Isosorbide Dinitrate Extended-Release Capsules
»Isosorbide Dinitrate Extended-Release Capsules contain not less than 90.0percent and not more than 110.0percent of the labeled amount of C6H8N2O8.
Packaging and storage—
Preserve in well-closed containers.
Identification—
The finely powdered contents of the Capsules respond to the Identificationtest under Isosorbide Dinitrate Tablets.If separation of interferences is required,transfer a quantity of the finely powdered contents of the Capsules,equivalent to about 20mg of isosorbide dinitrate,to a glass-stoppered centrifuge tube,add 10mLof sodium hydroxide solution (1in 250),shake to wet the powder,add 15mLof 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 30minutes,filter the solution while still in the freezer.Evaporate the solvent,and dry the residue in vacuum over calcium chloride for 16hours:the IRabsorption spectrum of the residue so obtained,dissolved in 0.4mLof 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 1650cm-1,1284cm-1and 1275cm-1(a doublet),1106cm-1,and 844cm-1.
,the beaker and a short-stem funnel fitted with a cotton plug that previously has been chloroform-washed and dried.After 30minutes,filter the solution while still in the freezer.Evaporate the solvent,and dry the residue in vacuum over calcium chloride for 16hours:the IRabsorption spectrum of the residue so obtained,dissolved in 0.4mLof 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 1650cm-1,1284cm-1and 1275cm-1(a doublet),1106cm-1,and 844cm-1.
Drug release á724ñ—
Proceed as directed for Method Bunder Delayed-release Articles—General Drug Release Standard,except to operate the apparatus in the acid medium for 1hour instead of 2hours and to use Acceptance Table 1under Extended-release Articles—General Drug Release Standard.
Apparatus 2:
50rpm.
Times:
2hours,4hours,and 8hours.
Determine the amount of C6H8N2O8dissolved using the following method.
Mobile phase—
Prepare a filtered and degassed mixture of 0.05Mmonobasic potassium phosphate and acetonitrile (52:48).Make adjustments,if necessary (see System Suitabilityunder Chromatography á621ñ).
Chromatographic system
(see Chromatography á621ñ)—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 2mLper minute.Chromatograph a Standard solution of USP Diluted Isosorbide Dinitrate RSin the same medium,and record the chromatograms as directed under 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 20µL)of a filtered portion of the solution under test,and record the chromatograms.Determine the amount of C6H8N2O8dissolved in comparison with a Standard solution of USP Diluted Isosorbide Dinitrate RSin the same medium and similarly chromatographed.
Tolerances—
The percentages of the labeled amount of C6H8N2O8dissolved at the times specified conform to Acceptance Table 1.[NOTE—The test times given are cumulative beginning with the 1hour in the acid medium.]
| Time (hours) | Amount dissolved |
| 2 | between 10%and 30% |
| 4 | between 40%and 75% |
| 8 | not less than 75% |
Uniformity of dosage units á905ñ:
meet the requirements.
Assay—
Buffer solution
,Mobile phase,Internal standard solution,Standard preparation,and Chromatographic system—Prepare as directed in the Assayunder Diluted Isosorbide Dinitrate.
Assay preparation—
Weigh and finely powder the contents of not fewer than 20Capsules.Transfer an accurately weighed portion of the powder,equivalent to about 12.5mg of isosorbide dinitrate,to a dry,50-mLvolumetric flask,add about 30mLof 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 15mLof a 1in 10dilution of Buffer solution in water by heating on a steam bath for 1hour with frequent shaking,then add 15mLof methanol.]Shake for 30minutes.Add 8.0mLof Internal standard solution,cool to room temperature,add 8mLof a 1in 10dilution of Buffer solutionin water,dilute with Mobile phaseto volume,and mix.Filter a portion through a microporous membrane filter.
Procedure—
Proceed as directed for Procedurein the Assayunder Diluted Isosorbide Dinitrate.Calculate the quantity,in mg,of C6H8N2O8in the portion of Capsules taken by the formula:
50C(RU/RS),
in which Cis the concentration,in mg per mL,of isosorbide dinitrate from the USP Isosorbide Dinitrate RStaken for the Standard preparation,and RUand RSare the ratios of the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 1086
Phone Number:1-301-816-8305