药物晶型研究

2020/5/9,.,药物的多晶型研究,2020/5/9,.,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,2020/5/9,.,CrystalAsolidmaterialwhoseconstituentatoms,molecules,orionsarearrangedinanorderlyrepeatingpatternextendinginallthreespatialdimensions.PharmaceuticalcrystalsMostdrugsaredevelopedascrystallineStabilityProcessabilityIPprotection,什么是晶体？,2020/5/9,.,什么是多晶型？,Polymorphismistheabilityofasolidmaterialtoexistinmorethanoneformorcrystalstructure.PolymorphsSoldphaseSamechemicalcompositionDifferentmoleculararrangementsInpractice,weareinterestedinallthecrystallineandamorphousphasesforachemical/pharmaceutical,2020/5/9,.,2020/5/9,.,多晶型研究对药物开发的重要性,2020/5/9,.,药物多晶型研究的重要性,2020/5/9,.,2020/5/9,.,.,如何筛选和选择药物的新晶型,2020/5/9,.,2020/5/9,.,2020/5/9,.,晶型的化学和物理分析手段,2020/5/9,.,2020/5/9,.,2020/5/9,.,Experiencesharingonpolymorphscreeningsolventselection,2020/5/9,.,Thepurposeofpolymorphscreening,ForInnovatorcompanies-selecttheoptimalsolid-stateofAPIfordevelopment-studyrelevantpolymorphsforIPprotectionForCROcompaniesbasedonthecustomersneeds-toidentifyasmanynewpolymorphs(includesolvate/hydrate)andamorphousformaspossible-ortofindthemoststableform,2020/5/9,.,Themethodofpolymorphscreening,crystallization,crystallizationfromsolution(slurry,anti-solventprecipitation,Solvent-thermalheating/coolingSlow/fastprecipitationfromsaturatedsolutions),recrystallizationfromaneatcompound(thermalheating/cooling,grinding,andhighpressure),2020/5/9,.,polymorphscreeningcrystallizationfromsolution,degreeofsupersaturationandTemperatureareconsideredasthedrivingforceofcrystallisationdiversesolventsresultinthediscoveryofmorepolymorphs,2020/5/9,.,crystallizationfromsolutionSolventselection,SlurryAnti-solventprecipitationSolvent-thermalheating/coolingexperimentsSlow/fastprecipitationfromsaturatedsolutionsmethod,2020/5/9,.,crystallizationfromsolutionrationalexperimentaldesign,LimitedresourceHowtofindasmanynewpolymorphsandamorphousformaspossibleAPIpropertiesdifferentsolubilityinthesolventpoorsolubilityorgoodsolubilitySolventpropertiesPolarity-differentsortofsolvents(alcohols,ethers,esteretc.)BoilingpointFreezingpointToxicitymiscibility,？,2020/5/9,.,Slurrysolventselection,Makesurethesampleissuspensionsolvent/mixedsolventssolubilityispoor,2020/5/9,.,Anti-solventprecipitationsolventselection,Preparesolventgoodsolubility,Anti-solventselection,Poorsolubility,polarity,miscibility,miscibilityWaterDMFHeptaneACN1,4-DioxaneMTBEDMSO,2020/5/9,.,Solvent-thermalheating/coolingexperiments,changetemperaturesupersaturationgoodsolubilitySolventselectionsolubilityvarieswiththetemperaturefreezingpointofthesolvent,2020/5/9,.,Slow/fastprecipitationfromsaturatedsolutionsmethod,EvaporatethesolventsupersaturationSlow/fastrateofcrystallizationSolventselectionlowboilingpoint,2020/5/9,.,SummarySolventselection,keypointofthemethods