Nifedipine 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)

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1 DEFINITION

Nifedipine Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆). [NOTE-Nifedipine, when exposed to daylight and certain wavelengths of artificial light, readily converts to a nitrosophenylpyridine derivative. Exposure to UV light leads to the formation of a nitrophenylpyridine derivative. Perform assays and tests in the dark or under golden fluorescent or other low-actinic light. Use low-actinic glassware.]

2 IDENTIFICATION

A. The retention time of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 197U

Standard stock solution and Sample stock solution: Prepare as directed in the Assay.

Standard solution: 0.02 mg/mL of USP Nifedipine RS in Mobile phase from the Standard stock solution

Sample solution: Nominally 0.02 mg/mL of nifedipine in Mobile phase from the Sample stock solution

3 ASSAY

PROCEDURE

[NOTE-Conduct the Assay promptly after preparation of the Standard solution and the Sample solution.]

Mobile phase: Acetonitrile, methanol, and water (25:25:50)

Standard stock solution: 1 mg/mL of USP Nifedipine RS in methanol

Standard solution: 0.1 mg/mL of USP Nifedipine RS from the Standard stock solution in Mobile phase

Sample stock solution: Dissolve an amount equivalent to 420 mg of nifedipine from powdered Tablets in 130 mL of water in a 250-mL volumetric flask; or transfer the intact Tablets to a 400-mL, high-speed blender cup containing 130 mL of water. Homogenize until a uniform suspension is achieved (about 2 min), and transfer the suspension with the aid of a mixture of acetonitrile and methanol (1:1) to a 250-mL volumetric flask. Dilute with a mixture of acetonitrile and methanol (1:1) to volume, and stir for 30 min. Centrifuge the resulting suspension to obtain a clear supernatant.

Sample solution: Nominally 0.1 mg/mL of nifedipine prepared as follows. Transfer 3.0 mL of the Sample stock solution to a 50-mL volumetric flask, dilute with Mobile phase to volume, and filter. [NOTE-Reserve a portion of this solution for use as the Sample solution in the test for Organic Impurities.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 265 nm

Columns

Guard: 2.1-mm x 3-cm; packing L1

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

Flow rate: 1 mL/min

Injection volume: 25 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 4000 theoretical plates

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) in the portion of Tablets taken: 

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

C_U = nominal concentration of nifedipine 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: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 1

Medium: Water: 50 mL

Apparatus 7: (See Drug Release (724).) 15-30 cycles/min. Do not use the reciprocating disk; use a 25-cm Plexiglas rod, the perimeter of the Tablets being affixed to the rod with a water-insoluble glue. The solution containers are 25-mm test tubes, 150-200 mm in length, and the water bath is maintained at 37 ± 0.5°. At the end of each specified test interval, the systems are transferred to the next row of new test tubes containing 50 mL of fresh Medium.

Times: 4, 8, 12, 16, 20, and 24 h

Diluent: Methanol and water (1:1)

Standard solution: Transfer 50 mg of USP Nifedipine RS to a 100-mL volumetric flask. Dissolve in 50 mL of methanol, and dilute with water to volume. Quantitatively dilute this solution with Diluent to obtain solutions having suitable known concentrations.

Sample solution: Use portions of the solution under test, passed through a suitable filter of 0.4-um pore size, suitably diluted with methanol, and stepwise if necessary, with Diluent to obtain a final mixture consisting of equal parts of methanol and water.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 338 nm

Cell: 0.5 cm

Analysis: Determine the amount of nifedipine (C₁₇H₁₈N₂O₆) released in the Sample solution at each 4-h interval from UV absorbances. [NOTE-For the 4-h time period, determine the absorbance at 456 nm, and use this determination to correct for excipient interference.]

Tolerances: See Table 1.

Table 1

^a The amount dissolved is expressed in terms of the labeled Tablet strength rather than in terms of the labeled total contents.

The cumulative percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆), released at the times specified, conform to Dissolution (711), Acceptance Table 2.

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

Solution A: Dissolve 330.9 g of dibasic sodium phosphate and 38 g of citric acid in water in a 1-L volumetric flask. Add 10 mL of phosphoric acid, and dilute with water to volume.

Medium: Mix 125.0 mL of Solution A and 1 L of 10% sodium dodecyl sulfate solution, and dilute to 10 L. Adjust, if necessary, to a pH of 6.8; 900 mL.

