Nifedipine Delayed-release Fine Granules
Nifedipine Delayed-release Fine Granules contain not less than 95.0% and not more than 105.0% of the labeled amount of nifedipine (C17H18N2O6: 346.33).
Method of preparation
Prepare as directed under Granules, with Nifedipine.
Identification
Conduct this procedure without exposure to light, using light-resistant vessels. Shake for 15 minutes a quantity of powdered Nifedipine Delayed-release Fine Granules, equivalent to 3 mg of Nifedipine, with 100 mL of methanol, and filter. Determine the absorption spectrum of the filtrate so obtained as directed under Ultraviolet-visible Spectrophotometry <2.24>: it exhibits a broad absorption maximum between 335 nm and 356 nm.
Uniformity of dosage units <6.02>
Perform the test according to the following method: the Granules in single-dose packages meet the requirement of the Content uniformity test.
Conduct this procedure without exposure to light, using light-resistant vessels. To the total content of 1 package of Nifedipine Delayed-release Fine Granules add 50mL of a mixture of methanol and water (9:1), agitate for 15 minutes with the aid of ultrasonic waves with occasional shaking, and shake for further 15 minutes. Then, add methanol to make exactly V mL so that each mL contains about 0.1 mg of nifedipine (C17H18N2O6). Filter this solution through a membrane filter with a pore size not exceeding 0.45 µm. Discard the first 10 mL of the filtrate, pipet 5 mL of the subsequent filtrate, add methanol to make exactly 10 mL, and use this solution as the sample solution.
Separately, weigh accurately about 50 mg of nifedipine for assay, previously dried at 105oC for 2 hours, and dissolve in methanol to make exactly 50 mL. Pipet 5mL of this solution, add methanol to make exactly 100 mL, and use this solution as the standard solution. Then, proceed as directed in the Assay.
Amount (mg) of nifedipine (C17H18N2O6)
＝ MS × AT/AS × V/500
MS: Amount (mg) of nifedipine for assay taken
Dissolution <6.10>
When the tests are performed at 50 revolutions per minute according to the Paddle method, using 900 mL each of 1st and 2nd fluids for dissolution test as the dissolution medium, the dissolution rate in the test using the 1st fluid for dissolution test in 60 minutes is not more than 15%, and that in the test using the 2nd fluid for dissolution test in 30 minutes is not less than 75%.
Conduct this procedure without exposure to light, using light-resistant vessels. Start the test with an accurately weighed amount of Nifedipine Delayed-release Fine Granules, equivalent to about 20 mg of nifedipine (C17H18N2O6), withdraw not less than 20 mL of the medium at the specified minute after starting the test, and filter through a membrane filter with a pore size not exceeding 0.45 µm. Discard the first 10 mL of the filtrate, pipet 5 mL of the subsequent filtrate, add the dissolution medium to make exactly 10 mL, and use this solution as the sample solution.
Separately, weigh accurately about 28 mg of nifedipine for assay, previously dried at 105oC for 2 hours, dissolve in 50 mL of methanol, and add the dissolution medium to make exactly 100 mL. Pipet 2 mL of this solution, add the dissolution medium to make exactly 50 mL, and use this solution as the standard solution. Perform the test with exactly 50 µL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01>, and determine the peak areas, AT and AS, of nifedipine in each solution.
Dissolution rate (%) with respect to the labeled amount of nifedipine (C17H18N2O6)
＝ MS/MT × AT/AS × 1/C × 72
MS: Amount (mg) of nifedipine for assay taken
MT: Amount (g) of Nifedipine Delayed-release Fine Granules taken
C: Labeled amount (mg) of nifedipine (C17H18N2O6) in 1 g
Operating conditions—
Proceed as directed in the operating conditions in the Assay.
System suitability—
System performance: When the procedure is run with 50 µL of the standard solution under the above operating conditions, the number of theoretical plates and the symmetry factor of the peak of nifedipine are not less than 4000 and not more than 1.5, respectively.
System repeatability: When the test is repeated 6 times with 50 µL of the standard solution under the above operating conditions, the relative standard deviation of the peak area of nifedipine is not more than 1.0%.
Assay
Conduct this procedure without exposure to light, using light-resistant vessels. Weigh accurately a portion of powdered Nifedipine Delayed-release Fine Granules, equivalent to about 10 mg of nifedipine (C17H18N2O6), add 50 mL of a mixture of methanol and water (9:1), shake vigorously for 15 minutes, and add methanol to make exactly 100 mL.
Filter this solution through a membrane filter with a pore size not exceeding 0.45 µm. Discard the first 10 mL of the filtrate, pipet 5 mL of the subsequent filtrate, add methanol to make exactly 10 mL, and use this solution as the sample solution. Separately, weigh accurately about 50 mg of nifedipine for assay, previously dried at 105oC for 2 hours, and dissolve in methanol to make exactly 50 mL. Pipet 5 mL of this solution, add methanol to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 10 µL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of nifedipine in each solution.
Amount (mg) of nifedipine (C17H18N2O6)
＝ MS × AT/AS × 1/5
MS: Amount (mg) of nifedipine for assay taken
Operating conditions—
Detector: An ultraviolet absorption photometer (wavelength: 230 nm).
Column: A stainless steel column 4.6 mm in inside diameter and 15 cm in length packed with octadecylsilanized silicagel for liquid chromatography (5 µm in particle diameter).
Column temperature: A constant temperature of about 40oC.
Mobile phase: Adjust to pH 6.1 of a mixture of methanol and diluted 0.05 mol/L disodium hydrogen phosphate TS (1 in 5) (11:9) with phosphoric acid.
Flow rate: Adjust so that the retention time of nifedipine is about 6 minutes.
System suitability—
System performance: When the procedure is run with 10 µL of the standard solution under the above operating conditions, the number of theoretical plates and the symmetry factor of the peak of nifedipine are not less than 4000 and not more than 1.2, respectively.
System repeatability: When the test is repeated 6 times with 10 µL of the standard solution under the above operating conditions, the relative standard deviation of the peak area of nifedipine is not more than 1.0%.
Containers and storage
Containers—Tight containers.
Storage—Light-resistant.
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