Mechanochemical cocrystallisation in a simplified mechanical model: decoupling kinetics and mechanisms using THz-TDS

Abstract

Mechanical compaction plays a dual role in mechanochemical cocrystallisation, simultaneously influencing reaction rates and crystallisation pathways. Here, we introduce a simplified single-punch compaction model that allows systematic variation of force (5–40 kN) and dwell time under controlled conditions. Using terahertz time-domain spectroscopy (THz-TDS) combined with a dual kinetic fitting strategy (free-fit vs. fixed-n Avrami models), we decouple kinetic rate constants from mechanism changes and map force-dependent transitions in a TPMA–PE cocrystallisation system. Increasing compaction force from 5 kN to 40 kN reduced the fitted rate constant k_free from 0.2147 to 0.1195 h⁻ⁿ, while increasing the Avrami exponent n_free from 0.6409 to 1.2057. This suggests a force-driven transition from diffusion-limited or heterogeneous nucleation to more interface-controlled one-dimensional crystallisation. These findings provide new mechanistic insight into how mechanical energy inputs shape solid-state transformations, with implications for process optimisation in pharmaceutical manufacturing, especially in continuous production environments where compaction profiles vary dynamically.