Niacin Extended-Release Tablets

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

Niacin Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of niacin (C₆H₅NO₂).

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.

3 ASSAY

Change to read:

PROCEDURE

Diluent: Methanol and water (82:18)

Mobile phase: Methanol and water (82:18), adjusted with glacial acetic acid to a pH of 3.15 ± 0.05

Standard solution: 250 µg/mL of USP Niacin RS, 50 µg/mL of USP 6-Hydroxynicotinic, 6-Hydroxynicotinic Acid RS, and 97.8 µg/mL of pyridine in Diluent

Sample solution: Transfer a quantity of powder, equivalent to 50 mg of niacin from NLT 20 finely powdered Tablets, to a suitable flask, add Diluent, and stir for 2 h. Dilute with Diluent to a final concentration of 250 µg/mL of niacin.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 260 nm

Column: 4.6-mm x 15-cm; 5-µm packing L8

Flow rate: 1.0 mL/min

Injection volume: 25 µL

System suitability

Sample: Standard solution

[NOTE-See

^▲Table 14 _{▲(RB 1-Aug-2020)} for relative

Suitability requirements

Resolution: NLT 1.5 between pyridine and 6-hydroxynicotinic acid, and NLT 1.5 between 6-hydroxynicotinic acid and niacin

Relative standard deviation: NMT 3.0% for each of the peaks

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of niacin (C₆H₅NO₂) in the portion of Tablets taken:

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

r_U = peak area of niacin from the Sample solution

r_S = peak area of niacin from the Standard solution

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

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

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711)

4.1.1 Test 1

Medium: Water, 900 mL

Apparatus 1: 100 rpm

Times: 1, 3, 6, 9, 12, and 20 h; without Medium replacement. [NOTE-Withdraw the same volume at each time point.]

Solution A: Solution of sodium heptanesulfonate in acetic acid, methanol, and water (4:44:33:19), w/w¹

Mobile phase: Mixture of methanol, water, and Solution A (560:440:25)

Standard solution: USP Niacin RS at a known concentration in water in the range of 75-750 µg/mL

Sample solution: Filtered portion of the solution under test suitably diluted with Medium if necessary

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm x 15-cm; 10-µm packing L1

Flow rate: 1.0 mL/min

Injection volume: 15 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

Determine, in mg/mL, the content of niacin (C₆H₅NO₂) in the Medium at each time point:

                         Result = (r_U/r_S) × C_S × D

r_U = peak area of niacin from the Sample solution

r_S = peak area of niacin from the Standard solution 

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

D = dilution factor for the Sample solution

Calculate the percentage of the labeled amount of niacin (C₆H₅NO₂) dissolved at each time point:

At 1 h:

                         Result₁ = (C₁ x V/L) x 100

At 3 h:

                         Result₂ = [C₂ x (V - V_S) + C₁ x V_S] x 100/L

At 6 h:

                         Result₃ = [C₃ x [V - 2 x V_S] + [(C₁ + C₂) x V_S] x 100/L

At 9 h:

                         Result₄ = [C₄ x [V - 3 x V_S] + [C₁ + C₂ +C₃) x V_S] x 100/L

At 12 h:

                         Result₅ = [C₅ x (V - 4 x V_S) + (C₁ + C₂ +C₃ + C₄) x V_S] x 100/L

At 20 h:

                         Result₆ = [C₆ x (V - 5 x V_S) + (C₁ + C₂ +C₃ + C₄ + C₅) × V_S]  ×100/L

C = as C₁, C_2,.... C₆ the content of niacin in the Medium at each time point (mg/mL)

V = volume of Medium, 900 mL

V_S = volume of sample withdrawn at each time point (mL)

L = label claim (mg/Tablet)

Tolerances: The percentage of the labeled amount of niacin (C₆H₅NO₂) dissolved at the times specified in Table 1. Table 2. and Table 3 conforms to Dissolution (711), Acceptance Table 2.

Table 1. For Tablets Labeled to Contain 500 mg or Less/Tablet

Table 2. For Tablets Labeled to Contain 750 mg/Tablet

Table 3. For Tablets Labeled to Contain 1000 mg/Tablet

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

Acid stage medium: 0.1 N hydrochloric acid; 900 mL

Buffer stage medium: 6.8 g of monobasic potassium phosphate and 0.89 g of sodium hydroxide pellets in 1000 mL of water. Adjust with diluted sodium hydroxide or phosphoric acid to a pH of 6.8; 900 mL..

Apparatus 1: 100 rpm

Times: 1, 4, 12, and 24 h: 1 and 4 h in the Acid stage medium; 12 and 24 h in the Buffer stage medium. Replace the volume withdrawn with the equal volume of medium preheated to 37 ± 0.5°.

