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Macrogols

GeneralNotices

(Ph.Eur.monograph1444)

Actionanduse

Nonionicsurfactant.

PhEur

DEFINITION

MixturesofpolymerswiththegeneralformulaH[OCH2CH2]nOHwherenrepresentstheaveragenumberofoxyethylenegroups.Thetypeofmacrogol

isdefinedbyanumberthatindicatestheaveragerelativemolecularmass.Asuitablestabilisermaybeadded.

CHARACTERS

IDENTIFICATION
A.Viscosity(seeTests).
B.To1ginatesttubeadd0.5mLofsulfuricacidR,closethetesttubewithastopperfittedwithabentdeliverytubeandheatuntilwhitefumesare
evolved.Collectthefumesviathedeliverytubeinto1mLofmercuricchloridesolutionR.Anabundant,white,crystallineprecipitateisformed.
C.To0.1gadd0.1gofpotassiumthiocyanateRand0.1gofcobaltnitrateRandmixthoroughlywithaglassrod.Add5mLofmethylenechlorideR
andshake.Theliquidphasebecomesblue.

TESTS

Appearanceofsolution

Thesolutionisclear(2.2.1)andnotmoreintenselycolouredthanreferencesolutionBY6(2.2.2,MethodII).

Dissolve12.5ginwaterRanddiluteto50mLwiththesamesolvent.

Acidityoralkalinity

Dissolve5.0gin50mLofcarbondioxidefreewaterRandadd0.15mLofbromothymolbluesolutionR1.Thesolutionisyelloworgreen.Notmore
than0.1mLof0.1Msodiumhydroxideisrequiredtochangethecolouroftheindicatortoblue.

Viscosity(2.2.9)

TheviscosityiscalculatedusingadensitygiveninTable1444.1.

Formacrogolswitharelativemolecularmassgreaterthan400,determinetheviscosityona50percentm/msolutionofthesubstancetobeexamined.

Freezingpoint(2.2.18)

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SeeTable1444.2.

Hydroxylvalue

Introducemg(seeTable1444.3)intoadryconicalflaskfittedwitharefluxcondenser.Add25.0mLofphthalicanhydridesolutionR,swirltodissolve
andboilunderarefluxcondenseronahotplatefor60min.Allowtocool.Rinsethecondenserfirstwith25mLofpyridineRandthenwith25mLof
waterR,add1.5mLofphenolphthaleinsolutionRandtitratewith1Msodiumhydroxideuntilafaintpinkcolourisobtained(n1mL).Carryoutablank

test(n2mL).Calculatethehydroxylvalueusingthefollowingexpression:

Formacrogolswitharelativemolecularmassgreaterthan1000,ifthewatercontentismorethan0.5percent,dryasampleofsuitablemassat100
105Cfor2handcarryoutthedeterminationofthehydroxylvalueonthedriedsample.

Reducingsubstances

Dissolve1gin1mLofa10g/LsolutionofresorcinolRandwarmgentlyifnecessary.Add2mLofhydrochloricacidR.After5minthesolutionisnot
moreintenselycolouredthanreferencesolutionR3(2.2.2,MethodI).

Formaldehyde

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Maximum30ppm.

Testsolution To1.00gadd0.25mLofchromotropicacid,sodiumsaltsolutionR,coolinicedwaterandadd5.0mLofsulfuricacidR.Allowtostand
for15minanddiluteslowlyto10mLwithwaterR.

Referencesolution Dilute0.860gofformaldehydesolutionRto100mLwithwaterR.Dilute1.0mLofthissolutionto100mLwithwaterR.Ina10mL
flask,mix1.00mLofthissolutionand0.25mLofchromotropicacid,sodiumsaltsolutionR,coolinicedwaterandadd5.0mLofsulfuricacidR.Allow
tostandfor15minanddiluteslowlyto10mLwithwaterR.

Blanksolution Ina10mLflaskmix1.00mLofwaterRand0.25mLofchromotropicacid,sodiumsaltsolutionR,coolinicedwaterandadd5.0mLof
sulfuricacidR.Diluteslowlyto10mLwithwaterR.

