Surface Accelerates Crystal Nucleation: The Case of Molnupiravir

Molecules at the liquid/vapor interface have different properties, such as faster mobility and special packing structure, which can potentially affect crystal nucleation. However, the surface effect varies significantly among different small organic molecules and the underlying mechanism is still poorly understood. Herein, the effect of the surface on the crystal nucleation dynamics has been investigated in the glass-forming liquid molnupiravir (MPV) by measuring the crystal nucleation rates at the surface and in the bulk. It was found that the surface of the glass-forming liquid MPV could significantly enhance the nucleation rate by around six orders of magnitude without a polymorphic change. In comparison to water and acetaminophen with a surface enhancement factor of Js/Jv ≈ 105, the larger surface enhancement factor of MPV indicates a higher similarity between the nucleated crystal structure and the molecular packing at the surface. Our work enriches the surface-enhanced nucleation systems, which are beneficial to further understanding the stability of amorphous drugs.