Procedure: After 4 h replace the Acid stage medium with the Buffer stage medium, and run the test for the times specified (additional 20 h for a total of 24 h).

[NOTE-Withdraw the same volume at each time point. Pass a portion of the solution through a suitable filter.]

Standard stock solution: 0.2 mg/mL of USP Niacin RS in water

Standard solution 1: Dilute Standard stock solution with Acid stage medium to a final concentration of 0.01 mg/mL of USP Niacin RS.

Standard solution 2: Dilute Standard stock solution with Buffer stage medium to a final concentration of 0.01 mg/mL of USP Niacin RS.

Sample solution

For Tablets labeled to contain 500 mg: Dilute a filtered portion of the solution under test with appropriate dissolution medium 25-fold.

For Tablets labeled to contain 750 mg: Dilute a filtered portion of the solution under test with appropriate dissolution medium 33-fold.

For Tablets labeled to contain 1000 mg: Dilute a filtered portion of the solution under test with appropriate dissolution medium 50-fold.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 262 nm

Path length: 1 cm

Blank: Acid stage medium or Buffer stage medium

Analysis

Samples: Standard solution 1 or Standard solution 2 and Sample solution

Determine the concentration, in mg/mL, of niacin (C₆H₅NO₂) in the sample withdrawn from the vessel at each time point:

                         Result = [(A_U - A_B)/A_S] x C_S x D

A_U = absorbance of the Sample solution

A_B = absorbance of the Blank

A_S = absorbance of the Standard solution

C_S = concentration of USP Niacin RS in the Standard solution (mg/ml.)

D = dilution factor for the Sample solution

Calculate the percentage of the labeled amount of niacin (C₆H₅NO₂) dissolved at each time point:

At 1 h:

                         Result₁ = (C₁ x V) x 100

At 4 h:

                         Result₂ = [C₂ x V + C₁ x V_S] x 100/L

At 12 h:

                         Result₃ = [(C₃ + C₂) x V + C₁ x V_S] x 100/L

At 24 h:

                         Result₄ = [(C₄ + C₂) x V + (C₁ + C₃) x V_S] x 100/L

C = as C₁,... C₄ the content of niacin in the related dissolution medium at each time point (mg/mL)

V = volume of Medium, 900 mL

V_S = volume of sample withdrawn at each time point (mL)

L = label claim (mg/Tablet)

Tolerances: The percentage of the labeled amount of niacin (C₆H₅NO₂) dissolved at the times specified in Table 4 and Table 5 conforms to Dissolution (711), Acceptance Table 2.

Table 4. For Tablets Labeled to Contain 500 mg/Tablet

Table 5. For Tablets Labeled to Contain 750 and 1000 mg/Tablet

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

Medium: Water; 900 mL

Apparatus 1: 100 rpm

Times: 1, 3, 6, 9, 12, and 20 h; without Medium replacement

[NOTE-Withdraw the same volume at each time point. Pass a portion of the solution through a stainless steel filter.]

Solution A: 1 mg/mL of sodium 1-hexanesulfonate monohydrate in water

Mobile phase: Mixture of Solution A, methanol, and glacial acetic acid (840:150:10)

Standard solution: (L/900) mg/mL of USP Niacin RS in Medium, where L is the label claim in mg/Tablet

[NOTE-Use sonication for complete dissolution, if necessary.]

Sample solution: Filtered portion of the solution under test

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Sample cooler: 10°

Detector: UV 262 nm

Column: 3.9-mm × 15-cm; 10-µm packing L1

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 2 µL

System suitability

Sample: Standard solution

Suitability requirements

Theoretical plates: NLT 1000

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Determine the concentration, in mg/mL, of niacin (C₆H₅NO₂) in the Medium at each time point:

                         Result = (r_U/r_S) × C_S

r_U = peak area of niacin from the Sample solution

r_S = peak area of niacin from the Standard solution S

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

Calculate the percentage of the labeled amount of niacin (C₆H₅NO₂) dissolved at each time point:

At 1 h:

                         Result₁ = (C₁ x V/L) x 100

At 3 h:

                         Result₂ = [C₂ x (V - V_S) + C₁ x V_S] x 100/L

At 6 h:

                         Result₃ = [C₃ x (V - 2 x V_S)+(C₁+ C₂) × V_S] × 100/L

At 9 h:

                         Result₄ = [C₄ x (V - 3 × V_S) + (C₁+ C₂+ C₃ )× V_S]×100/L

At 12 h:

                         Result₅ = [C₅ x (V - 4 x V_S) + (C₁ + C₂ +C₃ + C₄) x V_S] x 100/L

At 20 h:

                         Result₆ = [C₆ x (V - 5 x V_S) + (C₁ + C₂ +C₃ + C₄ + C₅) × V_S]  ×100/L

C = as C₁, C_2,.... C₆ the content of niacin in the Medium at each time point (mg/mL)

V = volume of Medium, 900 mL

Vs = volume of sample withdrawn at each time point (mL)

L = label claim (mg/Tablet)

Tolerances: The percentage of the labeled amount of niacin (C₆H₅NO₂) dissolved at the times specified in Table 6 and Table Z conforms to Dissolution (711), Acceptance Table 2.

