药物晶型研究ppt课件

2020/4/30,.,1,药物的多晶型研究,2020/4/30,.,2,提纲,什么是晶体，多晶型？多晶型研究对药物开发的重要性如何筛选和选择药物的新晶型多晶型的主要分析手段晶型筛选实验的经验分享-溶剂选择,2020/4/30,.,3,CrystalAsolidmaterialwhoseconstituentatoms,molecules,orionsarearrangedinanorderlyrepeatingpatternextendinginallthreespatialdimensions.PharmaceuticalcrystalsMostdrugsaredevelopedascrystallineStabilityProcessabilityIPprotection,什么是晶体？,2020/4/30,.,4,什么是多晶型？,Polymorphismistheabilityofasolidmaterialtoexistinmorethanoneformorcrystalstructure.PolymorphsSoldphaseSamechemicalcompositionDifferentmoleculararrangementsInpractice,weareinterestedinallthecrystallineandamorphousphasesforachemical/pharmaceutical,2020/4/30,.,5,2020/4/30,.,6,多晶型研究对药物开发的重要性,2020/4/30,.,7,药物多晶型研究的重要性,2020/4/30,.,8,2020/4/30,.,9,.,10,如何筛选和选择药物的新晶型,2020/4/30,.,11,2020/4/30,.,12,2020/4/30,.,13,晶型的化学和物理分析手段,2020/4/30,.,14,2020/4/30,.,15,2020/4/30,.,16,Experiencesharingonpolymorphscreeningsolventselection,2020/4/30,.,17,Thepurposeofpolymorphscreening,ForInnovatorcompanies-selecttheoptimalsolid-stateofAPIfordevelopment-studyrelevantpolymorphsforIPprotectionForCROcompaniesbasedonthecustomersneeds-toidentifyasmanynewpolymorphs(includesolvate/hydrate)andamorphousformaspossible-ortofindthemoststableform,2020/4/30,.,18,Themethodofpolymorphscreening,crystallization,crystallizationfromsolution(slurry,anti-solventprecipitation,Solvent-thermalheating/coolingSlow/fastprecipitationfromsaturatedsolutions),recrystallizationfromaneatcompound(thermalheating/cooling,grinding,andhighpressure),2020/4/30,.,19,polymorphscreeningcrystallizationfromsolution,degreeofsupersaturationandTemperatureareconsideredasthedrivingforceofcrystallisationdiversesolventsresultinthediscoveryofmorepolymorphs,2020/4/30,.,20,crystallizationfromsolutionSolventselection,SlurryAnti-solventprecipitationSolvent-thermalheating/coolingexperimentsSlow/fastprecipitationfromsaturatedsolutionsmethod,2020/4/30,.,21,crystallizationfromsolutionrationalexperimentaldesign,LimitedresourceHowtofindasmanynewpolymorphsandamorphousformaspossibleAPIpropertiesdifferentsolubilityinthesolventpoorsolubilityorgoodsolubilitySolventpropertiesPolarity-differentsortofsolvents(alcohols,ethers,esteretc.)BoilingpointFreezingpointToxicitymiscibility,？,2020/4/30,.,22,Slurrysolventselection,Makesurethesampleissuspensionsolvent/mixedsolventssolubilityispoor,2020/4/30,.,23,Anti-solventprecipitationsolventselection,Preparesolventgoodsolubility,Anti-solventselection,Poorsolubility,polarity,miscibility,miscibilityWaterDMFHeptaneACN1,4-DioxaneMTBEDMSO,2020/4/30,.,24,Solvent-thermalheating/coolingexperiments,changetemperaturesupersaturationgoodsolubilitySolventselectionsolubilityvarieswiththetemperaturefreezingpointofthesolvent,2020/4/30,.,25,Slow/fastprecipitationfromsaturatedsolutionsmethod,EvaporatethesolventsupersaturationSlow/fastrateofcrystallizationSolventselectionlowboilingpoint,2020/4/30,.,26,SummarySolventselection,keypointoftheme