Sei sulla pagina 1di 3

11/10/2016

GeneralChapters:<1150>PHARMACEUTICALSTABILITY

GeneralChapters:<1150>PHARMACEUTICALSTABILITY SearchUSP29 Go Global Pharma Exporter Global Full line

SearchUSP29

Go
Go
Exporter. Orphans, Unlicensed, Specials, Onco gnhindia.com 1150 PHARMACEUTICALSTABILITY
Exporter. Orphans, Unlicensed, Specials, Onco gnhindia.com 1150 PHARMACEUTICALSTABILITY
Exporter. Orphans, Unlicensed, Specials, Onco gnhindia.com 1150 PHARMACEUTICALSTABILITY

1150 PHARMACEUTICALSTABILITY

Specials, Onco gnhindia.com 1150 PHARMACEUTICALSTABILITY

Theterm“stability,”withrespecttoadrugdosageform,referstothechemicalandphysicalintegrityofthedosageunitand,

whenappropriate,theabilityofthedosageunittomaintainprotectionagainstmicrobiologicalcontamination.Theshelflife

ofthedosageformisthetimelapsefrominitialpreparationtothespecifiedexpirationdate.Themonographspecifications

ofidentity,strength,quality,andpurityapplythroughouttheshelflifeoftheproduct.

Thestabilityparametersofadrugdosageformcanbeinfluencedbyenvironmentalconditionsofstorage(temperature,

light,air,andhumidity),aswellasthepackagecomponents.Pharmacopeialarticlesshouldincluderequiredstorage

conditionsontheirlabeling.Thesearetheconditionsunderwhichtheexpirationdateshallapply.Thestoragerequirements

specifiedinthelabelingforthearticlemustbeobservedthroughoutthedistributionofthearticle(i.e.,beyondthetimeit

leavesthemanufactureruptoandincludingitshandlingbythedispenserorsellerofthearticletotheconsumer).Although

labelingfortheconsumershouldindicateproperstorageconditions,itisrecognizedthatcontrolbeyondthedispenseror

sellerisdifficult.Thebeyond­usedateshallbeplacedonthecontainerlabel.

StabilityProtocols

Stabilityofmanufactureddosageformsmustbedemonstratedbythemanufacturer,usingmethodsadequateforthe

purpose.Monographassaysmaybeusedforstabilitytestingiftheyarestability­indicating(i.e.,iftheyaccurately

differentiatebetweentheintactdrugmoleculesandtheirdegradationproducts).Stabilityconsiderationsshouldincludenot

onlythespecificcompendialrequirements,butalsochangesinphysicalappearanceoftheproductthatwouldwarnusers

thattheproduct'scontinuedintegrityisquestionable.

Stabilitystudiesonactivesubstancesandpackageddosageformsareconductedbymeansof“real­time,”long­termtests

atspecifictemperaturesandrelativehumiditiesrepresentingstorageconditionsexperiencedinthedistributionchainofthe

climaticzone(s)ofthecountryorregionoftheworldconcerned.Labelingofthepackagedactivesubstanceordosageform

shouldreflecttheeffectsoftemperature,relativehumidity,air,andlightonitsstability.Labeltemperaturestoragewarnings

willbothreflecttheresultsofthereal­timestoragetestsandallowforexpectedseasonalexcursionsoftemperature.

ControlledRoomTemperature

Controlledroomtemperature(seeStorageTemperatureandHumidityinPreservation,Packaging,Storage,andLabeling

underGeneralNoticesandRequirements)delineatestheallowabletoleranceinstoragecircumstancesatanylocationinthe

chainofdistribution(e.g.,pharmacies,hospitals,andwarehouses).Thisterminologyalsoallowspatientsorconsumersto

becounseledastoappropriatestoragefortheproduct.Productsmaybelabeledeithertostoreat“Controlledroom

temperature”ortostoreattemperatures“upto25

temperature”ortostoreattemperatures“upto25 ”wherelabelingissupportedbylong­termstabilitystudiesatthe

11/10/2016

GeneralChapters:<1150>PHARMACEUTICALSTABILITY

GeneralChapters:<1150>PHARMACEUTICALSTABILITY designatedstorageconditionof25 . Controlledroomtemperature
GeneralChapters:<1150>PHARMACEUTICALSTABILITY designatedstorageconditionof25 . Controlledroomtemperature

designatedstorageconditionof25 .Controlledroomtemperaturelimitsthepermissibleexcursionstothoseconsistentwith

