Fenofibrate Tablets

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

Fenofibrate Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of fenofibrate (C₂₀H₂₁CIO₄).

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.

Add the following:

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay (USP 1-May-2019)

2 ASSAY

Change to read:

2.1 PROCEDURE

Acidified water: Adjust the pH of water with phosphoric acid to 2.5 ± 0.1.

Mobile phase: Acetonitrile and Acidified water (70:30)

System suitability stock solution: 0.1 mg/mL each of USP Fenofibrate Related Compound A RS and USP Fenofibrate Related Compound B RS in acetonitrile

System suitability solution: 0.5 µg/mL each of USP Fenofibrate Related Compound A RS and USP Fenofibrate Related Compound B RS in Mobile phase from the System suitability stock solution

Standard solution: 0.05 mg/mL of USP Fenofibrate RS in Mobile phase

Sample stock solution: Prepare a solution containing a nominal concentration of approximately 2-4 mg/mL of fenofibrate by disintegrating a suitable number of Tablets with sonication in Acidified water, using 30% of the final volume of the flask. Add acetonitrile to approximately 90% of flask volume, and sonicate with periodic swirling. Dilute with acetonitrile to volume.

Sample solution: Nominally 0.05 mg/mL of fenofibrate in Mobile phase, from the Sample stock solution. Filter a portion of this solution, discarding the first few milliliters of the filtrate.

2.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 286 nm. For Identification B, use a diode array detector in the range of 200-400 nm. (USP 1-May-2019)

Column: 4.0-mm x 25-cm or 4.6-mm × 25-cm; 5-µm or 4-um packing L1

Column temperature: 35°

Flow rate: 1.2 mL/min

Injection volume: 10 µL

Run time: NLT 2 times the retention time of the fenofibrate peak (USP 1-May-2019)

2.3 System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between fenofibrate related compound A and fenofibrate related compound B peaks, System suitability solution

Relative standard deviation: NMT 2.0% for the fenofibrate peak, Standard solution

2.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fenofibrate (C₂₀H₂₁CIO₄) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of fenofibrate from the Sample solution

r_S = peak response of fenofibrate from the Standard solution

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

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

Acceptance criteria: 90.0%-110.0%

3 PERFORMANCE TESTS

3.1 DISSOLUTION (711)

3.1.1 Test 1

Medium: 0.025 M sodium dodecyl sulfate in water: 1000 mL

Apparatus 2: 50 rpm

Time: 30 min

Acidified water: Adjust the pH of water with phosphoric acid to 2.5 ± 0.1.

Mobile phase: Acetonitrile and Acidified water (70:30)

Standard stock solution: 2.5 mg/mL of USP Fenofibrate RS in acetonitrile

Standard solution: Dilute the Standard stock solution with Medium to obtain a final concentration of about (0.001 x L) mg/mL, where L is the label claim, in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first few milliliters of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 286 nm

Column: 2-mm x 3-cm; 3-µm packing L1

Column temperature: 35°

Flow rate: 1.2 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NLT 0.9 and NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fenofibrate (C₂₀H₂₁CIO₄) dissolved:

Result = (r_U/r_S) x C_S x V x (1/L) x 100 

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of Medium , 1000 mL

L = label claim (mg /Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of fenofibrate (C₂₀H₂₁CIO₄) is dissolved.

3.1.2 Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2

Medium: 0.05 M sodium dodecyl sulfate in water; 1000 mL

Apparatus 2: 50 rpm

Time: 30 min

Buffer: 136 mg/L of monobasic potassium phosphate in water. Adjust with diluted phosphoric acid to a pH of 2.9 ± 0.05.

Mobile phase: Methanol and Buffer (80:20)

Standard solution: (0.001 x L) mg/mL of USP Fenofibrate RS in Mobile phase, where L is the label claim, in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first few milliliters of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 286 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Flow rate: 1.0 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fenofibrate (C₂₀H₂₁CIO₄) dissolved:

Result = (r_U/r_S) x C_S x V x (1/L) x 100 

r_U = peak response of fenofibrate from the Sample solution

r_S = peak response of fenofibrate from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of Medium, 1000 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of fenofibrate (C₂₀H₂₁CIO₄) is dissolved.

