Fenofibrate Capsules
DEFINITION
Fenofibrate Capsules contains NLT 90.0% and NMT 110.0% of the labeled amount of fenofibrate (C20H21ClO4).
IDENTIFICATION
• The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
[NoteUse Sample stock solution 2 for Capsules labeled to meet the requirements of Dissolution Test 2. For all other products, use Sample stock solution 1. ]
Solution A:
136 mg/L of monobasic potassium phosphate in water. Adjust with dilute phosphoric acid (1 in 10) to a pH of 2.9 ± 0.05.
Mobile phase:
Methanol and Solution A (4:1)
Standard solution:
67 µg/mL of USP Fenofibrate RS in Mobile phase
Sample stock solution 1:
Accurately weigh the contents of NLT 20 Capsules. Mix the contents, and transfer a weighed portion of the powder, equivalent to about 67 mg of fenofibrate, to a 100-mL volumetric flask. Add 80 mL of Mobile phase, sonicate for 10 min, stir for 15 min, and dilute with Mobile phase to volume.
Sample stock solution 2 (For Capsules labeled to meet the requirements of Dissolution Test 2):
Weigh the contents of NLT 20 Capsules. Mix the contents, melt in an oven at 80 for NLT 30 min, and homogenize. Allow the sample to solidify. Transfer a weighed portion of the sample, equivalent to about 67 mg of fenofibrate, to a 100-mL volumetric flask, dissolve in 30 mL of methanol with the aid of a mechanical shaker for NLT 4 h, and dilute with Mobile phase to volume.
Sample solution:
67 µg/mL of fenofibrate from the designated Sample stock solution, in Mobile phase. Pass a portion of this solution through a PVDF filter of 0.45-µm pore size, discarding the first 5 mL.
Chromatographic system
Mode:
LC
Detector:
UV 285 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 6000 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C20H21ClO4 in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
90.0%110.0%
PERFORMANCE TESTS
• Dissolution 711
Test 1
Medium:
0.05 M sodium lauryl sulfate in water; 1000 mL, deaerated
Apparatus 2:
75 rpm
Time:
40 min
Solution A and Mobile phase:
Proceed as directed in the Assay.
Standard solution:
(0.001 × L) mg/mL of USP Fenofibrate RS in Mobile phase, where L is the Capsule label claim, in mg
Sample solution:
Pass a portion of the solution under test through a suitable polyvinylidene difluoride (PVDF) filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 285 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1 mL/min
Injection size:
10 µL for Capsules labeled to contain 67 mg; 5 µL for Capsules labeled to contain 134 or 200 mg
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 4000 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C20H21ClO4 dissolved:
Result = (rU/rS) × CS × V × (100/L)
Tolerances:
NLT 70% (Q) of the labeled amount of C20H21ClO4 is dissolved.
Test 2:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:
Phosphate buffer pH 6.8 ± 0.1 containing 0.1% pancreatin and 2% polysorbate 80; 900 mL, deaerated by vacuum
Apparatus 2:
75 rpm with sinkers (see Dissolution 711, Figure 2a)
Time:
2 h
Detector:
UV 288 nm
Standard solution:
(L/1000) mg/mL of USP Fenofibrate RS in Medium, where L is the Capsule label claim, in mg. A volume of methanol, not exceeding 10%, can be used in the first dilution to solubilize fenofibrate.
Sample solution:
Pass 20 mL of the solution under test through a suitable PVDF filter of 0.45-µm pore size, discarding the first 2 mL.
Path length:
0.1 cm, flow cell
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C20H21ClO4 dissolved:
Result = (AU/AS) × CS × V × (100/L)
Tolerances:
NLT 80% (Q) of the labeled amount of C20H21ClO4 is dissolved.
Test 3:
If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 3.
Medium:
0.72% sodium lauryl sulfate in water; 1000 mL, deaerated
Apparatus 2:
75 rpm, with sinkers with three prongs
Time:
30 min
Standard solution:
L/10 mg/mL of USP Fenofibrate RS in methanol, where L is the Capsule label claim in mg. Transfer 10.0 mL of this solution to a 1000-mL volumetric flask, and dilute with Medium to volume.
Sample solution:
Pass a portion of the solution under test through a suitable PVDF filter of 0.45-µm pore size. Dilute with Medium, if necessary.