Apparatus 2: 50 rpm, with sinkers (see Dissolution (711), Figure 2a)

Times: 3, 6, and 12 h

Mobile phase: Acetonitrile and water (7:3)

Standard stock solution: 1.11 mg/mL of USP Nifedipine RS in methanol

Standard solution: 0.1 mg/mL of USP Nifedipine RS from the Standard stock solution in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 350 nm

Column: 4.0-mm x 125-mm; 3-µm packing L1

Temperature: 40°

Flow rate: 1.5 ml/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 2000 theoretical plates

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Determine the amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved.

Tolerances: See Table 2.

Table 2

The percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆), dissolved at the times specified, conform to Dissolution (711). Acceptance Table 2.

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

4.1.3.1 For Tablets labeled to contain 30 mg of nifedipine: Phase 1

Medium: 0.05 M phosphate buffer, pH 7.5; 900 mL

Apparatus 2: 100 rpm

Time: 1 h

Standard solution: 0.034 mg/mL of USP Nifedipine RS in Medium. [NOTE-If necessary, a volume of methanol, not exceeding 10% of the final volume, can be used to help solubilize nifedipine.]

Sample solution: Pass a portion of the solution under test through a suitable filter.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 238 nm

Cell: 0.5 cm

Analysis: (NOTE-After the run, take the Tablet out of the dissolution vessel, adapt a sinker to it, and transfer the Tablet with the sinker to the dissolution vessel containing the Medium for Phase 2.] Determine the amount of nifedipine (C₁₇H₁₈N₂O₆) released in Phase 1, using filtered portions of the Sample solution, in comparison with the Standard solution, using the Medium as the blank.

4.1.3.2 For Tablets labeled to contain 30 mg of nifedipine: Phase 2

Medium: 0.5% sodium dodecyl sulfate in simulated gastric fluid without enzyme, pH 1.2; 900 mL

Apparatus 2: 100 rpm

Times: 1, 4, 8, and 12 h

Standard solution: 0.034 mg/mL of USP Nifedipine RS in Medium. [NOTE-If necessary, a volume of methanol, not exceeding 10% of the final volume, can be used to help solubilize nifedipine.]

Sample solution: Pass a portion of the solution under test through a suitable filter.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 238 nm

Analysis: Determine the amount of nifedipine (C₁₇H₁₈N₂O₆) released in Phase 2, using filtered portions of the Sample solution, in comparison with the Standard solution, using Medium as the blank.

Tolerances: See Table 3.

Table 3

^a For each dosage unit, add the amount dissolved in phosphate buffer, pH 7.5 from Phase 1 to the amount dissolved at each time point in Phase 2.

The cumulative percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆), dissolved at the times specified, conform to Dissolution (711), Acceptance Table 2.

4.1.3.3 For Tablets labeled to contain 60 mg of nifedipine: Phase 1

Medium: 0.05 M phosphate buffer, pH 7.5; 900 mL

Apparatus 2: 100 rpm

Time: 25 min

Standard solution: 0.067 mg/mL of USP Nifedipine RS in Medium. [NOTE-If necessary, a volume of methanol, not exceeding 10% of the final volume, can be used to help solubilize nifedipine.]

Sample solution: Pass a portion of the solution under test through a suitable filter.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 238 nm

Analysis: [NOTE-After the run, take the Tablet out of the dissolution vessel, adapt a sinker to it, and transfer the Tablet with the sinker to the dissolution vessel containing the Medium for Phase 2.] Determine the amount of nifedipine (C₁₇H₁₈N₂O₆) released in Phase 1, using filtered portions of the Sample solution, in comparison with the Standard solution, using the Medium as the blank.

4.1.3.4 For Tablets labeled to contain 60 mg of nifedipine: Phase 2

Medium: 0.5% sodium dodecyl sulfate in simulated gastric fluid without enzyme, pH 1.2; 900 mL

Apparatus 2: 100 rpm

Times: 1, 4, 8, and 12 h

Standard solution: 0.067 mg/mL of USP Nifedipine RS in Medium. [NOTE-If necessary, a volume of methanol, not exceeding 10% of the final volume, can be used to help solubilize nifedipine.]

Sample solution: Pass a portion of the solution under test through a suitable filter.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 238 nm

Analysis: Determine the amount of nifedipine (C₁₇H₁₈N₂O₆) released in Phase 2, using filtered portions of the Sample solution, in comparison with the Standard solution, using the Medium as the blank.

Tolerances: See Table 4.

Table 4

^a For each dosage unit, add the amount dissolved in phosphate buffer, pH 7.5 from Phase 1 to the amount dissolved at each time point in Phase 2.