3.1.3 Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3

For Tablet strengths other than 40 and 120 mg of fenofibrate

Medium: 0.05 M sodium lauryl sulfate in water; 1000 mL

Apparatus 2: 50 rpm

Time: 45 min

Standard solution: 0.012 mg/mL of USP Fenofibrate RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first few milliliters of the filtrate and appropriately diluting with Medium to a concentration similar to that of the Standard solution.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857)..)

Mode: UV

Analytical wavelength: 292 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fenofibrate (C₂₀H₂₁CIO₄) dissolved:

Result = (A_U/A_S) x C_S x V x D x (1/L) x 100 

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of Medium, 1000 mL

D = dilution factor for the Sample solution

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of fenofibrate (C₂₀H₂₁CIO₄) is dissolved.

For Tablets labeled to contain 40 and 120 mg of fenofibrate

Medium: 0.75% sodium lauryl sulfate in water: 900 mL

Apparatus 2: 75 rpm

Time: 45 min

Buffer: 2.72 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 2.9 ± 0.05.

Mobile phase: Methanol and Buffer (85:15)

Standard stock solution: 2.22 mg/mL of USP Fenofibrate RS prepared as follows. Transfer a suitable amount of USP Fenofibrate RS into a suitable volumetric flask. Add 50% of the flask volume of acetonitrile, sonicate to dissolve, and dilute with Medium to volume.

Standard solution: (L/900) mg/mL of USP Fenofibrate RS in Medium from Standard stock solution, where L is the label claim, in mg/Tablet Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first few milliliters of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 285 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 2 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of fenofibrate

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fenofibrate (C₂₀H₂₁CIO₄) dissolved:

Result = (r_U/r_S) x C_S x V x (1/L) x 100 

r_U = peak response of fenofibrate from the Sample solution

r_S = peak response of fenofibrate from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of fenofibrate (C₂₀H₂₁CIO₄) is dissolved.

3.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

4 IMPURITIES

Change to read:

ORGANIC IMPURITIES

Acidified water, Mobile phase, System suitability solution, Sample stock solution, and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 0.25 µg/mL of USP Fenofibrate RS in Mobile phase (USP 1-May-2019)

Standard solution: 0.5 µg/mL of USP Fenofibrate RS in Mobile phase

Sample solution: Nominally 0.5 mg/mL of fenofibrate in Mobile phase, from the Sample stock solution. Filter a portion of this solution, discarding the first few milliliters of filtrate.

System suitability

Samples: System suitability solution, Sensitivity solution, (USP 1-May-2019) and Standard solution

Suitability requirements

Resolution: NLT 2.0 between fenofibrate related compound A and fenofibrate related compound B, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-May-2019)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each degradation product (USP 1-May-2019) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) x 100

r_U = peak response of each degradation product (USP 1-May-2019) from the Sample solution

r_S = peak response of fenofibrate from the Standard solution

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

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

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a Disregard this impurity. It is a process impurity and is controlled in the drug substance monograph.

^b 1-Methylethyl 2-[[2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoyl)oxy]-2-methylpropanoate.

5 ADDITIONAL REQUIREMENTS

5.1 PACKAGING AND STORAGE

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

5.2 LABELING

When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

5.3 USP REFERENCE STANDARDS (11)

USP Fenofibrate RS

USP Fenofibrate Related Compound A RS

(4-Chlorophenyl) (4-hydroxyphenyl)methanone.

C₁₃H₉CIO₂ 232.66

USP Fenofibrate Related Compound B RS

2-[4-(4-Chlorobenzoyl)phenoxy)-2-methylpropanoic acid, or fenofibric acid.

C₁₇H₁₅CIO₄ 318.75