Application of functionalized magnetic silica nanoparticles for selective induction of three coumarin metastable polymorphs  

作　　者：Yiqing Chen Xin Huang Suping Ding Yaoguang Feng Na Wang Hongxun Hao 

机构地区：[1]National Engineering Research Center of Industrial Crystallization Technology,School of Chemical Engineering and Technology,Tianjin University,Tianjin 300072,China [2]Collaborative Innovation Center of Chemical Science and Engineering(Tianjin),Tianjin 300072,China [3]School of Chemical Engineering and Technology,Hainan University,Haikou 570228,China

出　　处：《Chinese Journal of Chemical Engineering》2022年第10期155-167,共13页中国化学工程学报（英文版）

基　　金：financial support from the National Natural Science Foundation of China(21908159);the Tianjin Natural Science Foundation(18JCZDJC38100)。

摘　　要：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 functional groups(-NH_(2),-COOH,-SH,-NCO)were prepared and coated on the substrate for inducing the crystallization of coumarin.Confined melt crystallization and microspacing sublimation crystallization methods were used to investigate the regulation mechanism.The results indicated that three metastable forms of coumarin can be obtained as pure components based on the combined influence of crystallization methods and functionalized nanoparticles.FormⅡcould be selectively obtained by microspacing sublimation crystallization on Fe_(3)O_(4)@SiO_(2)-SH substrates,and FormⅣcould be obtained by confined melt crystallization on Fe_(3)O_(4)@SiO_(2)-NCO substrates.FormⅢcould be obtained by further heating FormⅣcrystals to 52℃on Fe_(3)O_(4)@SiO_(2)-NCO substrates.Moreover,the polarized light microscopy 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 nanoparticle induced crystallization were comparatively investigated and the corresponding polymorphic selectivity mechanism was proposed.

关 键 词：POLYMORPH Functional nanoparticles Surface interactions Heterogeneous nucleation 

分 类 号：TQ460.1[化学工程—制药化工] TQ127.2[一般工业技术—材料科学与工程] TB383.1