The cumulative percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆), released in vivo and dissolved at the times specified, conform to Dissolution (711), Acceptance Table 2.

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

Medium: 0.5% sodium dodecyl sulfate in simulated gastric fluid without enzyme, pH 1.2; 900 mL

Apparatus 2: 100 rpm

Times: 1, 4, and 12 h

Standard solution: 0.067 mg/mL of USP Nifedipine RS for Tablets labeled to contain 60 mg, and 0.034 mg/ml. of USP Nifedipine RS for Tablets labeled to contain 30 mg, in Medium. [NOTE-If necessary, a volume of methanol, not exceeding 10% of the final volume, can be used to help solubilize nifedipine.]

Sample solution: Pass a portion of the solution under test through a suitable filter.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: UV 238 nm

Cell: 1 cm

Analysis: Determine the amount of nifedipine (C₁₇H₁₈N₂O₆) released, using filtered portions of the Sample solution, in comparison with the Standard solution, using the Medium as the blank.

Tolerances: See Table 5 and Table 6.

Table 5. For Tablets Labeled to Contain 30 mg of Nifedipine

Table 6. For Tablets Labeled to Contain 60 mg of Nifedipine

The cumulative percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆), released at the times specified, conform to Dissolution (711). Acceptance Table 2.

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

Medium: Water: 50 mL

Apparatus 7: (See Drug Release (724).) Use a 25-cm Plexiglas rod, the perimeter of the Tablets being affixed to the rod with a water-insoluble glue; 30 dips/min. The solution containers are 25-mm test tubes, 150-200 mm in length, and the water bath is maintained at 37 ±0.5°.

Times: 4, 12, and 24 h

Diluent A: Methanol and acetonitrile (1:1)

Diluent B: Diluent A and water (1:1)

Standard stock solution: 0.50 mg/mL of USP Nifedipine RS prepared as follows. Transfer a suitable amount of USP Nifedipine RS to an appropriate volumetric flask. Dissolve in 50% of the flask volume of Diluent A. Dilute with water to volume.

Standard solutions: 0.01, 0.05, and 0.20 mg/mL solutions, from the Standard stock solution in Diluent B, that are used at 4-, 12-, and 24-h samplings

Sample solution: Pass a portion of the solution under test through a suitable filter.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 338 nm

Cell: 0.5 cm

Analysis: (NOTE-For the 4-h time period, filter the solution under test, and determine the absorbance at 456 nm. Use this absorbance value to correct for excipient interference at the other time points.] Determine the amount of nifedipine released at each interval on portions of the Sample solution passed through a suitable filter of 0.45-µm pore size, suitably diluted, if necessary, with Diluent A and water to obtain a final mixture of water, methanol, and acetonitrile (2:1:1), in comparison with the appropriate Standard solution, using Diluent B as the blank.

Tolerances: See Table 7.

Table 7

The cumulative percentages of the labeled amount of nifedipine, dissolved at the times specified, conform to Dissolution (711), Acceptance Table 2.

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

Medium: Simulated gastric fluid without enzyme containing 0.5% of sodium dodecyl sulfate, pH 1.2; 900 mL, deaerated

Apparatus 1: 100 rpm

Times: 1, 4, and 12 h

Standard stock solution: 0.33 mg/mL of USP Nifedipine RS in methanol

Standard solution: Quantitatively dilute the Standard stock solution with Medium to obtain a solution having a concentration of about 0.033 mg/mL.

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

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 329 nm

Cell: 0.5 cm

Blank: Medium

Tolerances: See Table 8.

Table 8

The cumulative percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

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

Medium: Simulated gastric fluid without enzyme containing 0.5% sodium dodecyl sulfate, pH 1.2; 900 mL

Apparatus 2: 100 rpm, with three-prong sinker

Times: 1, 4, and 12 h

Standard solution: (L/900) mg/mL of USP Nifedipine RS in Medium, where L is the label claim, in mg/Tablet, of nifedipine. A small amount of methanol, not exceeding 6%-7% of the final volume of the first dilution, can be used to solubilize nifedipine.

Sample solution: Pass a portion of the solution under test through a suitable filter.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 238 nm

Cell: 1 mm, flow cell

Blank: Medium

Tolerances: See Table 9.

Table 9

The cumulative percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at the times specified conform to Dissolution (711). Acceptance Table 2.

4.1.8 Test 8: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 8

Acid stage medium: Simulated gastric fluid without enzyme containing 3% polysorbate 80, pH 1.2; 250 mL

Apparatus 3: 20 dpm, 20-mesh polypropylene screen on the bottom; 1 min drip time. The Tablet is automatically transferred by the apparatus to the next set of vessels for each time point.