Table 6. For Tablets Labeled to Contain 500 and 1000 mg/Tablet

Table 7. For Tablets Labeled to Contain 750 mg/Tablet

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

Medium: Water; 900 mL

Apparatus 1: 100 rpm

Times: 1, 3, 6, 9, 12, and 24 h for Tablets labeled to contain 500 and 1000 mg/Tablet, and 1, 6, 12, and 24 h for Tablets labeled to contain 750 mg/Tablet; without Medium replacement

[NOTE-Withdraw the same volume at each time point. Pass a portion of the solution through a 0.45-µm PVDF membrane filter, discarding the first 2 mL of the filtrate.]

Standard stock solution: 0.5 mg/mL of USP Niacin RS in water

Standard solution: Dilute Standard stock solution with Medium to a final concentration of 0.02 mg/mL of USP Niacin RS.

Sample solution

For Tablets labeled to contain 500 mg: Dilute a filtered portion of the solution under test with Medium 25-fold.

For Tablets labeled to contain 750 mg: Dilute a filtered portion of the solution under test with Medium 40-fold.

For Tablets labeled to contain 1000 mg: Dilute a filtered portion of the solution under test with Medium 50-fold.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 262 nm

Path length: 1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Determine the concentration, in mg/mL, of niacin (C₆H₅NO₂) in the sample withdrawn from the vessel at each time point:

                         Result = [(A_U/A_B)/A_S] × C_S × D

A_U = absorbance of the Sample solution

A_B = absorbance of the Blank

A_S= absorbance of the Standard solution

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

D = dilution factor for the Sample solution

For Tablets labeled to contain 500 and 1000 mg: Calculate the percentage of the labeled amount of niacin (C₆H₅NO₂) dissolved at each

time point:

At 1 h:

                         Result₁ = (C₁ x V/L) x 100

At 3 h:

                         Result₂ = [C₂ x (V - V_S) + C₁ x V_S] x 100/L

At 6 h:

                         Result₃ = [C₃ x (V - 2 x V_S) + (C₁+ C₂) × V_S] × 100/L

At 9 h:

                         Result₄ = [C₄ x (V - 3 × V_S) + (C₁+ C₂+ C₃ )× V_S]×100/L

At 12 h:

                         Result₃ = [C₃ x (V - 2 x V_S) + (C₁+ C₂) × V_S] × 100/L

At 24 h:

                         Result₆ = [C₆ x (V - 5 x V_S) + (C₁ + C₂ +C₃ + C₄ + C₅) × V_S]  ×100/L

For Tablets labeled to contain 750 mg:

Calculate the percentage of the labeled amount of niacin (C₆H₅NO₂) dissolved at each time point:

At 1 h:

                         Result₁ = (C₁ x V/L) x 100

At 6 h:

                         Result₂ = [C₂ x (V - V_S) + C₁ x V_S] x 100/L

At 12 h:

                         Result₃ = [C₃ x (V - 2 x V_S) + (C₁+ C₂) × V_S] × 100/L

At 24 h:

                         Result₄ = [C₄ x (V - 3 × V_S) + (C₁+ C₂+ C₃ )× V_S]×100/L

C = as C₁, C_2,.... C₆ the content of niacin in the Medium at each time point (mg/mL)

V = volume of Medium, 900 mL

V_S = volume of sample withdrawn at each time point (mL)

L = label claim (mg/Tablet)

Tolerances: The percentage of the labeled amount of niacin (C₆H₅NO₂) dissolved at the times specified in Table 8, Table 9, and Table 10 conforms to Dissolution (711), Acceptance Table 2.

Table 8. For Tablets Labeled to Contain 500 mg/Tablet

Table 9. For Tablets Labeled to Contain 750 mg/Tablet

Table 10. For Tablets Labeled to Contain 1000 mg/Tablet

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

Medium: Water, 900 mL

Apparatus 1: 100 rpm

Times: 1, 6, 12, and 24 h; without Medium replacement

[NOTE-Withdraw the same volume at each time point. Pass a portion of the solution through a 0.45-µm nylon membrane filter, discarding the first 2 mL of the filtrate.]

Solution A: 1.1 mg/mL of sodium 1-heptanesulfonate in water

Mobile phase: Mixture of Solution A and methanol (70:30)

Standard solution: 0.84 mg/mL of USP Niacin RS in water

[NOTE-Use sonication for complete dissolution, if necessary.)

