lecture3_scaleup design and analysis

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1、Lecture3ScaleupDesignandAnalysisBackground-Objective-Formulation/processfactorsStatisticalConcepts-Confounding-InteractionScaleupDesign-Objective-Factorialdesign-Centralcompositedesign-PlackettandBurmandesign-OtherdesignsAcsleupAnalysis-Tableofcontrastcoefficie

2、nts-Yate’salgorithmAnExampleOUTLINEBackgroundObjectiveToensurethataproductionbatchcanmeettheUSP/NFstandardsfortheidentity,strength,quality,andpurityofthedruygproductwhenitisscaledupfrom-alaboratorybatch-asmall-scaleproductionbatchSpecificObjectives-Toidentify,e

3、valuate,andoptimizecriticalformulationand/orprocessfactorsofthedrugproduct-TomaximizeorminimizeexcipientrangesFormulationfactorsTABLE4.3.1CriticalFormulationFactorsforTabletFormulationFormulationfactorDescriptionDiluentBulkingagent(lactose)“Glues”powederBindert

4、ogethertofromgranules(acaciacellulose)LubricantPreventfrictionandwear(magesiumGlidantstearate)improveflow(talc)PreventAntiadherentgranulationsormaterialsfromstickingtofacesatpunchesanddiewalls(talc)DisintegrantCausestabletstobreakapart(starch)ProcessfactorsBlen

5、derUseofpreblenddingGranulatingwaterlevelGranulatingblendingprocedureGranulatingblendingtimeWetscreensizeDryingconditionsDryscreensizeSlughardnessRollspeedDegreeofcompactionLubricantblendingtimeResponseVariablesTABLE4.3.3ResponseVariablesofTabletManufacturingPa

6、rticlesizeEjectionforceFlowDissolutionBulkdensityWeightvariationMoistureDisintergrationHardnessFriabilityStatisticalConceptsConfoundingConfoundingeffectsaredefinedaseffects,whicharecontributedbyvariousfactors,thatcannotbeseparatedbythedesignunderstudyInteractio

7、nTheinteractioneffectbetweenfactorsisdefinedasthejointeffectcontributedbymorethanonefactorAnexampleAnexample-FactorialexperimentTABLE4.2.1FactorialExperimentRunX1X2X3X4X1X2X3X4Response1++++++Y12++--++Y23+-+---Y34+--+--Y45-++---Y56-+-+--Y67--++++Y78----++Y8Anexa

8、mple–FactorialexperimentInteractionbetweenx1andx2FactorX2-11-1FactorX11Interactionbetweenx3andx4FactorX4-11-1FactorX31Y7,Y8Y5,Y6Y3,Y4Y1,Y2Y2,Y8Y4,Y6Y3,Y5Y1,Y7Anexample–Facto