Intergrowth of two aspirin polymorphism observed with Raman spectroscopy

Abstract

Abstract Polymorphism of aspirin, one of the important pharmaceutical compounds, crystallizes in two similar structures (form I and form II). This similarity causes the intergrowth structure containing both form I domain and form II domains in the same crystal. The intergrown crystal is often observed, however, the crystallization process of the intergrown crystal was unclear. In order to reveal the crystallization process, we performed in situ observation of the growth using the crystal obtained immediately after the nucleation with Raman spectroscopy. The temporal change of Raman spectral pattern showed that form I grew on the surface of the form II seed crystal. In addition, we investigated spatially where the growth of form I was initiated. It was suggested that the crystal growth rate of form I on form II surface depends on the local surface supersaturation. We concluded that the crystallization of the intergrowth of aspirin was caused by the crystal that was form II at the nucleation being covered by form I as the growth proceeded.