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.
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
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 = (AU 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
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
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.
•  USP Reference Standards 11
USP Ketoprofen RS Click to View Structure
USP Ketoprofen Related Compound A RS
-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
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USP35–NF30 Page 3622
Pharmacopeial Forum: Volume No. 34(4) Page 951