Detection:
UV 290 nm
Blank:
Medium
Calculate the percentage of fenofibrate dissolved:
Result = (AU/AS) × (CS/L) × D × V × 100
Tolerances:
NLT 80% (Q) of the labeled amount of fenofibrate is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
Procedure for content uniformity
Solution A, Mobile phase, Standard solution, Chromatographic system, System suitability, and Analysis:
Proceed as directed in the Assay, except to prepare the Sample stock solution and Sample solution as follows.
Sample stock solution:
Place 1 Capsule in a suitable volumetric flask, add Solution A to 10%20% of the final volume, and stir for 20 min to disintegrate the Capsule. Fill the flask to about 80% with methanol, sonicate for 10 min, stir for 15 min, and dilute with methanol to volume to obtain a solution having a known concentration of about 0.40.7 mg/mL of fenofibrate, based on the label claim.
Sample solution:
6070 µg/mL of fenofibrate, from the Sample stock solution, in Mobile phase. Pass a portion of this solution through a PVDF filter of 0.45-µm pore size, discarding the first 5 mL.
IMPURITIES
Organic Impurities
[NoteUse Sample solution 2 for Capsules labeled to meet the requirements of Dissolution Test 2. For all other products, use Sample solution 1. ]
• Procedure
Solution A:
136 mg/L of monobasic potassium phosphate. Adjust with dilute phosphoric acid (1 in 10) to a pH of 2.9 ± 0.05.
Mobile phase:
Methanol and Solution A (4:1)
Standard solution:
3.35 µg/mL of USP Fenofibrate RS and 3.35 µg/mL of USP Fenofibrate Related Compound B RS in Mobile phase
System suitability solution:
0.67 mg/mL of USP Fenofibrate RS and 3.35 µg/mL of USP Fenofibrate Related Compound B RS in Mobile phase
Quantitative limit solution:
0.67 µg/mL of USP Fenofibrate RS and 0.67 µg/mL of USP Fenofibrate Related Compound B RS in Mobile phase, from the Standard solution
Sample solution 1:
Accurately weigh the contents of NLT 20 Capsules. Mix the contents, and transfer a weighed portion of the powder, equivalent to about 67 mg of fenofibrate, to a 100-mL volumetric flask. Add 80 mL of Mobile phase, sonicate for 10 min, stir for 15 min, and dilute with Mobile phase to volume. Pass a portion of this solution through a PVDF filter of 0.45-µm pore size, discarding the first 5 mL. The final concentration based on the label claim is about 0.67 mg/mL.
Sample solution 2 (For Capsules labeled to meet the requirements of Dissolution Test 2):
Weigh the contents of NLT 20 Capsules. Mix the contents, melt in an oven at 80 for NLT 30 min, and homogenize. Allow the sample to solidify. Transfer a weighed portion of the sample, equivalent to about 67 mg of fenofibrate, to a 100-mL volumetric flask, dissolve in 30 mL of methanol with the aid of a mechanical shaker for NLT 4 h, and dilute with Mobile phase to volume. Pass through a PVDF filter of 0.45-µm pore size, discarding the first 12 mL. The final concentration based on the label claim is about 0.67 mg/mL.
Chromatographic system
Mode:
LC
Detector:
UV 285 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1 mL/min
Injection size:
20 µL
System suitability
Samples:
Standard solution, System suitability solution, and Quantitative limit solution
Suitability requirements
Resolution:
NLT 3.0 between fenofibrate and fenofibrate related compound B, System suitability solution
Column efficiency:
NLT 3000 theoretical plates for fenofibrate related compound B, System suitability solution
Tailing factor:
NMT 2.0 for fenofibrate related compound B, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Signal-to-noise ratio:
NLT 10 for the fenofibrate peak, Quantitative limit solution
Analysis
Samples:
Standard solution and designated Sample solution
Calculate the percentage of fenofibrate related compound B in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
Calculate the percentage of any other impurity in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria
Individual impurities:
NMT 0.5% for fenofibrate related compound B; NMT 0.2% for any other individual impurity
Total impurities:
NMT 2.0%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers, and store at controlled room temperature.
• Labeling:
When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 3161
Pharmacopeial Forum: Volume No. 34(2) Page 258
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