Nifedipine Capsules

» Nifedipine Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of nifedipine (C17H18N2O6).

Packaging and storage— Preserve in tight, light-resistant containers at a temperature between 15

and 25

USP Reference standards

—

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

[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. ]

Identification—

A: Visualizing solution—In a 100-mL volumetric flask dissolve 3 g of bismuth subnitrate and 30 g of potassium iodide with 10 mL of 3 N hydrochloric acid. Dilute with water to volume, and mix. Prior to use, transfer 10.0 mL of solution to a 100-mL volumetric flask, add 10 mL of 3 N hydrochloric acid, dilute with water to volume, and mix.

Standard solution— Prepare a Standard solution of USP Nifedipine RS in methylene chloride containing about 1.2 mg per mL.

Test solution— Using the technique described under Procedure for content uniformity in the test for Uniformity of dosage units, transfer the contents of 3 Capsules to a centrifuge tube, rinsing the scissors with about 20 mL of 0.1 N sodium hydroxide. Pipet 25 mL of methylene chloride into the tube, insert a stopper, invert several times, and carefully release the pressure in the tube. Insert the stopper again tightly, and shake gently for 1 hour. Centrifuge the tube for 10 minutes at 2000 to 2500 rpm. Remove the supernatant aqueous phase by aspiration with a syringe, and transfer 5.0 mL of the clarified lower layer to a suitable vial.

Procedure— Mix equal portions of the Standard solution and the Test solution. Apply separately 500 µL each of the Standard solution, the Test solution, and their mixture to a suitable thin-layer chromatographic plate (see Chromatography

621

) coated with a 0.5-mm layer of chromatographic silica gel mixture. Allow the spots to dry, and develop the chromatogram, protected from light, in a solvent system consisting of a mixture of ethyl acetate and cyclohexane (1:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and air-dry the plate until no odor is detectable. Immediately view the plate under short-wavelength UV light: each solution exhibits a dark blue major band at the same RF value of about 0.3. Spray the plate with Visualizing solution: each solution exhibits a compact light orange band on a yellow background.

B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.

Dissolution

711

—

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

Apparatus 2: 50 rpm.

Time: 20 minutes.

Standard solution— Dissolve an accurately weighed quantity of USP Nifedipine RS in an amount of methanol not exceeding 2% of the final volume, and dilute quantitatively and stepwise, if necessary, with Dissolution Medium to obtain a solution having a known appropriate concentration.

Procedure— Determine the amount of C17H18N2O6 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 340 nm on filtered portions of the solution under test, suitably diluted with Dissolution Medium, if necessary, in comparison with the Standard solution. [note—Filters must be checked for absorptive loss of nifedipine. ]

Tolerances— Not less than 80% (Q) of the labeled amount of C17H18N2O6 is dissolved in 20 minutes.

Uniformity of dosage units

905

: meet the requirements.

Procedure for content uniformity— With the point of a pair of sharp scissors, make a small hole at the end of 1 Capsule. Squeeze most of the contents into a 200-mL volumetric flask, cut the capsule in half, and drop it into the flask. Rinse the scissors with about 20 mL of methanol, quantitatively collecting the rinse in the flask. Dilute with methanol to volume, and mix to obtain the test solution. Dissolve an accurately weighed quantity of USP Nifedipine RS in methanol, and dilute quantitatively and stepwise with methanol to obtain a Standard solution having a known concentration of about 50 µg per mL. Concomitantly determine the absorbances of both solutions in 1-cm cells at the wavelength of maximum absorbance at about 350 nm, with a suitable spectrophotometer, using methanol as the blank. Calculate the quantity, in mg, of nifedipine (C17H18N2O6) in the Capsule by the formula:

(T / D)C(AU / AS)

in which T is the labeled quantity, in mg, of nifedipine in the Capsule; D is the concentration, in µg per mL, of nifedipine in the solution from the Capsule, on the basis of the labeled quantity per Capsule and the extent of dilution; C is the concentration, in µg per mL, of USP Nifedipine RS in the Standard solution; and AU and AS are the absorbances of the solution from the Capsule and the Standard solution, respectively.

