Nifedipine Capsules

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 Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆)

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

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A. ^▲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)}

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B. The retention time of the ^▲major peak of the _{▲(USP 1-May-2019)} Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

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PROCEDURE: Protect ^▲all solutions containing nifedipine_{▲(USP 1-May-2019)} from actinic light. 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 in Mobile phase from Standard stock solution

^▲Sample stock solution: Nominally 1 mg/mL of nifedipine prepared as follows. Transfer the contents of NLT 5 Capsules to a suitable volumetric flask. Dilute with methanol to volume._{▲(USP 1-May-2019)}

Sample solution: ^▲Nominally 0.1 mg/mL of nifedipine in Mobile phase from Sample stock solution. Pass through a suitable filter of 0.45-µm pore size_{▲(USP 1-May-2019)}

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 265 nm.

^▲For Identification A, use a diode array detector in the range of 200-400 nm._{▲(USP 1-May-2019)}

Columns

Guard: Packing L1

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

Flow rate: 1 mL/min

Injection volume: 25 µL

Run time: NLT 1.5 times the retention time of nifedipine _{▲(USP 1-May-2019)}

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 Capsules taken:

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

r_U = peak response of nifedipine from the Sample solution

r_S = peak response of nifedipine 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

4.1 DISSOLUTION (711)

Medium: Simulated gastric fluid TS (without pepsin); 900 mL

Apparatus 2: 50 rpm

Time: 20 min

Standard solution: Dissolve a quantity of USP Nifedipine RS in an amount of methanol not exceeding 2% of the final volume, and dilute with Medium to obtain a solution of a known suitable concentration.

Sample solution: Pass a portion of solution under test through a suitable filter, and dilute as needed with Medium, in comparison with the Standard solution. Filters must be checked for absorptive loss of nifedipine.

Instrumental conditions

Mode: UV

Analytical wavelength: 340 nm

Analysis

Samples: Standard solution and Sample solution

Determine the percentage of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) dissolved by using UV absorbances at the specified wavelength.

Tolerances: NLT 80% (Q) of the labeled amount of nifedipine (C₁₇H₁₈N₂O₆) is dissolved.

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4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements (USP 1-May-2019)

5 IMPURITIES

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ORGANIC IMPURITIES: Protect all solutions containing nifedipine (USP 1-May-2019) from actinic light. Conduct this test promptly after preparation of the Standard solution and the Sample solution.

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

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

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

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

Standard solution B: 6 µg/mL of USP Nifedipine Nitrophenylpyridine Analog RS in Mobile phase from Standard stock solution B

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

Standard solution C: 1.5 µg/mL of USP Nifedipine Nitrosophenylpyridine Analog RS in Mobile phase from Standard stock solution C

Standard solution D: Mixture of Standard solution B, Standard solution C, and Mobile phase (1:1:1)

System suitability solution: Mixture of Standard solution A, Standard solution B, and Standard solution C (1:1:1) ^▲_{▲(USP 1-May-2019)}

System suitability

Sample: System suitability solution

Suitability requirements

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

Relative standard deviation: NMT 10% for each nifedipine nitrophenylpyridine analog and nifedipine nitrosophenylpyridine analog

Analysis

Samples: Sample solution and Standard solution D

Calculate the percentage of nifedipine nitrophenylpyridine analog and nifedipine nitrosophenylpyridine analog in the portion of Capsules taken:

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

r_U = peak response of nifedipine nitrophenylpyridine analog or nifedipine nitrosophenylpyridine analog from the Sample solution

r_S = peak response of nifedipine nitrophenylpyridine analog or nifedipine nitrosophenylpyridine analog from Standard solution D

C_S = concentration of the appropriate USP Nifedipine Nitrophenylpyridine Analog RS or USP Nifedipine Nitrosophenylpyridine Analog RS in Standard solution D (mg/mL)

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

Acceptance criteria: See Table 1.

Table 1

6 ADDITIONAL REQUIREMENTS

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PACKAGING AND STORAGE: Preserve in tight, light-resistant containers at controlled room temperature_{▲(USP 1- May-2019)}

USP REFERENCE STANDARDS (11)

USP Nifedipine RS

USP Nifedipine Nitrophenylpyridine Analog RS

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

C₁₇H₁₆N₂O₆         344.33

USP Nifedipine Nitrosophenylpyridine Analog RS

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

C₁₇H₁₆N₂O₅         328.33