Kelvin(K)

Kelvin(K) Fahrenheit(F) Celsius(C)

Fahrenheit(F) Celsius(C)

themaintenanceofameankinetictemperaturecalculatedtobenotmorethan25 .SeeMeanKineticTemperature.The

commoninternationalguidelineforlong­termstabilitystudiesspecifies25±2 at60±5%relativehumidity.Accelerated

at60±5%relativehumidity.Accelerated studiesarespecifiedat40±2

studiesarespecifiedat40±2 andat75±5%relativehumidity.Acceleratedstudiesalsoallowtheinterpretationofdata andinformationonshort­termspikesinstorageconditionsinadditiontotheexcursionsallowedbycontrolledroom temperature.

Theterm“roomtemperature”isusedindifferentwaysindifferentcountries,andforproductstobeshippedoutsidethe

continentalU.S.itisusuallypreferableforproductlabelingtorefertoamaximumstoragetemperatureortemperaturerange

indegreesCelsius.

MeanKineticTemperature

MeanKineticTemperature(MKT)isdefinedasthesinglecalculatedtemperatureatwhichthetotalamountofdegradation overaparticularperiodisequaltothesumoftheindividualdegradationsthatwouldoccuratvarioustemperatures.Thus, MKTmaybeconsideredasanisothermalstoragetemperaturethatsimulatesthenonisothermaleffectsofstorage temperaturevariation.Itisnotasimplearithmeticmean.MKTiscalculatedfromtemperaturesinastoragefacility.The temperaturesforcalculatingMKTcanbeconvenientlycollectedusingelectronicdevicesthatmeasuretemperaturesat

frequentintervals(e.g.,every15minutes).MKTcanbecalculateddirectlyorthedatacanbedownloadedtoacomputerfor

processing.Fordispensingsites,suchaspharmaciesandhospitals,wheretheuseofsuchinstrumentsmaynotbe

feasible,devicessuchashigh­lowthermometerscapableofindicatingweeklyhighandlowtemperaturesovera52­week

periodmaybeemployed.Thearithmeticmeanoftheweeklyhighandlowtemperaturesisthenusedinthecalculationof

MKT.MKTiscalculatedbythefollowingequation(derivedfromtheArrheniusequation):

inwhich T k isthemeankinetictemperature; D H
inwhich T k isthemeankinetictemperature; D H

inwhichT k isthemeankinetictemperature;DHistheheatofactivation,83.144kJ·mole 1 (unlessmoreaccurate

1 (unlessmoreaccurate informationisavailablefromexperimentalstudies); R
1 (unlessmoreaccurate informationisavailablefromexperimentalstudies); R
1 (unlessmoreaccurate informationisavailablefromexperimentalstudies); R

informationisavailablefromexperimentalstudies);Ristheuniversalgasconstant,8.3144×10 3 kJ·mole 1 ·degree 1 ; T 1 isthevalueforthetemperaturerecordedduringthefirsttimeperiod,e.g.,thefirstweek;T 2 isthevalueforthe

temperaturerecordedduringthesecondtimeperiod,e.g.,secondweek;andT n isthevalueforthetemperaturerecorded

duringthenthtimeperiod,e.g.,nthweek,nbeingthetotalnumberofstoragetemperaturesrecorded(minimumof52

weeklyentries)duringtheannualobservationperiod.[NOTE—Alltemperatures,T,areabsolutetemperaturesindegrees

Kelvin(K).]

ThefollowingisanexampleofatypicalstorageanddistributiontemperaturerangeinKelvindegreesandtheconversion

factorsusedtoconvertthisrangeintodegreesFahrenheitandCelsius.