Time: 1 h

Buffer stage medium: 0.01 M sodium phosphate buffer, pH 6.8, containing 3% Polysorbate 80 (dissolve 8.3 g of monobasic sodium phosphate and 1 g of sodium hydroxide in 6 L of water, adjust with either diluted sodium hydroxide or phosphoric acid to a pH of 6.8 ± 0.05, and add 180 g of polysorbate 80); 250 mL

Times: 2, 8, 12, and 24 h

Mobile phase: Acetonitrile, methanol, and water (35:35:30)

Standard stock solution: 1 mg/mL of USP Nifedipine RS in Buffer stage medium. An amount of methanol, about 40% of the final volume, can be used to dissolve nifedipine.

Standard solution: (L/1000) mg/mL in Buffer stage medium, from the 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.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 338 nm

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

Temperature: 30°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 4000 theoretical plates

Tailing factor: NMT 1.7

Relative standard deviation: NMT 2.0%

Analysis: Calculate the percentage of the labeled amount of nifedipine dissolved at each time point.

At 1 h:

                         D₁ = (r_U/r_S) × (C_S/L) × V × 100

At 2 h:

                          D = (r_U/r_S) × (C_S/L) × V × 100

                          D₂ = D₁ + D

At 8 h:

                          D = (r_U/r_S) × (C_S/L) × V × 100

                          D₈ = D₂ + D

At 12 h:

                          D = (r_U/r_S) × (C_S/L) × V × 100

                          D₁₂= D₈ + D

At 24 h:

                          D = (r_U/r_S) × (C_S/L) × V × 100

                          D₂₄ = D₁₂ + D

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)

L = label claim (mg/Tablet)

V = volume of Medium, 250 mL

Tolerances

Acid stage: NMT 5% of the labeled amount of nifedipine is dissolved in 1 h.

Buffer stage: See Table 10.

Table 10

The cumulative percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at the times specified conform to Dissolution (711). Acceptance Table 2.

4.1.9 Test 9: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 9

Medium: 0.03 M phosphate/citrate buffer, pH 6.8 with 1% sodium dodecyl sulfate (to a solution of 4.1 g/L of dibasic sodium phosphate and 0.475 g/L of citric acid monohydrate in water, add 10 g/L of sodium dodecyl sulfate. Adjust if necessary, with phosphoric acid to a pH of 6.8); 900 mL

Apparatus 2: 50 rpm, with a suitable sinker

Times: 3, 6, and 12 h

Standard stock solution: 0.33 mg/mL of USP Nifedipine RS in methanol

Standard solution: Prepare the corresponding USP Nifedipine RS solutions in Medium as directed in Table 11.

Table 11

Sample solution: Pass a portion of the solution under test at each time point through a suitable filter.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 346 nm

Cell: 1 cm

Blank: Medium

Analysis

Samples: Standard solutions and Sample solution Calculate the concentration (C_i) of nifedipine (C₁₇H₁₈N₂O₆) in the sample withdrawn from the vessel at each time point (i):

                         Result = (A_U/A_S) × C_S

A_U = absorbance of the Sample solution at each time point

A_S = absorbance of the Standard solution

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

Calculate the percentage of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at each time point (1):

                         Result₁ = C₁ x V x (1/L) x 100

                         Result₂ = {[C₂ x (V - V_S)] + (C₁ x V_S)} x (1/L) x 100

                         Result₃ = ({C₃ x [V - (2 x V_S)]} + [(C₂ + C₁) x V_S]) x (1/L) x 100

C_i = concentration of nifedipine in the Sample solution at the specified time point (i) (mg/mL) 

V = volume of the Medium, 900 mL

L = label claim (mg/Tablet)

Vs = volume of the Sample solution withdrawn at each time point (i) (mL) 

Tolerances: See Table 12.

Table 12

The percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

4.1.10 Test 10: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 10

Medium: pH 6.8 phosphate buffer with 0.5% sodium dodecyl sulfate (transfer 442.1 g of dibasic sodium phosphate and 38 g of citric acid in a 1-L volumetric flask. Add water to dissolve, add 10 mL of phosphoric acid, and dilute with water to volume. Transfer 60 g of sodium dodecyl sulfate to a suitable container. Add 150 mL of the phosphate solution above and 11,850 mL of water. Mix well and adjust with phosphoric acid or sodium hydroxide to a pH of 6.8); 900 mL

Apparatus 2: 50 rpm, with sinkers (see Dissolution (711), Figure 2a)

Times: 2, 8, and 16 h

Mobile phase: Methanol and water (60:40)

Standard solution: 0.06 mg/mL of USP Nifedipine RS prepared as follows. Transfer 12 mg of USP Nifedipine RS into a 200-mL volumetric flask. Add 20 mL of methanol, and dilute with Medium to volume. [NOTE-Sonication may be needed to aid dissolution.]

