药物晶型研究课件

1、药物的多晶型研究,1,学习交流PPT,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,学习交流PPT,Crystal A solid material whose constituent atoms,molecules, or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions. Pharmaceutical crystals Most drugs are devel

2、oped as crystalline Stability Processability IP protection,什么是晶体？,3,学习交流PPT,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 phase Same chemical composition Different molecular arrangements In practice, we are interested in

3、all the crystalline and amorphous phases for a chemical/pharmaceutical,4,学习交流PPT,5,学习交流PPT,多晶型研究对药物开发的重要性,6,学习交流PPT,药物多晶型研究的重要性,7,学习交流PPT,8,学习交流PPT,9,学习交流PPT,如何筛选和选择药物的新晶型,10,学习交流PPT,11,学习交流PPT,12,学习交流PPT,晶型的化学和物理分析手段,13,学习交流PPT,14,学习交流PPT,15,学习交流PPT,Experience sharing on polymorph screening solvent

4、 selection,16,学习交流PPT,The purpose of polymorph screening,For Innovator companies - select the optimal solid-state of API for development -study relevant polymorphs for IP protection For CRO companies based on the customers needs - to identify as many new polymorphs (include solvate / hydrate) and am

5、orphous form as possible - or to find the most stable form,17,学习交流PPT,The method of polymorph screening,crystallization,crystallization from solution (slurry, anti-solvent precipitation , Solvent-thermal heating/cooling Slow/fast precipitation from saturated solutions),recrystallization from a neat

6、compound (thermal heating/cooling, grinding , and high pressure ),18,学习交流PPT,polymorph screening crystallization from solution,degree of supersaturation and Temperature are considered as the driving force of crystallisation diverse solvents result in the discovery of more polymorphs,19,学习交流PPT,cryst

7、allization from solution Solvent selection,Slurry Anti-solvent precipitation Solvent-thermal heating/cooling experiments Slow/fast precipitation from saturated solutions method,20,学习交流PPT,crystallization from solution rational experimental design,Limited resource How to find as many new polymorphs a

8、nd amorphous form as possible API properties different solubility in the solvent poor solubility or good solubility Solvent properties Polarity-different sort of solvents (alcohols, ethers, ester etc.) Boiling point Freezing point Toxicity miscibility,？,21,学习交流PPT,Slurry solvent selection,Make sure

9、the sample is suspension solvent/mixed solvents solubility is poor,22,学习交流PPT,Anti-solvent precipitation solvent selection,Prepare solvent good solubility,Anti-solvent selection,Poor solubility,polarity,miscibility,miscibility Water DMF Heptane ACN 1,4-Dioxane MTBE DMSO,23,学习交流PPT,Solvent-thermal he

10、ating/cooling experiments,change temperature supersaturation good solubility Solvent selection solubility varies with the temperature freezing point of the solvent,24,学习交流PPT,Slow/fast precipitation from saturated solutions method,Evaporate the solvent supersaturation Slow/fast rate of crystallization Solvent selection low boiling point,25,学习交流PPT,SummarySolvent selection,key point of the method select