Isosorbide Dinitrate Extended-Release Capsules
» Isosorbide Dinitrate Extended-Release Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of C6H8N2O8.
Packaging and storage Preserve in well-closed containers.
USP Reference standards 11
Identification The finely powdered contents of the Capsules respond to the Identification test under Isosorbide Dinitrate Tablets. If separation of interferences is required, transfer a quantity of the finely powdered contents of the Capsules, equivalent to about 20 mg of isosorbide dinitrate, to a glass-stoppered centrifuge tube, add 10 mL of sodium hydroxide solution (1 in 250), shake to wet the powder, add 15 mL of solvent hexane, and shake again. Centrifuge the mixture, and transfer the upper phase to a beaker. Place in a freezer, at a temperature of about 14, the beaker and a short-stem funnel fitted with a cotton plug that previously has been chloroform-washed and dried. After 30 minutes, filter the solution while still in the freezer. Evaporate the solvent, and dry the residue in vacuum over calcium chloride for 16 hours: the IR absorption spectrum of the residue so obtained, dissolved in 0.4 mL of chloroform and determined with the use of matched 0.1-mm cells, shows all of the significant absorption bands present in the spectrum obtained for a similar preparation from the residue obtained from USP Diluted Isosorbide Dinitrate RS. The major peaks are at about 1650 cm1, 1284 cm1 and 1275 cm1 (a doublet), 1106 cm1, and 844 cm1.
Dissolution 711 Proceed as directed for Method B in Delayed-Release Dosage Forms in Procedure, Apparatus 1 and Apparatus 2, except to operate the apparatus in the acid medium for 1 hour instead of 2 hours and to use Acceptance Table 2 in Extended-Release Dosage Forms in Interpretation.
Apparatus 2: 50 rpm.
Times: 2, 4, and 8 hours.
Determine the amount of C6H8N2O8 dissolved employing the following method.
Mobile phase Prepare a filtered and degassed mixture of 0.05 M monobasic potassium phosphate and acetonitrile (52:48). Make adjustments, if necessary (see System Suitability under Chromatography 621).
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 224-nm detector and a 4-mm × 30-cm column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph a Standard solution of USP Diluted Isosorbide Dinitrate RS in the same medium, and record the chromatograms as directed for Procedure: the tailing factor is not more than 2.5; and the relative standard deviation is not more than 2.0%.
Procedure Separately inject equal volumes (about 20 µL) of a filtered portion of the solution under test, and record the chromatograms. Determine the amount of C6H8N2O8 dissolved in comparison with a Standard solution of USP Diluted Isosorbide Dinitrate RS in the same medium and similarly chromatographed.
Tolerances The percentages of the labeled amount of C6H8N2O8 dissolved at the times specified conform to Acceptance Table 2. [noteThe test times given are cumulative, beginning with the 1 hour in the acid medium. ]
Uniformity of dosage units 905: meet the requirements.
Buffer solution , Mobile phase, Internal standard solution, Standard preparation, and Chromatographic systemPrepare as directed in the Assay under Diluted Isosorbide Dinitrate.
Assay preparation Weigh and finely powder the contents of not fewer than 20 Capsules. Transfer an accurately weighed portion of the powder, equivalent to about 12.5 mg of isosorbide dinitrate, to a dry, 50-mL volumetric flask, add about 30 mL of Mobile phase, and shake the mixture by hand immediately, to prevent clumping. If clumping persists, disperse with the aid of sonication, or break the aggregates with a stirring rod, or warm on a steam bath while keeping the flask stoppered, or allow the flask to stand until the clumps dissipate. [noteIf clumping still continues, discard the mixture, and instead disperse an accurately weighed test portion in 15 mL of a 1 in 10 dilution of Buffer solution in water by heating on a steam bath for 1 hour with frequent shaking, then add 15 mL of methanol. ] Shake for 30 minutes. Add 8.0 mL of Internal standard solution, cool to room temperature, add 8 mL of a 1 in 10 dilution of Buffer solution in water, dilute with Mobile phase to volume, and mix. Pass a portion through a microporous membrane filter.
Procedure Proceed as directed for Procedure in the Assay under Diluted Isosorbide Dinitrate. Calculate the quantity, in mg, of C6H8N2O8 in the portion of Capsules taken by the formula:
50C(RU / RS)in which C is the concentration, in mg per mL, of isosorbide dinitrate from the USP Diluted Isosorbide Dinitrate RS taken for the Standard preparation; and RU and RS are the ratios of the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 3588Pharmacopeial Forum: Volume No. 31(1) Page 160