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Levothyroxine Sodium Tablets
Levothyroxine Sodium Tablets
Levothyroxine Sodium Tablets
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LevothyroxineSodiumTablets
LevothyroxineSodiumTabletscontainnotlessthan90.0percentandnot
morethan110.0percentofthelabeledamountoflevothyroxinesodium
(C15H10I4NNaO4).
Packaging and storagePreserveintight,light-resistantcontainers.
LabelingWhenmorethanone Dissolution testisgiven,thelabelingstatesthe Dissolution test
usedonlyif Test 1 isnotused.
USP Reference standards
USP Levothyroxine RS.
USP Liothyronine RS.
11
Identification
Solvent systemMix5volumesoftert-amylalcohol,4volumesofwater,and1volumeof
ammoniumhydroxide,shake,andallowtostand.Transfertheupperphasetoasuitable
chromatographicchamberarrangedforthin-layerchromatography,pouringitoverthepaper
lining,coverthechamber,andallowtostandfor1hour.
Detection reagentAdd65mLof2Nhydrochloricacidto50mLofa1in10solutionofsodium
arsenitein1Nsodiumhydroxide,withvigorousstirring.Mix1volumeofthissolutionwith5
volumesofa27in1000solutionofferricchloridein2Nhydrochloricacidand5volumesof
freshlypreparedpotassiumferricyanidesolution(35in1000).
Standard solutionPrepareasolutionofabout15mgofUSP Levothyroxine RS,accurately
weighed,in100mLofamixtureof19volumesofmethanoland1volumeofammonium
hydroxide.Dilute10.0mLofthissolutionwiththesamesolventto50.0mL,andmix.
Test solutionShakeanamountofpowderedTablets,equivalenttoabout60goflevothyroxine
sodium,with2mLofamixtureof19volumesofmethanoland1volumeofammoniumhydroxide
inacentrifugetubefor10minutes,andcentrifuge.
ProcedureApply10-Lvolumesofthe Test solution andofthe Standard solution,respectively,
toathin-layerchromatographicplatecoatedwitha0.1-mmlayerofcellulose.Developtheplatein
the Solvent system untilthesolventfronthasmovednotlessthan10cmbeyondthepointof
applicationofthe Test solution,air-dry,andspraytheplatewith Detection reagent: the
chromatogramofthe Test solution showsabluespotcorrespondingin R valuetothe
chromatogramfromthelevothyroxine Standard solution.
F
Dissolution
711 [NOTEAllcontainersthatareincontactwithsolutionscontaining
levothyroxinesodiumaretobemadeofglass.]
TEST1
Medium: 0.01Nhydrochloricacidcontaining0.2%sodiumlaurylsulfate;500mL.
Apparatus 2: 50rpm.
Time: 45minutes.
DeterminetheamountofC 15H10I4NNaO4dissolvedbyemployingthefollowingmethod.
Mobile phasePrepareafilteredanddegassedmixtureofmethanoland0.1%phosphoricacid
(60:40).Makeadjustmentsifnecessary(seeSystem Suitability underChromatography
621 ).
Test 2.
Medium, Apparatus, Mobile phase, Standard solution, Test solution, Chromatographic system,
andProcedureProceedasdirectedfor Test 1.
Time: 15minutes.
TolerancesNotlessthan80% (Q) ofthelabeledamountofC 15H10I4NNaO4isdissolvedin15
minutes.
TEST3Iftheproductcomplieswiththistest,thelabelingindicatesthatitmeetsUSP Dissolution
Test 3.
Medium, Apparatus, Time, Standard solution, andTest solutionProceedasdirectedforTest 1.
621 ).
Test 4.
NOTEDonotusepaddlestirrerswithsyntheticcoating.
Medium: 0.01Nhydrochloricacid;500mLfortabletslabeledtocontainbetween25gand175
goflevothyroxinesodium;900mLfortabletslabeledtocontain200gor300gof
levothyroxinesodium.
Apparatus 2: 75rpm.
Time: 45minutes.
DeterminetheamountofC 15H10I4NNaO4dissolvedbyemployingthefollowingmethod.
Mobile phasePrepareafilteredanddegassedmixtureofwater,acetonitrile,and85%
orthophosphoricacid(700:500:2).Makeadjustmentsifnecessary(see System Suitabilityunder
Chromatography
621 ).
Test solutionUseacentrifugedportionofthesolutionundertest.
Chromatographic system (see Chromatography 621 )Theliquidchromatographisequipped
witha225-nmdetectoranda4.0-mm12.5-cmcolumnthatcontainspackingL7.Theflowrateis
about1.5mLperminute.Chromatographthe Standard solution, andrecordthepeakresponses
asdirectedforProcedure:thetailingfactorisnotmorethan1.5;andtherelativestandard
deviationisnotmorethan4.0%.
ProcedureSeparatelyinjectequalvolumes(about500L)ofthe Standard solutionandthe
Test solution intothechromatograph,recordthechromatograms,andmeasuretheresponsesfor
themajorpeaks.CalculatetheamountofC 15H10I4NNaO4.
TolerancesNotlessthan80%(Q) ofthelabeledamountofC 15H10I4NNaO4isdissolvedin45
minutes.
Uniformity of dosage units
905 : meettherequirements.
inwhich672.96and650.98arethemolecularweightsofliothyroninesodiumandliothyronine,
respectively; Cistheconcentration,ingpermL,ofUSP Liothyronine RSinthe Standard
solution; Wistheamount,ing,oflevothyroxinesodiumintheportionofTablets,basedonthe
labelclaim,takentopreparetheTest solution;and r and r aretheliothyroninepeakresponses
obtainedfromthe Test solution andthe Standard solution, respectively:notmorethan2.0%of
liothyronineisfound.
U
Assay
Mobile phase, Standard preparation,andChromatographic systemProceedasdirectedinthe
Assay under Levothyroxine Sodium.
Assay preparationWeighandfinelypowdernotfewerthan20Tablets.Transferanaccurately
weighedportionofthepowder,equivalenttoabout100goflevothyroxinesodium,toacentrifuge
tube,add2glassbeads,pipet10mLof Mobile phase intothetube,andmixonavortexmixerfor
3minutes.Centrifugetoobtainaclearsupernatant,filteringifnecessary.
inwhich798.85and776.87arethemolecularweightsoflevothyroxinesodiumandlevothyroxine,
respectively; C istheconcentration,ingpermL,ofUSP Levothyroxine RSinthe Standard
preparation; and r and r arethelevothyroxinepeakresponsesobtainedfromthe Assay
preparation andthe Standard preparation, respectively.
U