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. Form II could be selectively obtained by microspacing sublimation crystallization on Fe

3

O

4

@SiO

2

—SH substrates

and Form IV could be obtained by confined melt crystallization on Fe

3

O

4

@SiO

2

—NCO substrates. Form III could be obtained by further heating Form IV crystals 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.