The effect of solvents on crystal regeneration

Abstract

Solvents play a pivotal role in crystallisation, affecting crystal growth and properties. This study investigates the regeneration behaviour of paracetamol crystals in ethanol, tetrahydrofuran, and acetone using both evaporative and isothermal crystallisation setups, coupled with a custom MATLAB-based edge detection algorithm for facet-specific growth rate measurements. Regeneration was observed in all solvents, with the fastest rate observed in ethanol (0.07 mm h⁻¹), followed by THF (0.03 mm h⁻¹), and acetone (0.02 mm h⁻¹) at a supersaturation ratio of 1.10. In all cases, regeneration was driven by rapid growth of the (0 1 0) facet, restoring crystals to their original shapes. Crystal shape influenced the regeneration time, with a rapid initial phase comprising 8–15% of total regeneration time. Molecular dynamics simulations were utilised to quantify solvent–crystal interactions, showing that not only do the inherent solvent properties play a role but also the solubility of paracetamol significantly affects crystal regeneration.