ApplicationofProcessAnalyticalTechnology(PAT)

inCrystallizationProcessofChiralDrugs

過程分析技術在手性藥物結晶中的應用1Presenter:NingxinZhan,SuyingWang,HaiwuYang

2017.05.081.Introduction

2.Experimentalsection3.Resultsanddiscussion

24.ConclusionCATALOGChiralitythesamemolecularweightandmolecularstructuredifferentinspatialarrangementofatomssimilartoourleftandrighthands31.IntroductionWhyischiralitysoimportantindrugdevelopment?Thetwoenantiomersofachiraldrugoftenhavedifferentactivities.Inthemostcases,onlyoneoftheenantiomershaspharmacologicalactivity,theotheroneoftenhavenoorpossiblyevenaharmfuleffect.41.Introduction1.Introduction

WhatisPAT?PAT--spectroscopictechnologiesusedinon-linereal-timemeasurementandcharacterisationofcriticalprocessandproductqualityvariables.5ObtainrawmaterialsObtainrawmaterialsMixactiveandexcipeintsPresstabletsMixactiveandexcipeintsPresstabletsCrystallizationCrystallizationconventionalapproach--labbasedPATapproach--processbased,atlineoron-lineendofphasetestingofquality,toreducetheriskinmovingtothenextstagecontinuouslyormorefrequentlytestqualityduringeachphase,toremovetheriskinmovingtothenextstageDifferencebetweenconventionalapproachandPATapproach?1.IntroductionInsitutechniques(PAT):Nanosonic,2Dvision,Turbidity,ATRFTIR6Nanosonic2DVisionTurbidityATR-FTIR2.Experimentalsection7howtoobtainpuredrugsinindustrialproduction?SeparationbychiralchromatographySeparationofenantiomersMethodsCrystallizationAsymmetricsynthesisEnzymaticseparationsimpleeconomicalChiraldrugValsartanBinaryphasediagram(DSC)Ternarysolubilityphasediagram

solubility

determinationRacemiccompoundEutecticcomposition(S:R=90:10)PreferentialcrystallizationTurbidity2Dvisionsystem(PAT)FiltrationDryProduct8ATR-FTIR2.Experimentalsection2.Experimentalsection9ATR-FTIRTurbidity2DVision3.Resultsanddiscussion10IntensityWavenumberWavenumberIntensity溶劑背景峰ValsartanWavenumberIntensityATR-FTIR3.Resultsanddiscussion11MultivariableconcentrationmodelComparisonbetweenpredictedandactualvalueofsolutionR2=0.9997123.Resultsanddiscussion3.Resultsanddiscussion13beforedryingafterdrying3.Resultsanddiscussionturbidityseeds144.ConclusionConclusion1、ATR-FTIRwasusedtorealizeon-linemeasurementofconcentrationinreal-time,sothatwecandeterminewhetherit'ssupersaturation.2、2Dvisionsystem