药物晶型研究ppt课件

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