The precise control of active pharmaceutical ingredient(API)crystal nucleation and polymorphism is a key consideration in pharmaceutical manufacturing.In this study,tunable nanoparticles were developed to regulate the nucleation process of coumarin.Magnetic silica nanoparticles with four different func-tional groups(—NH2,—COOH,—SH,—NCO)were prepared and coated on the substrate for inducing the crystallization of coumarin.Confined melt crystallization and microspacing sublimation crystalliza-tion methods were used to investigate the regulation mechanism.The results indicated that three meta-stable forms of coumarin can be obtained as pure components based on the combined influence of crystallization methods and functionalized nanoparticles.Form Ⅱ could be selectively obtained by microspacing sublimation crystallization on Fe3O4@SiO2—SH substrates,and Form Ⅳ could be obtained by confined melt crystallization on Fe3O4@SiO2—NCO substrates.Form Ⅲ could be obtained by further heating Form Ⅳ crystals to 52℃on Fe3O4@SiO2-NCO substrates.Moreover,the polarized light micro-scopy results also indicated that the introduction of nanoparticles could also increase the stability of the metastable crystalline forms of coumarin.Finally,the diffusion and surface dynamics during nanopar-ticle induced crystallization were comparatively investigated and the corresponding polymorphic selec-tivity mechanism was proposed.

Yiqing Chen;Xin Huang;Suping Ding;Yaoguang Feng;Na Wang;Hongxun Hao

National Engineering Research Center of Industrial Crystallization Technology,School of Chemical Engineering and Technology,Tianjin University,Tianjin 300072,China;Collaborative Innovation Center of Chemical.Science and Engineering(Tianjin),Tianjin 300072,China;School of Chemical Engineering and Technology,Hainan University,Haikou 570228,China

中国化学工程学报（英文版）

[1]Yiqing Chen;Xin Huang;Suping Ding;Yaoguang Feng;Na Wang;Hongxun Hao-.Application of functionalized magnetic silica nanoparticles for selective induction of three coumarin metastable polymorphs)[J].中国化学工程学报（英文版）,2022(10):155-167

microspacing,crystalliza

Application,functionalized,magnetic,silica,nanoparticles,induction,three,coumarin,metastable,polymorphs,precise,control,active,pharmaceutical,ingredient,API,nucleation,polymorphism,key,consideration,manufacturing,In,this,study,tunable,were,developed,regulate,process,Magnetic,four,different,groups,NH2,COOH,SH,NCO,prepared,coated,inducing,crystallization,Confined,melt,sublimation,methods,used,regulation,mechanism,results,indicated,that,forms,can,be,obtained,pure,components,combined,influence,Form,could,selectively,by,Fe3O4,SiO2,substrates,confined,further,heating,crystals,Moreover,polarized,light,scopy,also,introduction,increase,stability,crystalline,Finally,diffusion,surface,dynamics,during,induced,comparatively,investigated,corresponding,polymorphic,tivity,was,proposed

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