Fenofibrate Capsules

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

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

2 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. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

3.1 PROCEDURE

Use 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 potassium phosphate, monobasic (RB 1-May-2021) 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: Nominally 67 µg/mL of fenofibrate from the designated Sample stock solution, in Mobile phase. Pass a portion of this solution through a polyvinylidene difluoride (PVDF) filter of 0.45-µm pore size, discarding the first 5 mL.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 285 nm. For Identification B, use a diode array detector in the range of 200-400 nm.

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

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 1.5 times the retention time of the fenofibrate peak

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fenofibrate (C₂₀H₂₁CIO₄) in the portion of Capsules 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 the Standard solution (µg/mL)

C_U = nominal concentration of the Sample solution (µg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711)

4.1.1 Test 1

Medium: 0.05 M sodium dodecyl sulfate (RB 1-May-2021) in water, 1000 mL, deaerated

Apparatus 2: 75 rpm

Time: 40 min

Solution A and Mobile phase: Prepare as directed in the Assay.

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

Sample solution: Pass a portion of the solution under test through a suitable PVDF filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 285 nm

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

Flow rate: 1 mL/min

Injection volume: 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

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 from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of the Standard

V = volume of Medium, 1000 mL

L = label claim (mg/Capsule)

Tolerances: NLT 70% (Q) of the labeled amount of fenofibrate (C₂₀H₂₁CIO₄) is dissolved.

4.1.2 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

Standard solution: (L/1000) mg/mL of USP Fenofibrate RS in Medium, where L is the label claim in mg/Capsule. 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.

Blank: Medium

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: Spectrophotometry

Detector: UV 288 nm

Path length: 0.1-cm flow cell

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 (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, 900 mL

L= label claim (mg/Capsule)

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

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

Medium: 0.72% sodium dodecyl sulfate (RB 1-May-2021) 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 label claim in mg/Capsule. 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-um pore size. Dilute with Medium, if necessary.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: Spectrophotometry

Detector: UV 290 nm

Blank: Medium

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 D x V 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)

D = dilution factor for the Sample solution

V = volume of Medium, 1000 mL

L = label claim (mg/Capsule)

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

4.1.4 Test 4: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4

Medium: 0.05 M sodium dodecyl sulfate (RB 1-May-2021) in water, 1000 mL

Apparatus 2: 75 rpm, with helix sinkers or hose clamp sinkers

Times: 30 min for products labeled to contain 67, 134, and 200 mg; 40 min for products labeled to contain 43 and 130 mg

Standard stock solution: 0.5 mg/mL of USP Fenofibrate RS in Medium prepared as follows. Dissolve a suitable quantity of USP Fenofibrate RS, taken in a suitable volumetric flask, in about 6% of the total volume of methanol, and dilute with Medium to volume.

Standard solution: Prepare solutions of USP Fenofibrate RS in Medium as per Table 1 from Standard stock solution.

Table 1

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first 3 mL of the filtrate.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: Spectrophotometry

Detector: UV 291 nm

Path length: 0.1-cm flow cell

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 (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

L = label claim (mg/Capsule)

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

4.1.5 Test 5: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 5

Medium: 0.025 Msodium dodecyl sulfate (RB 1-May-2021) in water; 1000 mL, deaerated

Apparatus 2: 75 rpm, with suitable sinkers

Time: 20 min

Standard stock solution: 0.5 mg/mL of USP Fenofibrate RS in methanol. Sonicate if necessary.

Standard solution: 12.5 µg/mL of USP Fenofibrate RS prepared by diluting quantitatively from Standard stock solution with Medium

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

Dilute quantitatively with Medium to the nominal concentration as per Table 2.

Table 2

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: Spectrophotometry

Detector: UV 290 nm

Blank: Medium

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/L) x D x V 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)

L = label claim (mg/Capsule)

D = dilution factor for the Sample solution

V = volume of Medium, 1000 mL

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

4.1.6 Test 6: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 6

Dissolution Test 6 is suitable for products labeled to contain 200 mg of fenofibrate.

