# The Effect of Solvents on the Crystal Morphology of Isosorbide Mononitrate and Its Molecular Mechanisms

## TL;DR

This study explores how solvents affect the crystal shape of isosorbide mononitrate and explains the underlying molecular mechanisms.

## Contribution

The study introduces a modified attachment energy model and uses molecular dynamics to analyze solvent effects on crystal growth.

## Key findings

- C6H14 accelerates crystal growth but does not significantly change morphology.
- Solvent interactions with crystal faces were analyzed using RDF and MSD methods.
- Modified attachment energy calculations guide industrial crystallization processes.

## Abstract

In this work, the modified attachment energy model was used to predict the crystal morphology of isosorbide mononitrate (ISMN) in the dichloromethane (CH2Cl2) solvent system and dichloromethane-n-hexane (CH2Cl2-C6H14) mixed solvent system. The solvent effect can significantly affect the crystal morphology, which can profoundly impact both the drug’s physicochemical properties and the subsequent technological treatment process. In addition, the interactions between solvent molecules and crystal faces were investigated using molecular dynamics simulation, and radial distribution function (RDF) analysis was performed to determine the types of interactions. The structural parameter S was introduced to characterize the roughness of each crystal surface; the change in the CH2Cl2 diffusion coefficient before and after the addition of C6H14 was analyzed using mean square displacement (MSD). The calculation results of the modified attachment energy from the two solvent systems revealed that C6H14 could accelerate crystal growth, while the crystal morphology was not greatly affected, which is of some significance as a guide for the industrial crystallization process.