Related compounds— [note—Protect the Standard nifedipine solution and the Test solution from actinic light. Conduct this test promptly after preparation of the Standard nifedipine solution and the Test solution. ]

Mobile phase— Prepare as directed in the Assay under Nifedipine.

Standard nifedipine solution— Prepare as directed for Standard nifedipine solution in the test for Related compounds under Nifedipine.

Reference solution 1— Prepare as directed for Reference solution 1 in the test for Related compounds under Nifedipine, except to make the final known concentration of about 6 µg per mL.

Reference solution 2— Prepare as directed for Reference solution 2 in the test for Related compounds under Nifedipine, except to make the final known concentration of about 1.5 µg per mL.

Standard solution— Transfer 5.0 mL of each of the two Reference solutions to a container, add 5.0 mL of Mobile phase, and mix.

Test solution— Prepare as directed for the Assay preparation in the Assay.

System suitability solution— Mix equal volumes of the Standard nifedipine solution and of each of the two Reference solutions.

Chromatographic system— Prepare as directed in the Assay. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between the nitrophenylpyridine analog and nitrosophenylpyridine analog peaks is not less than 1.5; the resolution, R, between the nitrosophenylpyridine analog and nifedipine peaks is not less than 1.0; and the relative standard deviation determined from the response for each analog in replicate injections is not more than 10%. The relative retention times are about 0.8 for the nitrophenylpyridine analog, about 0.9 for the nitrosophenylpyridine analog, and 1.0 for nifedipine.

Procedure— Separately inject equal volumes (about 25 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of each related compound in the portion of Capsules taken by the formula:

(V / 5)C(rU / rS)

in which V is the volume, in mL, of the Test solution, C is the concentration, in mg per mL, of the appropriate USP Nifedipine Analog RS in the Standard solution; and rU and rS are the peak responses of the corresponding related compound obtained from the Test solution and the Standard solution, respectively: not more than 2.0% of dimethyl 4-(2-nitrophenyl)-2,6-dimethylpyridine-3,5-dicarboxylate, corresponding to nifedipine nitrophenylpyridine analog, and not more than 0.5% of dimethyl 4-(2-nitrosophenyl)-2,6-dimethylpyridine-3,5-dicarboxylate, corresponding to nifedipine nitrosophenylpyridine analog, both relative to the nifedipine content, are found.

Assay— [note—Protect the Standard preparation and the Assay preparation from actinic light. Conduct the Assay promptly after preparation of the Standard preparation and the Assay preparation. ]

Mobile phase and Standard preparation— Prepare as directed in the Assay under Nifedipine.

Assay preparation— Transfer the contents of 5 Capsules with the aid of a small amount of methanol to a volumetric flask, quantitatively dilute with Mobile phase to obtain a total volume, V mL, of solution having a concentration of about 0.1 mg of nifedipine per mL. Pass through a solvent-resistant filter.

Chromatographic system (see Chromatography

621

)— The liquid chromatograph is equipped with a 265-nm detector, a 4.6-mm × 25-cm column that contains 5-µm packing L1, and a guard column that contains packing L1. The flow rate is about 1.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 4000 theoretical plates; the tailing factor is not more than 1.5; and the relative standard deviation for replicate injections is not more than 1.0%.

Procedure— Separately inject equal volumes (about 25 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of nifedipine (C17H18N2O6) in each Capsule taken by the formula:

(V / 5)C(rU / rS)

in which V is the volume, in mL, of the Assay preparation; C is the concentration, in mg per mL, of USP Nifedipine RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Sujatha Ramakrishna, Ph.D. Senior Scientific Liaison 1-301-816-8349	(SM22010) Monographs - Small Molecules 2
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org
711	Margareth R.C. Marques, Ph.D. Senior Scientific Liaison 1-301-816-8106	(GCDF2010) General Chapters - Dosage Forms

USP35–NF30 Page 4051

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