Sample solution: Withdraw a 10-mL aliquot at each time point. Pass a portion of the solution under test through a suitable filter.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 380 nm

Column: 4.6-mm x 7.5-mm; 3.5-µm packing L60

Temperature: 45°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 3000 theoretical plates

Tailing factor: NMT 1.5

Relative standard deviation: NMT 3.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of nifedipine (C₁₇H₁₈N₂O₆) in the sample withdrawn from the vessel at each time point (i):

                         Result = (r_U/r_S) × C_S

r_U = peak response of nifedipine in the Sample solution at each time point

r_S = peak response of nifedipine in the Standard solution S

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

Calculate the percentage of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at each time point (1):

                         Result₁ = C₁ x V x (1/L) x 100

                         Result₂ = {[C₂ x (V - V_S)] + (C₁ x V_S)} x (1/L) x 100

                         Result₃ = {(C₃ x [V - (2 x V_S)]} + [(C₂ + C₁) x V_S]) x (1/L) x 100

C_i = concentration of nifedipine in the Sample solution at the specified time point (1) (mg/mL)

V = volume of the Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point (i) (mL)

Tolerances: See Table 13.

Table 13

The percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

4.1.11 Test 11: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 11

Medium: 1.25% sodium dodecyl sulfate in water (transfer 12.5 g of sodium dodecyl sulfate to 1 L of water); 900 mL

Apparatus 2: 100 rpm

Times: 1, 2, 4, and 10 h

Standard solution: 0.033 mg/mL of USP Nifedipine RS for Tablets labeled to contain 30 mg prepared as follows. Transfer an appropriate amount of USP Nifedipine RS into a suitable volumetric flask. Add methanol to 1% volume of the flask, and dilute with Medium to volume.

[NOTE-Sonication may be needed to aid the dissolution.]

Sample solution: A portion of the solution under test at the time points specified

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelengths: 230-246 nm, from the difference between first derivative values at the wavelengths of maximum and minimum in the wavelength range from 230 to 246 nm

Cell: 1 mm

Blank: Medium

Analysis: Use an automatic dissolution system with an appropriate dissolution software. Determine the amount of nifedipine (CHN₂O) dissolved, using portions of the Sample solution, in comparison with the Standard solution.

Tolerances: See Table 14.

Table 14. For Tablets Labeled to Contain 30 mg of Nifedipine

The cumulative percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆), dissolved at the times specified, conform to Dissolution (711). Acceptance Table 2.

4.1.12 Test 12: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 12

Medium: pH 6.8 phosphate buffer with 1.25% sodium dodecyl sulfate (transfer 6 g of monobasic sodium phosphate and 112 mL of 0.2 N sodium hydroxide in a 1-L volumetric flask containing 800 mL of water. Mix to dissolve, and dilute with water to volume. Adjust with phosphoric acid or sodium hydroxide to a pH of 6.8. Transfer 12.5 g of sodium dodecyl sulfate in 1 L of the phosphate solution); 900 mL

Apparatus 2: 50 rpm

Times: 2, 6, 8, and 16 h

Standard solution: 0.067 mg/mL of USP Nifedipine RS for Tablets labeled to contain 60 mg prepared as follows. Transfer an appropriate amount of USP Nifedipine RS into a suitable volumetric flask. Add methanol to 1% volume of the flask, and dilute with Medium to volume.

[NOTE-Sonication may be needed to aid the dissolution.]

Sample solution: A portion of the solution under test at the time points specified

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelengths: 230-246 nm, from the difference between first derivative values at the wavelengths of maximum and minimum in the wavelength range from 230 to 246 nm

Cell: 1 mm

Blank: Medium

Analysis: Use an automatic dissolution system with an appropriate dissolution software. Determine the amount of nifedipine (CHN₂O) dissolved, using portions of the Sample solution, in comparison with the Standard solution.

Tolerances: See Table 15.

Table 15. For Tablets Labeled to Contain 60 mg of Nifedipine

The cumulative percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆), dissolved at the times specified, conform to Dissolution (711), Acceptance Table 2.

