound C RS in Standard solution B (mg/mL)

Cᵤ = nominal concentration of ibuprofen in the Sample solution (mg/mL)

Calculate the percentage of any unspecified degradation product in the portion of Oral Suspension taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of any individual unspecified degradation product from the Sample solution

rₛ = peak response of ibuprofen from Standard solution A

Cₛ = concentration of USP Ibuprofen RS in Standard solution A (mg/mL)

Cᵤ = nominal concentration of ibuprofen in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. Disregard any peaks less than 0.05%.

ᵃ Excipient, not included in the total degradation products.

6 SPECIFIC TESTS

pH 〈791〉: 3.6–4.6

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Benzoic Acid RS

USP Ibuprofen RS

USP Ibuprofen Related Compound C RS

4-Isobutylacetophenone.

C₁₂H₁₆O 176.25

USP Ibuprofen Related Compound J RS

2-(4-Isobutyrylphenyl)propanoic acid.

C₁₃H₁₆O₂ 220.26