Determinetheabsorbance(2.2.25)ofthetestsolutionat567nm,againsttheblanksolution.Itisnothigherthanthatofthereferencesolution.

Iftheuseofmacrogolswithahighercontentofformaldehydemayhaveadverseeffects,thecompetentauthoritymayimposealimitofnotmorethan
15ppm.

Ethyleneglycolanddiethyleneglycol

carryoutthistestonlyifthemacrogolhasarelativemolecularmassbelow1000.

Gaschromatography(2.2.28).

Testsolution Dissolve5.00gofthesubstancetobeexaminedinacetoneRanddiluteto100.0mLwiththesamesolvent.

Referencesolution Dissolve0.10gofethyleneglycolRand0.50gofdiethyleneglycolRinacetoneRanddiluteto100.0mLwiththesamesolvent.
Dilute1.0mLofthesolutionto10.0mLwithacetoneR.

Column:
material:glass

size:l=1.8m,=2mm

stationaryphase:silaniseddiatomaceousearthforgaschromatographyR,impregnatedwith5percentm/mofmacrogol20000R.

Carriergas nitrogenforchromatographyR.

Flowrate 30mL/min.

Temperature:
column:ifnecessary,preconditionthecolumnbyheatingat200Cforabout15hadjusttheinitialtemperatureofthecolumntoobtaina
retentiontimeof1416minfordiethyleneglycolraisethetemperatureofthecolumnbyabout30Catarateof2C/minbutwithoutexceeding
170C

injectionportanddetector:250C.

Detection Flameionisation.

Injection 2L.

Carryout5replicateinjectionstochecktherepeatabilityoftheresponse.

Limit Maximum0.4percent,calculatedasthesumofthecontentsofethyleneglycolanddiethyleneglycol.

Ethyleneoxideanddioxan(2.4.25)

Maximum1ppmofethyleneoxideand10ppmofdioxan.

Water(2.5.12)

Maximum2.0percentformacrogolswitharelativemolecularmassnotgreaterthan1000andmaximum1.0percentformacrogolswitharelative
molecularmassgreaterthan1000,determinedon2.00g.

Sulfatedash(2.4.14)

Maximum0.2percent,determinedon1.0g.

STORAGE

Inanairtightcontainer.

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LABELLING
Thelabelstates:
thetypeofmacrogol

thecontentofformaldehyde.

FUNCTIONALITYRELATEDCHARACTERISTICS

Thissectionprovidesinformationoncharacteristicsthatarerecognisedasbeingrelevantcontrolparametersforoneormorefunctionsofthe
substancewhenusedasanexcipient(seechapter5.15).SomeofthecharacteristicsdescribedintheFunctionalityrelatedcharacteristicssectionmay
alsobepresentinthemandatorypartofthemonographsincetheyalsorepresentmandatoryqualitycriteria.Insuchcases,acrossreferencetothe
testsdescribedinthemandatorypartisincludedintheFunctionalityrelatedcharacteristicssection.Controlofthecharacteristicscancontributetothe
qualityofamedicinalproductbyimprovingtheconsistencyofthemanufacturingprocessandtheperformanceofthemedicinalproductduringuse.
Wherecontrolmethodsarecited,theyarerecognisedasbeingsuitableforthepurpose,butothermethodscanalsobeused.Whereverresultsfora
particularcharacteristicarereported,thecontrolmethodmustbeindicated.

Thefollowingcharacteristicmayberelevantformacrogolsusedassolvent.

Viscosity

(seeTests).

Thefollowingcharacteristicsmayberelevantformacrogolsusedassuspensionstabiliserandthickener.

Viscosity

(seeTests).

Thefollowingcharacteristicmayberelevantformacrogolsusedaslubricantintablets.

Particlesizedistribution(2.9.31)

Thefollowingcharacteristicsmayberelevantformacrogolsusedassuppositorybaseandformacrogolsusedinhydrophilicointments.

Viscosity

(seeTests).

Meltingpoint(2.2.15)

PhEur

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