1、资料仅供参考,不当之处，请联系改正。2022-6-9提纲提纲F什么是晶体，多晶型？F多晶型研究对药物开发的重要性F如何筛选和选择药物的新晶型F多晶型的主要分析手段F晶型筛选实验的经验分享-溶剂选择资料仅供参考,不当之处，请联系改正。2022-6-9Crystal A solid material whose constituent atoms,molecules,or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions.Pharmaceutical crystal
2、s Most drugs are developed as crystallineStabilityProcessabilityIP protection 什么是晶体？什么是晶体？资料仅供参考,不当之处，请联系改正。2022-6-9什么是多晶型？什么是多晶型？ Polymorphism is the ability of a solid material to exist in more than one form or crystal structure. Polymorphs Sold phaseSame chemical compositionDifferent molecular ar
3、rangements In practice, we are interested in all the crystalline and amorphous phases for a chemical/pharmaceutical资料仅供参考,不当之处，请联系改正。2022-6-9资料仅供参考,不当之处，请联系改正。2022-6-9多晶型研究对药物开发的重要性资料仅供参考,不当之处，请联系改正。2022-6-9药物多晶型研究的重要性药物多晶型研究的重要性资料仅供参考,不当之处，请联系改正。2022-6-9资料仅供参考,不当之处，请联系改正。2022-6-9资料仅供参考,不当之处，请联系改正。如
4、何筛选和选择药物的新晶型资料仅供参考,不当之处，请联系改正。2022-6-9资料仅供参考,不当之处，请联系改正。2022-6-9资料仅供参考,不当之处，请联系改正。2022-6-9晶型的化学和物理分析手段晶型的化学和物理分析手段资料仅供参考,不当之处，请联系改正。2022-6-9资料仅供参考,不当之处，请联系改正。2022-6-9资料仅供参考,不当之处，请联系改正。2022-6-9Experience sharing on polymorph screening solvent selection资料仅供参考,不当之处，请联系改正。2022-6-9The purpose of polymorp
5、h screeningFor Innovator companies - select the optimal solid-state of API for development -study relevant polymorphs for IP protectionFor CRO companies based on the customers needs - to identify as many new polymorphs (include solvate / hydrate) and amorphous form as possible - or to find the most
6、stable form 资料仅供参考,不当之处，请联系改正。2022-6-9The method of polymorph screeningcrystallizationcrystallization from solution (slurry, anti-solvent precipitation , Solvent-thermal heating/coolingSlow/fast precipitation from saturated solutions)recrystallization from a neat compound (thermal heating/cooling, g
7、rinding , and high pressure )资料仅供参考,不当之处，请联系改正。2022-6-9polymorph screening crystallization from solutiondegree of supersaturation and Temperature are considered as the driving force of crystallisation diverse solvents result in the discovery of more polymorphs资料仅供参考,不当之处，请联系改正。2022-6-9crystallizatio
8、n from solution Solvent selectionSlurryAnti-solvent precipitation Solvent-thermal heating/cooling experiments Slow/fast precipitation from saturated solutions method SolventVisual solubility (mg/mL)MeOHEtOHIPA1-ButanolACNMEKMIBKEtOAciPrOAcMTBE2-MeTHFDMFNMPDMSOCH2Cl2Toluene1,4-DioxaneHeptaneTHFAceton
9、eWater资料仅供参考,不当之处，请联系改正。2022-6-9crystallization from solution rational experimental designLimited resource How to find as many new polymorphs and amorphous form as possible API properties different solubility in the solvent poor solubility or good solubility Solvent properties Polarity-different sor
10、t of solvents (alcohols, ethers, ester etc.) Boiling point Freezing point Toxicity miscibility ？资料仅供参考,不当之处，请联系改正。2022-6-9Slurry solvent selectionMake sure the sample is suspension solvent/mixed solvents solubility is poor资料仅供参考,不当之处，请联系改正。2022-6-9Anti-solvent precipitation solvent selection Prepare
11、 solvent good solubilityAnti-solvent selectionPoor solubilitypolaritymiscibility miscibility Water DMF Heptane ACN 1,4-Dioxane MTBE DMSO资料仅供参考,不当之处，请联系改正。2022-6-9Solvent-thermal heating/cooling experimentschange temperature supersaturation good solubility Solvent selection solubility varies with the
12、 temperature freezing point of the solvent 资料仅供参考,不当之处，请联系改正。2022-6-9Slow/fast precipitation from saturated solutions method Evaporate the solvent supersaturation Slow/fast rate of crystallization Solvent selection low boiling point solventboiling pointDMF 152.8 CDMSO189 CNMP202 C资料仅供参考,不当之处，请联系改正。2022-6-9SummarySolvent selectionkey point of the method select appropriate solvent different solubility in the solventsolvent propertiesmiscibilitybetween solvents Polarityboiling pointfreezing pointToxicity
