In-vitro and In-vivo- Correlation study (IVOVC)

Correlations between in vitro and in vivo data (IVIVC) are often used during pharmaceutical development

1. Dr. Anuj Malik
Professor
MM College of Pharmacy,
MM (Deemed to be University), Mullana,
Ambala (HARYANA)
In-vitroand In-vivo
Correlations

2. COURSE OUTCOME
1.Tounderstandtheprincipleunderlyingtechniquesof
Biopharmaceuticsandpharmacokineticsindrugdeliveryatthe
pre-clinicalstage
2.Toknowhowtodeterminethephysicochemicalpropertiesof
druganddrugconcentrationofpharmaceuticaldosageform
3.Toknowhowpharmacokineticparameterresultsareanalyzed
4.Toutilizesuchknowledgeindesigningofformulationstoaddress
potentialpharmacokineticsissuesofdrug

3. Learning Outcomes
Aftercompletionofthisthischapterthestudents
willbeable-
⚫TounderstandtheconceptIn-vitroandIn-vivo
Correlations.
⚫TounderstandthemechanismofIn-vitroandIn-vivo
Correlations.
⚫Tounderstandtheprincipalunderlyingandclinical
applicationofIn-vitroandIn-vivoCorrelations

4. Learning Outcomes
Aftercompletionofthisthischapterthestudents
willbeable-
⚫TounderstandtheconceptIn-vitroandIn-vivo
Correlations.
⚫TounderstandthemechanismofIn-vitroandIn-vivo
Correlations.
⚫Tounderstandtheprincipalunderlyingandclinical
applicationofIn-vitroandIn-vivoCorrelations

5. Introduction
Correlations between in vitro and in vivo data (IVIVC) are often used during
pharmaceutical development
⚫inordertoreducedevelopmenttimeandoptimizetheformulation.
⚫Agoodcorrelationisatoolforpredictinginvivoresultsbasedoninvitro
data.
⚫IVIVCallowsdosageformoptimizationwiththefewestpossibletrialsin
man,fixesdissolutionacceptance
⚫TheFDAdefinesIVIVCas“apredictivemathematicalmodeldescribing
therelationshipbetweenaninvitropropertyofanextendedrelease
dosageform(usuallytherateorextentofdrugdissolutionorrelease)
andarelevantinvivoresponse,e.g.,plasmadrugconcentrationor
amountofdrugabsorbed.”

6. Level-IVIVC

7. Level A-IVIVC
Acorrelationofthistypeisgenerallylinearandrepresentsapoint-to-point
relationshipbetweeninvitrodissolutionandtheinvivoinputrate(e.g.,theinvivo
dissolutionofthedrugfromthedosageform).Inalinearcorrelation,theinvitro
dissolutionandinvivoinputcurvesmaybedirectlysuperimposableormaybe
madetobesuperimposablebytheuseofascalingfactor.Nonlinearcorrelations,
whileuncommon,mayalsobeappropriate.Alternativeapproachestodevelopinga
LevelAIVIVCarepossible.WhateverthemethodusedtoestablishaLevelAIVIVC,
themodelshouldpredicttheentireinvivotimecoursefromtheinvitrodata.In
thiscontext,themodelreferstotherelationshipbetweeninvitrodissolutionofan
dosageformandaninvivoresponsesuchasplasmadrugconcentrationoramountof
drugabsorbed.

8. Level B-IVIVC
ALevelBIVIVCusestheprinciplesofstatisticalmoment
analysis.Themeaninvitrodissolutiontimeiscompared
eithertothemeanresidencetimeortothemeaninvivo
dissolutiontime.ALevelBcorrelationdoesnotuniquely
reflecttheactualinvivoplasmalevelcurve,becausea
numberofdifferentinvivocurveswillproducesimilar
meanresidencetimevalues.

9. Level C-IVIVC
ALevelCIVIVCestablishesasinglepointrelationshipbetweenadissolution
parameterforexample,t50%,percentdissolvedin4hoursanda
pharmacokineticparameter(e.g.,AUC,Cmax,Tmax).ALevelCcorrelation
doesnotreflectthecompleteshapeoftheplasmaconcentration-timecurve,
whichisthecriticalfactorthatdefinestheperformanceofproducts.Inaddition
tothesethreelevels,acombinationofvariouslevelsCisalsodescribed:A
multipleLevelCcorrelationrelatesoneorseveralpharmacokineticparameters
ofinteresttotheamountofdrugdissolvedatseveraltimepointsofthe
dissolutionprofile.

10. IVIVC-Significance
ALevelAcorrelationdefinesalinearrelationshipbetweeninvitroand
invivodatasothatmeasurementoftheinvitrodissolutionratealoneis
sufficienttodeterminethepharmacokineticprofileinvivo.Aftera
propervalidation,IVIVCpredictstheinvivobioavailabilityresultsfrom
invitrodissolutiondata,andthissimulationreflectstheinvivobehavior
ofthevariousformulations.

11. Conclusion
LevelAIVIVCsdefinetherelationshipbetweenaninvitrodissolutioncurveandan
invivoinput(absorption)profile.A,LevelAcorrelationshouldalwaysbetrieda
prioriinordertohaveatoolthatallowsacompleteinvivopredictionfromaninvitro
dissolutioncurveandthusacceleratesthedevelopmentandassistsinsome
regulatoryaspects(SUPAC,Scale-upandPost-ApprovalChanges).Thecorrelation
qualitydependssolelyonthequalityofthedata.Asinvivodataarenowwell
standardized,themaineffortmustbedirectedtotheinvitrodata.Various
apparatusandmediashouldbetestedandassessedintermsoftheirinvivo
predictability.Theusershouldalwaysbeawareofthelimitsofthemethodandof
theconfidenceofitsprediction.

12. Thanks