Packaging and storage—
Preserve in well-closed containers.
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 cm
1, 1284 cm
1 and 1275 cm
1 (a doublet), 1106 cm
1, and 844 cm
1.
Drug release 
724
—
Proceed as directed for
Method B under
Delayed-Release Articles—General Drug Release Standard, except to operate the apparatus in the acid medium for 1 hour instead of 2 hours and to use
Acceptance Table 1 under
Extended-Release Articles—General Drug Release Standard.
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 C
6H
8N
2O
8 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 C
6H
8N
2O
8 dissolved at the times specified conform to
Acceptance Table 1. [NOTE—The test times given are cumulative beginning with the 1 hour in the acid medium.
]
| Time (hours) |
 Amount dissolved |
| 2 |
between 10% and 30% |
| 4 |
between 40% and 75% |
| 8 |
not less than 75% |
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 C
6H
8N
2O
8 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 C
6H
8N
2O
8 dissolved at the times specified conform to
Acceptance Table 2. [NOTE—The test times given are cumulative, beginning with the 1 hour in the acid medium.
]
| Time (hours) |
Amount dissolved |
| 2 |
between 10% and 30% |
| 4 |
between 40% and 75% |
| 8 |
not less than 75% |
(Official April 1, 2006)
Assay—
Buffer solution
,
Mobile phase,
Internal standard solution,
Standard preparation, and
Chromatographic system—Prepare 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. [NOTE—If 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 C
6H
8N
2O
8 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 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.