4.1.13 Test 13: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 13

Medium: 0.5% sodium dodecyl sulfate in simulated gastric fluid without enzyme, pH 1.2; 900 mL

Apparatus 2: 100 rpm, with suitable sinkers

Times

For Tablets labeled to contain 30 and 60 mg of nifedipine: 1, 4, 6, and 10 h

For Tablets labeled to contain 90 mg of nifedipine: 1, 4, 6, and 12 h

Mobile phase: Acetonitrile, methanol, water, and phosphoric acid (25:30:45:0.1)

Standard stock solution: 1.68 mg/mL of USP Nifedipine RS in methanol

Standard solution: A known concentration of USP Nifedipine RS in Medium from Standard stock solution, prepared as directed in Table 16

Table 16

Sample solution: At each specified time point, withdraw a 10-mL aliquot and replace with the same volume of Medium. Pass a portion of the solution under test through a suitable filter and discard the first few milliliters of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 338 nm

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

Flow rate: 2.0 mL/min

Injection volume: 20 µL

Run time: NLT 1.6 times the retention time of nifedipine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of nifedipine (C₁₇H₁₈N₂O₆) in the sample withdrawn from the vessel at each time point (i):

                         Result = (r_U/r_S) × C_S

r_U = peak response of nifedipine in the Sample solution at each time point

r_S = peak response of nifedipine in the Standard solution

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

Calculate the percentage of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at each time point (i): 

                         Result₁ = C₁ x V x (1/L) x 100

                         Result₂ = [(C₂ x V)+ (C₁ x V_S)] x (1/L) x 100

                         Result₃ = {(C₃ x V) + [(C₂ + C₁) x V_S]} x (1/L) x 100

                         Result₄ = {(C₄ x V) + [(C₃ + C₂ + C₁) x V_S]} x (1/L) x 100

C_i = concentration of nifedipine in the Sample solution at the specified time point (i) (mg/mL)

V = volume of the Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point (1) (mL)

Tolerances: See Table 17 and Table 18.

Table 17. For Tablets Labeled to Contain 30 and 60 mg of Nifedipine

Table 18. For Tablets Labeled to Contain 90 mg of Nifedipine

The percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

4.1.14 Test 15: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 15

Medium: pH 6.8 phosphate buffer with 0.5% sodium dodecyl sulfate (transfer 7.8 g of sodium phosphate monobasic dihydrate and 0.9 g of sodium hydroxide in 1 L of water. Adjust with 1 N sodium hydroxide or phosphoric acid to a pH of 6.8. Transfer 5 g of sodium dodecyl sulfate in 1 L of the phosphate solution); 900 mL

Apparatus 2: 50 rpm, with suitable sinkers

Times: 2, 8, 12, and 24 h

Mobile phase: Methanol and water (60:40)

Standard solution: 0.06 mg/mL of USP Nifedipine RS for Tablets labeled to contain 60 or 90 mg, and 0.03 mg/mL of USP Nifedipine RS for Tablets labeled to contain 30 mg, in Medium.

[NOTE-If necessary, a volume of methanol, not exceeding 10% of the final volume, can be used to help solubilize nifedipine.]

Sample solution: At each specified time point, withdraw a 10-mL aliquot. Pass a portion of the solution under test through a suitable filter of 0.45-um pore size, discarding the first 2-3 mL of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 380 nm

Column: 4.6-mm x 7.5-cm, 3.5 µm packing L60

Temperature: 45°

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of nifedipine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 3.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of nifedipine (C₁₇H₁₈N₂O₆) in the sample withdrawn from the vessel at each time point (i):

                         Result = (r_U/r_S) × C_S

r_U = peak response of nifedipine in the Sample solution at each time point 

r_S = peak response of nifedipine in the Standard solution

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

Calculate the percentage of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at each time point (1):

                         Result₁ = C₁ x V x (1/L) x 100

                         Result₂ = {[C₂ x (V - V_S)] + (C₁ x V_S)} x (1/L) x 100

                         Result₃ = {(C₃ x [V - (2 x V_S)]} + [(C₂ + C₁) x V_S]) x (1/L) x 100

                         Result₄ = ({C₄ x [V - (3 x V_S)] + [(C₃ + C₂ + C₁) x V_S) x (1/L) x 100

C_i = concentration of nifedipine in the Sample solution at the specified time point (i) (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point (i) (mL)

Tolerances: See Table 19.

Table 19.

The percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

4.1.15 Test 16: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 16

Medium: pH 6.8 phosphate buffer with 1.0% sodium dodecyl sulfate (add 10 g/L of sodium dodecyl sulfate to a solution of 4.1 g/L of anhydrous dibasic sodium phosphate, 0.13 mL/L of phosphoric acid and 0.475 g/L of anhydrous citric acid in water, adjust, if necessary, with phosphoric acid or sodium hydroxide to a pH of 6.8); 900 mL, deaerated

Apparatus 2: 50 rpm, with a suitable sinker

Times: 2, 8, 12 and 20 h

Mobile phase: Acetonitrile and water (50:50)

Standard stock solution: 1 mg/mL of USP Nifedipine RS in methanol

Standard solution: (L/900) mg/mL of USP Nifedipine RS in Medium, from the 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 at each time point.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 350 nm

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

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 25 µL

Run time: NLT 1.6 times the retention time of nifedipine

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 concentration (C_i) of nifedipine (C₁₇H₁₈N₂O₆) in the sample withdrawn from the vessel at each time point (i):

                         Result_i = (r_U/r_S) × C_S

r_U = peak response of nifedipine in the Sample solution

r_S = peak response of nifedipine in the Standard solution

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

Calculate the percentage of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at each time point (1):

                         Result₁ = C₁ x V x (1/L) x 100

                         Result₂ = {[C₂ x (V - V_S)] + (C₁ x V_S)} x (1/L) x 100

                         Result₃ = {(C₃ x [V - (2 x V_S)]} + [(C₂ + C₁) x V_S]) x (1/L) x 100

                         Result₄ = ({C₄ x [V - (3 x V_S)] + [(C₃ + C₂ + C₁) x V_S) x (1/L) x 100

C_i = concentration of nifedipine in the portion of sample withdrawn at each time point (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point (mL)

Tolerances: See Table 20.

Table 20

The percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at the times specified conform to Dissolution (711) Acceptance Table 2.

4.1.16 Test 17: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 17

Medium

For Tablets labeled to contain 30 mg or 60 mg of nifedipine: Simulated gastric fluid TS without enzyme. Adjust with hydrochloric acid or sodium hydroxide to a pH of 1.2. To this add 5 ml. of sodium dodecyl sulfate; 900 mL.

For Tablets labeled to contain 90 mg of nifedipine: Simulated gastric fluid TS without enzyme. Adjust with hydrochloric acid or sodium hydroxide to a pH of 1.2. To this add 1 mL of sodium dodecyl sulfate; 900 mL..

Apparatus 2: 100 rpm, with 3-prong sinkers

Times: 1, 6, and 14 h

Solution A: Add 1 mL of phosphoric acid to 1000 mL of water.

Mobile phase: Acetonitrile, methanol, and Solution A (25:25:50)

Standard stock solution: 0.33 mg/mL of USP Nifedipine RS prepared as follows. Transfer a suitable quantity of USP Nifedipine RS into an appropriate volumetric flask. Add 20% of the flask volume of methanol. Sonicate to dissolve, if necessary, and dilute with Medium to volume. Prepare the Standard solution immediately after preparation of the Standard stock solution.

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

Sample solution: At each specified time point, withdraw a known volume of the solution and replace with the same volume of Medium. Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 238 nm

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

Column temperature: 30°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: NLT 2.0 times the retention time of nifedipine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: 0.8-2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of nifedipine (C₁₇H₁₈N₂O₆) in the sample withdrawn from the vessel at each time point (i):

                         Result = (r_U/r_S) × C_S

r_U = peak response of nifedipine from the Sample solution at each time point

r_S = peak response of nifedipine from the Standard solution

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

Calculate the percentage of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at each time point (1):

                         Result₁ = C₁ x V x (1/L) x 100

                         Result₂ = [(C₂ x V)+ (C₁ x V_S)] x (1/L) x 100

                         Result₃ = {(C₃ x V) + [(C₂ + C₁) x V_S]} x (1/L) x 100

C_i = concentration of nifedipine in the portion of the Sample solution withdrawn at the time point (i) (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point and replaced with Medium (mL)

Tolerances: See Table 21.

Table 21

The percentages of the labeled amount of nifedipine (C,,H, N₂O) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

4.1.17 Test 18: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 18

Ensure that the laser hole of the Tablets are on the upper side during the drop of the Tablets into the dissolution apparatus.

Medium: Simulated gastric fluid TS without enzyme. Adjust with hydrochloric acid or sodium hydroxide to a pH of 1.2. To this add 5 mL of sodium dodecyl sulfate; 900 mL, deaerated, if necessary.

