Ketoprofen Extended-Release Capsules
DEFINITION
Ketoprofen Extended-Release Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of ketoprofen (C16H14O3).
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. Ultraviolet Absorption 
197
:
The UV spectrum from the Sample solution in the Analysis for the Dissolution section corresponds to the spectrum from the Standard solution.
197:
The UV spectrum from the Sample solution in the Analysis for the Dissolution section corresponds to the spectrum from the Standard solution.
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
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:
NLT 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 = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Ketoprofen RS in the Standard solution (mg/mL) |
| CU | = | = concentration of ketoprofen in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
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.
. 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 = (AU 
ACB) × (CS/AS)
ACB) × (CS/AS)| AU | = | = absorbance of the Sample solution |
| ACB | = | = absorbance of the Capsule blank |
| CS | = | = concentration of USP Ketoprofen RS in the Standard solution (mg/mL) |
| AS | = | = absorbance of the Standard solution |
Caculate the percentage of ketoprofen dissolved at each time point:
Result = (D + SR) × 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.
| Time (h) |
Amount Dissolved |
|---|---|
| 1 | 10%–25% |
| 4 | 55%–80% |
| 8 | NLT 80% |
• Uniformity of Dosage Units 905:
Meet the requirements
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:
NLT 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 = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Ketoprofen RS in the Standard solution (mg/mL) |
| CU | = | = concentration of ketoprofen in the Sample solution (mg/mL) |
SPECIFIC TESTS
• Water Determination, Method I 921:
NMT 3.0%
921:
NMT 3.0%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers, and store at controlled room temperature.
• USP Reference Standards 11
11
USP Ketoprofen RS 
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USP Ketoprofen Related Compound A RS
-Methyl-3-(4-methylbenzoyl) benzeneacetic acid.
-Methyl-3-(4-methylbenzoyl) benzeneacetic acid.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Clydewyn M. Anthony, Ph.D.
Senior Scientific Liaison 1-301-816-8139 |
(SM22010) Monographs - Small Molecules 2 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3622
Pharmacopeial Forum: Volume No. 34(4) Page 951