Medium, Solution A, Mobile phase, and System suitability: Proceed as directed in Test 1.

Apparatus 2: 75 rpm, with suitable sinkers

Time: 60 min

Standard solution: 0.2 mg/mL of USP Fenofibrate RS prepared as follows. Transfer a suitable amount of USP Fenofibrate RS into a suitable volumetric flask. Add methanol to 2% of the total volume of the flask and sonicate to dissolve. 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. Discard the first few milliliters of filtrate.

Chromatographic system: Proceed as directed in Test 1 except for Run time.

Run time: NLT 2 times the retention time of the fenofibrate

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 USP Fenofibrate RS in the Standard solution (mg/mL)

V = volume of Medium, 1000 mL

L = label claim (mg/Capsule)

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

4.1.7 Test 7: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 7

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

Apparatus 2: 75 rpm

Time: 60 min

Buffer: 136 mg/L of potassium phosphate, monobasic in water. Adjust with dilute phosphoric acid (1:10, v/v) to a pH of 2.9 ± 0.05.

Mobile phase: Methanol and Buffer (80:20)

Standard solution: (L/1000) mg/mL of USP Fenofibrate RS in Mobile phase, where L is the label claim in mg/Capsule. Sonicate if necessary.

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

Flow rate: 1 mL/min

Injection volume: 10 µL for Capsules labeled to contain 67 mg; 5 µL for Capsules labeled to contain 134 or 200 mg

Run time: NLT 1.5 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 USP Fenofibrate RS in the Standard solution (mg/mL)

V = volume of Medium, 1000 mL

L label claim (mg/Capsule)

Tolerances: NLT 80% (Q) of the labeled amount of fenofibrate (C₂₀H₂₁CIO₄) is dissolved. (RB 1-May-2021)

4.2 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, and stir for 15 min. Dilute with methanol to volume to obtain a solution having a known concentration of about 0.4-0.7 mg/mL of fenofibrate, based on the label claim.

Sample solution: Nominally 60-70 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.

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

Use Sample solution 2 for Capsules labeled to meet the requirements of Dissolution Test 2. For all other products, use Sample solution 1.

Solution A: 136 mg/L of potassium phosphate, monobasic (RB 1-May-2021) Adjust with dilute phosphoric acid (1 in 10) to a pH of 2.9 ± 0.05.

Mobile phase: Methanol and Solution A (4:1)

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

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

Sensitivity 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: Nominally 0.67 mg/mL of fenofibrate prepared as follows. 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.

Sample solution 2 (for Capsules labeled to meet the requirements of Dissolution Test 2): Nominally 0.67 mg/mL of fenofibrate prepared as follows. 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 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 1-2 mL.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 285 nm

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

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 3 times the retention time of the fenofibrate peak

System suitability

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

Suitability requirements

Resolution: NLT 3.0 between fenofibrate and 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, Sensitivity solution

Analysis

Samples: Standard solution and designated Sample solution

Calculate the percentage of fenofibrate related compound B in the portion of Capsules taken:

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

r_U = peak response of fenofibrate related compound B from the Sample solution

r_S = peak response of fenofibrate related compound B from the Standard solution

C_S = concentration of fenofibrate related compound B in the Standard solution (mg/mL)

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

Calculate the percentage of any unspecified impurity in the portion of Capsules taken:

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

r_U = peak response of each unspecified impurity from the Sample solution

r_S = peak response of fenofibrate from the Standard solution

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

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

Acceptance criteria

Individual impurities: NMT 0.5% for fenofibrate related compound B; NMT 0.2% for any other unspecified impurity

Total impurities: NMT 2.0%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

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

6.2 LABELING

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

6.3 USP REFERENCE STANDARDS (11)

USP Fenofibrate RS

USP Fenofibrate Related Compound B RS

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

C₁₇H₁₅CIO₄ 318.75