Nucleation behavior of isosorbide 5-mononitrate revealed from metastable zone widths by combining nucleation theory model and molecular simulation

Isosorbide 5-mononitrate (5-ISMN) crystal has a needle-like morphology with an aspect ratio greater than 20, which brings great inconvenience to post-processing and storage processes. However, it is difficult to solve the above problem due to the missing study of 5-ISMN nucleation process in solution. The main purpose of this article is to study the nucleation behavior of 5-ISMN by the metastable zone width (MSZW) experiment, the semi-empirical Nyvlt model and the modified Sangwal' s theory in n-propanol, n-butanol, n-propyl acetate and n-butyl acetate systems. The results indicated that when the saturation temperature decreases or the cooling rate increases, the value of interfacial energy (gamma) increases, while the value of pre-exponential factor (A) basically unchanged, which was strongly related to the properties of the solvent itself. The nucleation rate (J) was found to be competitively related to the saturation temperature (T-0) and chemical potential (delta mu). Meanwhile, molecular simulations revealed that the value of nucleation rate J and solute-solvent interactions were closely related. (c) 2022 Elsevier B.V. All rights reserved.