Apparatus 1: 100 rpm

Times: 4, 12, and 24 h

Mobile phase: Acetonitrile, methanol, and water (35:35:30)

Standard stock solution: 2.2 mg/mL of USP Nifedipine RS in methanol. Sonicate to dissolve.

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

Sample solution: At the times specified, withdraw a portion of the solution under test and replace with the same volume of Medium, Pass a portion of the solution under test through a suitable filter of 0.45-um pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 338 nm

Column: 4.6-mm x 25-cm, 5-um packing L1

Column temperature: 30°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: NLT 2.0 times the retention time of nifedipine

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 concentration (C_i) of nifedipine (C₁₇H₁₈N₂O₆) in the sample withdrawn from the vessel at each time point (i):

                         Result = (r_U/r_S) × C_S

r_U = peak response of nifedipine from the Sample solution at each time point

r_S = peak response of nifedipine from the Standard solution

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

Calculate the percentage of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at each time point (1):

                         Result₁ = C₁ x V x (1/L) x 100

                         Result₂ = [(C₂ x V)+ (C₁ x V_S)] x (1/L) x 100

                         Result₃ = {(C₃ x V) + [(C₂ + C₁) x V_S]} x (1/L) x 100

C_i = concentration of nifedipine in the portion of the Sample solution at the time point (i) (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time pointi and replaced with Medium (mL) 5

Tolerances: See Table 22.

Table 22

The percentages of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2-_{▲ (RB 1-Sep-2024)}

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

[NOTE-Conduct this test promptly after preparation of the Standard nifedipine solution and the Sample solution.]

Mobile phase: Acetonitrile, methanol, and water (25:25:50)

Quantitative limit stock solution A: 1 mg/mL of USP Nifedipine Nitrophenylpyridine Analog RS in methanol

Quantitative limit solution A: 6 µg/mL of USP Nifedipine Nitrophenylpyridine Analog RS from Quantitative limit stock solution A in Mobile phase

Quantitative limit stock solution B: 1 mg/mL of USP Nifedipine Nitrosophenylpyridine Analog RS in methanol

Quantitative limit solution B: 1.5 µg/mL of USP Nifedipine Nitrosophenylpyridine Analog RS from Quantitative limit stock solution B in Mobile phase

Standard nifedipine stock solution: 1 mg/mL of USP Nifedipine RS in methanol

Standard nifedipine solution: 0.3 mg/mL of USP Nifedipine RS from Standard nifedipine stock solution in Mobile phase

System suitability solution: Quantitative limit solution A, Quantitative limit solution B, and Standard nifedipine solution (1:1:1)

Standard solution: Mobile phase, Quantitative limit solution A, and Quantitative limit solution B (1:1:1)

[NOTE-Each mL of this solution contains about 2 µg of USP Nifedipine Nitrophenylpyridine Analog RS and 0.5 µg of USP Nifedipine Nitrosophenylpyridine Analog RS.]

Sample solution: Use a portion of the Sample solution prepared as directed in the Assay.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 265 nm

Columns

Guard: 2.1-mm x 3-cm; packing L1

Analytical: 4.6-mm x 25-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 25 µL

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 1.5 between the nitrophenylpyridine analog and nitrosophenylpyridine analog peaks; NLT 1.0 between the nitrosophenylpyridine analog and nifedipine peaks

Relative standard deviation: NMT 10% for each analog

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each analog in the portion of Tablets taken:

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

r_U = peak response of each analog from the Sample solution

r_S = peak response of each analog from the Standard solution

C_S = concentration of the appropriate analog USP Reference Standard in the Standard solution (µg/mL)

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

Acceptance criteria: NMT 2.0% of nifedipine nitrophenylpyridine analog and NMT 0.5% of nifedipine nitrosophenylpyridine analog, both relative to the nifedipine content

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers, and store at controlled room temperature.

LABELING: The labeling indicates the Dissolution test with which the product complies.

USP REFERENCE STANDARDS (11)

USP Nifedipine RS

USP Nifedipine Nitrophenvipyridine Analog RS

Dimethyl 4-(2-nitrophenyl)-2,6-dimethylpyridine-3,5-dicarboxylate.

C₁₇H₁₆N₂O₆       344.33

USP Nifedipine Nitrosophenylovridine Analog RS

Dimethyl 4-(2-nitrosophenyl)-2,6-dimethylpyridine-3,5-dicarboxylate.

C₁₇H₁₆N₂O₅          328.33