Basic tests for pharmaceutical dosage forms

140 Pages·1991·6.9 MB·English

by  World Health Organization

BASIC TESTS
FOR
PHARMACEUTICAL
DOSAGE FORMS
WORLD HEALTH ORGANIZATION, GENEVA
TheWorldHetlthOrguizatioiiteaspecialisedagencyoftheUnitedNations
with primary responsibility for international health matters and public health.
Through this organization, which was created in 1948, the health professions of
some 165 countries exchange their knowledge and experience with the aim of
makinfpossibletheattainmentbyaUdtiaettsoftheworldbytheyear2000ofa
levelofhealththatwillpemdtthemtoleadasociallyandeeonomicallyproductive
Ufe.
stimBuytatmienagnssucohfcdoiorpeectrattieochnniacamloncgooptehreamt,ioWnHwOithpriotsmoMteesmbtehre dSetavteelso,pmaenndtbcyt
comprehensive health services, the prevention and control of diseases, the
improvement ofenvironmentalconditions, the development ofhealth manpower,
theooofdinationanddevelopmentofbiomedindandhealthservicesreseardi,and
the planning and implementationofhealthpropammes.
Thesebroad fields ofendeavourencompassa widevarietyofactivities, suchas
developing systems of primary health care that reach the whole population of
Member countries^ promoting the health of mothers and childvenj combating
malnutrition: controlling malaria and other communicable diseases, including
tuberculosis and leprosy; having achieved the eradication ofsmallpox, promoting
mass immunization against a number of other preventable diseases, improving
mentalhealth;providingsafewatersupplies; andtraininghealth personnelofall
categories
Progresstowardsbetterhealththroughouttheworldalsodemandsmternational
cooperation in such matters asestablishinginternational standards for biological
substances, pesticides, and pharmaceuticals; fomndating environmental health
criteria;recommendinginternationalnonproprietarynamesfordrugs;administering
the International Health Regulations; revising the International Classification of
Diseases, Injuries, andCauses ofDeath; andcollectinganddisseminating health
statistical information
Further information on many aspects of WHO*s work is presented in the
Organization's publications.
Basic tests for
pharmaceutical dosage forms
This On*
YFGU-G8P-LES6
teftsdescrib€d indtismaiHial9ttintendedonlyto
verifytheidentityofpharmaceaticalpreparations.Tliey
shouldnotbeneedtorqplaoepharmacopoeialmonognplis.
Copyrightedmaterial
BASIC TESTS
FOR
HARMACEU
P TICAL
DOSAGE FORMS
I
I
WorldHealthOrganization
Geneva
1991
Copyrightedmatsrial
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ISBN924154418X (Nl^Classtncatlon:QV39)
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PublicationsoftheWortdHealthOrganizationenjoyoo|l|K#ltprotectioninaccordancewiththepnwlaianacf
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ofanyopinionwhatsoevaronttiepartoftheSecretariatoftheWorldHealthOrganizationconcerningthelegal
aMusofanycountiy,tenNoiytcityorareaorofitsauthorities,orconcerningthedelimitationofitsfrontiers
Thementionofspecificcompaniesorofcertainmanufacturers'productsdoesrwtimplythattheyareendorsed
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PRINTEDINENQLANO
90/8387-PHA/Ciays/QCML8QQ0
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i
Contents
1. Introduction 1
2- Recommendedfacilities 3
Generalrequirements 3
rurniture
Laboratoryservices 4
3. Inspection 5
4. Determinationofmeltingcharacteristics 6
5. Testprocedures 11
6. Equipment 111
7. Reagents 113
8. Indexofdosageforms 124
Acknowledgements 128
V
1. Introduction
lliebanc(siinp]]£wd)testsdescfibedintliu
dementsofqiulityassuranceinthephannaceuticalsupplysjrstem.theyhave
beendevisedwiththefollowingobjectives:
(a)toprovideasimpleandreadilyapplicablemethodforverifyingtheidentity
ofadrugsubstance,tisingalimitedrangeofeasilyavailablerea^^ts,when
thelabellingandphysicalattributesgiverisetodoubt;
(b)toprovideapracticablemeansofconfirmingtheidentityofadrug,whena
fullyequippedlaboratoryisnotavailable;
(c)toindicateifgrossdegradationhasoccurredincertainsubstancesthatare
knowntodecomposereadilyunderadverseconditions.
Basictestsarenot,inanycircumstances,intendedtoreplacetherequirements
ofTheIntenuahfuUPlumnaeopoeutorotherpharmacopoeialmonographs,
lliesegiveanassuranceofqualitywhereasbasictestsmerelyconfirmidentity.
InseveralEuropeancountries,simpletestshavealreadybeenendorsedbythe
