Advanced Spectroscopic Techniques for Lactose Crystallization Analysis: Investigating Water Participation in Crystal...

We provide an integrated strategy for scientists seeking to comprehend the participation of water in amorphous lactose crystallization and its impact on crystal morphology across different water activity (a_w) levels and temperatures. Low-field nuclear magnetic resonance (LF-NMR) and segmented magnetic resonance imaging (MRI) results unveil a cyclic migration process of water involving a gas-liquid-solid migration during sorption and crystallization stages within the analyzed samples. The corrected terahertz time-domain spectroscopy (THz-TDS) spectra indicate that water molecules have a perturbative effect and actively participate in lactose vibration formation. Comparison between theoretical and experimental Raman spectra reveals a tendency for β-lactose anhydrate to isomerize into α-lactose anhydrate upon insertion of water, leading to the formation of α-lactose monohydrate. The lactose crystal morphologies influenced by water from amorphous to crystalline state include α-/β-lactose anomers → mixed α-/β-lactose anhydrate crystals and α-lactose monohydrate → α-lactose monohydrate and β-lactose anhydrate → α-lactose monohydrate and α-lactose anhydrate unstable → recrystallized α-lactose monohydrate. These findings have broad implications for fundamental science and practice, enabling precise control over lactose-based products.