Sample solution: Filtered portion of the solution under test

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 262 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1.0 mL/min

Injection volume: 5 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

Determine the concentration, in mg/mL, of niacin (C₆H₅NO₂) in the Medium at each time point:

                         Result = (r_U/r_S) × C_S

r_U = peak area of niacin from the Sample solution

r_S = peak area of niacin from the Standard solution s

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

Calculate the percentage of the labeled amount of niacin (C₆H₅NO₂) dissolved at each time point:

At 1 h:

                         Result₁ = (C₁ x V/L) x 100

At 6 h:

                         Result₂ = [C₂ x (V - V_S) + C₁ x V_S] x 100/L

At 12 h:

                         Result₃ = [C₃ x (V - 2 x V_S) + (C₁+ C₂) × V_S] × 100/L

At 24 h:

                         Result₄ = [C₄ x (V - 3 × V_S) + (C₁+ C₂+ C₃ )× V_S]×100/L

C = as C₁, C_2,.... C₄ the content of niacin in the Medium at each time point (mg/mL)

V volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of sample withdrawn at each time point (mL)

Tolerances: The percentage of the labeled amount of niacin (C₆H₅NO₂) dissolved at the times specified in Table 11 and Table 12 conforms to Dissolution (711), Acceptance Table 2.

Table 11. For Tablets Labeled to Contain 500 mg/Tablet

Table 12. For Tablets Labeled to Contain 1000 mg/Tablet

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

Medium: Water, 900 mL

Apparatus 1: 100 rpm

Times: 1, 6, 12, and 24 h. Replace the volume withdrawn with the equal volume of Medium preheated to 37 ± 0.5"

[NOTE-Withdraw the same volume at each time point. Pass a portion of the solution through a 0.45-µm nylon or PVDF membrane filter.]

Standard stock solution: 0.44 mg/mL of USP Niacin RS in water

[NOTE-Use sonication for complete dissolution, if necessary.]

Standard solution: Dilute the Standard stock solution with Medium to a final concentration of 0.026 mg/mL of USP Niacin RS.

Sample solution

For Tablets labeled to contain 500 mg: Dilute a filtered portion of the solution under test with dissolution medium 20-fold.

For Tablets labeled to contain 750 mg: Dilute a filtered portion of the solution under test with dissolution medium 33-fold.

For Tablets labeled to contain 1000 mg: Dilute a filtered portion of the solution under test with dissolution medium 40-fold.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 262 nm

Path length: 1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Determine the concentration, in mg/mL, of niacin (C₆H₅NO₂) in the sample withdrawn from the vessel at each time point:

                         Result = [(A_U/A_B)/A_S] × C_S × D

A_U = absorbance of the Sample solution

A_B = absorbance of the Blank 

A_S = absorbance of the Standard solution

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

D = dilution factor for the Sample solution

Calculate the percentage of the labeled amount of niacin (C₆H₅NO₂) dissolved at each time point:

At 1 h:

                         Result₁ = (C₁ x V/L) x 100

At 6 h:

                         Result₂ = [C₂ x V + C₁ x V_S] x 100/L

At 12 h:

                         Result₃ = [C₃ x V + (C₁+ C₂) × V_S] × 100/L

At 24 h:

                         Result₄ = [C₄ x V + (C₁+ C₂+ C₃ ) × V_S]×100/L

C = as C₁, C_2,.... C₄ concentration of niacin in the dissolution medium at each time point (mg/mL)

V = volume of Medium, 900 mL

V_S = volume of the sample withdrawn from the vessel and replaced at each time point (mL) S

L = label claim (mg/Tablet)

Tolerances: The percentage of the labeled amount of niacin (CHNO₂) dissolved at the times specified in Table 13 conforms to Dissolution (711), Acceptance Table 2.

Table 13. For Tablets Labeled to Contain 500, 750, and 1000 mg/Tablet

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

Diluent, Mobile phase, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of 6-hydroxynicotinic acid or pyridine in the portion of Tablets taken:

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

r_U = peak area of 6-hydroxynicotinic acid or pyridine from the Sample solution

r_S = peak area of 6-hydroxynicotinic acid or pyridine from the Standard solution

C_S = concentration of USP 6-Hydroxynicotinic Acid RS or pyridine in the Standard solution (µg/mL)

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

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

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

r_U = peak area of each impurity from the Sample solution

r_S = peak area of niacin from the Standard solution

C_S = concentration of USP Niacin RS in the Standard solution (µg/mL)

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

Acceptance criteria: See Table ^▲14._{▲(RB 1-Aug-2020)}

Table ^▲14._{▲(RB 1-Aug-2020)}

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

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

USP REFERENCE STANDARDS (11)

USP 6-Hydrozvnicotinic Acid RS

USP Niacin RS