Kelvin(K)

K e l v i n ( K ) Fahrenheit(F) Celsius(C) 59–86 ConversionFactors:
K e l v i n ( K ) Fahrenheit(F) Celsius(C) 59–86 ConversionFactors:

Fahrenheit(F) Celsius(C)

59–86

ConversionFactors:

FahrenheittoKelvin={[(F 32)×5/9]+273.1}

288.1–303.1

15–30

32)×5/9]+273.1} 288.1–303.1 15–30 CelsiustoKelvin=273.1+ C FahrenheittoCelsius=[(F 32)×5/9]

CelsiustoKelvin=273.1+ C

FahrenheittoCelsius=[(F 32)×5/9]

ClimaticZones

11/10/2016

GeneralChapters:<1150>PHARMACEUTICALSTABILITY

Forconvenienceinplanningforpackagingandstorage,andforstabilitystudies,internationalpracticeidentifiesfour

CalculatedData

DerivedData

climaticzones,whicharedescribedinTable1.TheUnitedStates,Europe,andJapanarecharacterizedbyzonesIandII.

%

%

ThevaluesinTable1arebasedonobservedtemperaturesandrelativehumidities,bothoutsideandinrooms,fromwhich

ClimaticZone

C

*

CMKT

**

RH

mbar ***

C RH

mbar

ClimaticZone C * CMKT ** RH mbar * * * C RH mbar
ClimaticZone C * CMKT ** RH mbar * * * C RH mbar
ClimaticZone C * CMKT ** RH mbar * * * C RH mbar

meankinetictemperaturesandaveragehumidityvaluesarecalculated. 1 Derivedvaluesarebasedoninspectionofdata fromindividualcitiesandonallowancesforamarginofsafetyinassignmentofthesespecifiedconditions.

Table1.InternationalClimaticZones

CalculatedData

DerivedData

 
      % %
 
      % %
 

%

%

 

ClimaticZone

C *

CMKT **

RH

mbar ***

C RH

C RH

mbar

I.Temperate

20.0

 

20.0

42

9.9

21

45

11.2

Japan 

 
 

UnitedKingdom

NorthernEurope

Canada 

 

Russia    UnitedKingdom NorthernEurope Canada     UnitedStates II. Mediterranean,Subtropical 21.6

 

UnitedStates

II.Mediterranean,Subtropical

21.6

 

22.0

52

13.5

25

60

19.0

 

UnitedStates

Japan

Japan

SouthernEurope

(Portugal­Greece)

III.Hot,Dry

26.4

 

27.9

35

11.9

30

35

15.0

 

Iran 

Iraq  27.9 35 11.9 30 35 15.0   Iran Sudan   IV. Hot,Humid 26.7   27.4

Sudan 

 

IV.Hot,Humid

26.7

 

27.4

76

26.6

30

70

30.0

Brazil26.7   27.4 76 26.6 30 70 30.0 Ghana Indonesia Nicaragua Philippines *

Ghana26.7   27.4 76 26.6 30 70 30.0 Brazil Indonesia Nicaragua Philippines * Datarecordedas<19

Indonesia  27.4 76 26.6 30 70 30.0 Brazil Ghana Nicaragua Philippines * Datarecordedas<19

Nicaragua76 26.6 30 70 30.0 Brazil Ghana Indonesia Philippines * Datarecordedas<19 calculatedas19. * *

Philippines26.6 30 70 30.0 Brazil Ghana Indonesia Nicaragua * Datarecordedas<19 calculatedas19. * *

70 30.0 Brazil Ghana Indonesia Nicaragua Philippines * Datarecordedas<19 calculatedas19. * *
70 30.0 Brazil Ghana Indonesia Nicaragua Philippines * Datarecordedas<19 calculatedas19. * *

* Datarecordedas<19 calculatedas19.

** Calculatedmeankinetictemperature.

*** Partialpressureofwatervapor.

Adiscussionofaspectsofdrugproductstabilitythatareofprimaryconcerntothepharmacistinthedispensingof

medicationsmaybefoundunder
medicationsmaybefoundunder

Inasmuchasthischapterisforpurposesofgeneralinformationonly,nostatementhereinisintendedtomodifyorsupplant

anyofthespecificrequirementspertinenttopharmaceuticalpreparations,whicharegivenelsewhereinthisPharmacopeia.

AuxiliaryInformation—StaffLiaison:DesmondG.Hunt,Ph.D.,SeniorScientificAssociate

ExpertCommittee:(PS05)PackagingandStorage05

USP29–NF24Page2994

PharmacopeialForum:VolumeNo.29(5)Page1625

PhoneNumber:1­301­816­8341