nationalpharuMoeuticalassociationsforuseatperipherallevelsofdistribution
(wholesale premises, pharmacies) to verify the identity ofpharmaceutical
substances whenever the possibility ofconfusionarises and sometimes to
excludegrossdegradationoradulteration.
In1986,themanualBasictestsforpharmaceuticalsubstancefwaspublishedby
theWorldHealthOrganization.Itisnowcomplementedbythisvolume,which
containstestsfor150pharmaceuticaldosageforms,mostofwhichareincluded
WHO
inthe ModelUstofEsserMDrugs.'Eachofthetestsdescribedhasbeen
verifiedinatleastfourlaboratoriesindifferentcountries.Analogoustestsfor
fttitherdosageformsareinpreparationandwillbepublishedseparately.
Degradationduringstorageandtransportationis<Aparticularimportancein
tropicalcountries.Indeed,anexpirydatedeterminedforatemperateclimate
maybeinappropriateinatropicalregionevenwhenhighstandardsofpackag-
ing are meL For this reason,particular importance is accorded to visual
'TheInternationalPbttmueofOtu,thirdedition.Geneva,WorldHealdiOrguuution.Volume1:Generai
methodsofanalysis,1979.Vc^ume2:Qualityspedficatiom,1911.Voltune3:(^smUtyifeeifiaaioat,1988.
^'BWasHicOteTsetschfnoircpahlarRmeapcoeuntiSecrailess,ubNstaan7c9es6.,G1e9n9eava,WoddHealthOfgnizttum,1986.
X
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intpectioilofdosageforms,sincethisfrequentlyprovidesafirstvitalindication
ofdegndatloiLThudfoappliesincaseswheretherearereasonstosuspect
qualitydefiecttduetopoormamilaceure,tamperingorooonterfeiting.
BanctesiineednocbeoorriedombyjfoUyqualifiedphannaditso^
buttheyshouldbeperformedbyperMMitwidisomeundmtandingofanalyti-
calchemistrysuchasthatacquiredincoursesforpharmaceuticalassistants.
Severaltestsaredescribedformostpnpantiona.Notalloftheseneedtobe
appliedtoanyonesample.If,however,thereisanyreasontosuspectthatthe
productismislabelledorsubstandard,alltestsdescribedshouldbeperformed.
Bytheirnature,simplifiedtestscannotbetotallyreliable.Anadverseresult,
eveninonetest,shouldbetakenasawarningofpotentialunsuitabilityofadrug.
Inthese circumstances, afinal conclusionshould notbedrawn until afull
analyticalexaminationhasbeencarriedoutinaproperlyequippedquality
controllaboratory.
Theproposedtestsaresupplementedbyadviceonvisualinspectionandashort
descriptionofthenunimumfacilitiesandequipmentneededtocarryoutthe
work.ThereagentsneededfcMTtestingdosageformsarelistedatt^
publication.
Comments on the tests described are invited and should be addressed to:
Phannaceuticals»WorldHealthOrganization,1211Geneva27,Switzerland.
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2. Recommended facilities
Afullpharmacopoeialanalysisofadrugsubstanceorproduct can onlybe
performedinanadequatelyequippeddrugqualitycontrollaborator)^Recom-
WHO
mendationsaregiveninthetwenty-ninthreportofthe ExpertCommit-
tee on Specifications for Pharmaceutical Preparations'" on the design and
organizationofamodestqualitycontrollaboratory.Afirststeptowardsthe
devdopmentofsuchalaboratorywouldbetheestabliahmentoffacilitiesfor
carryingoutbasktests.
Q6MraliMiutoBimiitB
Tliewoilqplaceshouldbewellilluminated,prthnhtybyindirectnaturallight.
Itshouldbeair-condidoiiedorheatedaccordingtotheclimate.Inthelatter
case,aclosedconvectorheaterorradiatorshouldbechosenthatcanbeoperated
withoutHrehazard.Thedoorsshouldopenoutwardsandallfireandsafe^
regulationsshouldberespected.
Thefloorcoveringshouldbecontinuous,fireproofandeasilywashable.The
walls,thefurniture,andtheframesofthewindowsanddoorsshouldalsobe
easilywashable.Alltheseelementsshouldbeofaneutralcolour(preferably
whiteorpalebeige)tofacilitatetheevaluationofcolourreactions.
nimtture
Wock-benchesshouldbeplacedagiunstawallandshouldreceivenaturallight
ptt£sakfyftuindieieftside.Afumecupboaidoratabkwithaventilatorabove
itshouldbeinstalledinonecomeroftheroom.
Thetopsofwork-benchesshouldhaveawhiteorblackacid-resistantplastic
cover;aglassorceramictopwill resultinincreasedbreakageofglassware.
Unpaintedwoodensurfacesshouldbeimpregnatedwithsoftparaffin.Paints
orresinsusedtoprotectthesesurfacesshouldberesistanttodiluteacids.The
work-benches should be of a height that enables work to be undertaken
comfortablyinbothstandingandsittingpositions.Theyshouldincludeshelves
anddrawersthatarenotunnecessarilydeepandareadaptedtotheitemsthat
wiUbestmdinthem.ChairsshouldbestRM^builtandstable.
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