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D . M.

BRAHMANKAR
Ph'D'
M'Sc',
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VALLABHPRAKASHAN
290 AND PHARMACOKINETICS
BIOPHARMACEUTICS
BIOAVAILABILITY
ANDBIoEeurvALENcE 291
Acqte PharmacologicResponse
Despiteattemptsto standardizethe test performance,the in vitro dissolu-
. - Wtt"n bioavailabilitymeasurementby pharmacokinetic methodsis dif- tion techniqueis still by no meansa perfect approach. The efforts are
fibulq-lnaccurate or nonreproducible,an acute pharmacologic effect such mainly aimed at mimicking the environmentoffered by the biological
as changein ECG or EEG readings,pupil diameter,etc. is relatedto the system.
time cburseof a given drug. Bioavailabilitycan then be determinedby
constructionof pharmacologiceffect-timecurve as well as dose-respgnse There are severalfactorsthat must be consideredin the design of a
graphs. The method requiresmeasurementof responsesfor at least 3 dissolutiontest. They are:
biological half-lives of the drug in order to obtaifr-a lobd estimateof' l. Factorsrelating to the dissolutionapparatzssuchas-the design,
AUC. the size of the container(severalmL to severalliters), the shapeof the
A disadvantageof this method is that the pharmacologicresponse container(round bottomedor flat), natureof,agitation(stining, rotatingor
tends to be more variable and accuratecorrelationbetweenmeqsured oscillating methods),speed of agitation, performanceprecision of the
responseand drug availablefrom the formulationis difficult. Moreover, apparafts,etc.
the observedresponsemay be due to an activemetabolitewhoseconcen- 2. Factors relating to the dissolution fluid such as----composition
tration is not proportionalto the concentrationof parentdrug responsible (water, 0.lN HCl, phosphatebuffer, simulatedgastric fluid, simulated
for the pharmacologiceffect. intestinalfluid, etc.), viscosity,volume (generallylargerthan that needed
to completelydissolvethe drug undertest), temperature(generally37oC)
Therapeutic Response and maintenanceof sink (drug concentrationin solutionmaintainedcon-
Theoreticallythe most definite,tliis methodis basedon observingthe stantat a low level) or nonsink conditions(gradualincreasein the drug
clinical respohseto p drug formulali\n given to patientssuffering from concentrationin the dissolutionmedium).
diseasefor which it 1isintendedto bd used. A major drawbackof this
3. Processparameterssuch as method of introductionof dosage
methodis that quantitationof observedresponseis too improperto allow
for reasonableassessrpurt of relative bioavailabilitybetweentwo dosage form, samplingtechniques,changingthe dissolutionfluid, etc.
forms of the samedrug. The dissolutionapparatushasevolvedgraduallyand considerablyfrom
a simplebeakertype to a highly versatileand fully automatedinstrument.
Drug Ilissolution Rate and Bioavailability The devicescan be classifiedin a numberof ways. Basedon the absence
The physicochemicalproperty of most drugs that has greatestinflu- or presenceof sink conditions,thereare rwo principaltypesof dissolution
ence on their absorptionch_aracteristicsfrom the GIT is dissolutionrate. apparatus:
The best way of assessingtherapeuticefficacy of drugs with a slow
l. Closed-compartment apparatus : It is basicallya limited-vol-
dissolutionrate is rn vpo determinationof bioavailabilitywhich is usually
ume apparatusoperatingunder nonsinkconditions. The dissolutionfluid
done whenevera new formulation is to be introducedinto the market.
is restrainedto the size of the container,e.g. beakertype apparatus.
However, monitoring batch-to-batchconsistencythrough use of such in
vrvo testsis extremelycostly,tediousand time consuming'besides expos- 2. Open-compartmentapparatus: It is the one in which the dos-
ing the healthysubjectsto hazardsof drugs. It would thereforebe always age form is containedin a columnwhich is broughtin continuouscontact
desirableto substitutethe in vivo bioavailabilitytestswith inexpensivein with fresh,flowing dissolutionmedium(perfectsink condition).
vitro methods. The simple in vitro disintegrationtest is unreliable. The A third type called as dialysis systems are used for very poorly
best ai'ailable tool .todry which can at least quantitativelyassureabout aqueoussoluble drugs for which maintenanceof sink conditionswould
- the biologic availability of a *ug from its formulation r rrs in vitro otherwiserequire large volume of dissolutionfluid. Only the official
dissolution [est. methodswill be discussedherebriefly.
' In Vitro Dru€ DissolutionTesting Midels ' Rotating BasketApparatus(Apparatus1)
For dii'tinvttto teistto be useful,it must predictthe in vivo behaviorto It is basicallya closed-comparfrnent,beakertype apparatuscomprising
such an extent.that in vivo bioavailability test need not be performed. of a eylindrical glass vesselwith hemisphericalbottom of one liter capac-
tr Errcntla13ot Phyilcll Phlrmrccut|Gt -OrS SuDrahmanyrrn
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cl Blobhemlstry-P GunduRlo
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IJ Introductlon to Pharm6cology-PC Oandlyrlnd SK Kulklrnl
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Heafth Educatlonand CommunltyPharmacy-Dandlya,Zdfetg. Z q
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