Post-breakage Crystal Regeneration: Multiple Breakage Sites, Growth Kinetics, and Effects on Mass Production

Post-breakage crystal growth is obscure. Recently, form I paracetamol (PCM) crystals, broken to expose their internal cleavage plane (010), grew back into their original shapes through “regeneration.” This work reports on regeneration in crystals with multiple breakage sites, regeneration growth kinetics, and regeneration’s process optimization potential. Single PCM crystals with two breakage sites grew into their original shapes in ethanol, with a rate twice that of crystals with one breakage site. In a surface integration-limited regime, PCM regeneration in ethanol followed the kinetic equation G = (34.1 ms^–1) exp (−38.2 kJmol^–1/RT)(S – 1)^1.80. With a higher pre-exponential factor and lower activation energy, regeneration is indicated to proceed significantly faster than regular growth across different temperatures and concentrations. A modified “two-crystal” setup enabled the comparison of mass growth rates between regenerating and unbroken crystals during PCM evaporative crystallization in acetone, evaporative crystallization in ethanol, and isothermal crystallization in ethanol. In these cases, regenerating crystals grew faster by 36 ± 8 wt %, 75 ± 19 wt %, and 94 ± 34 wt %, respectively. Projections to multi-crystal systems indicated that crystallization processing times could be lowered by up to 42%, 60%, and 65% for the respective cases. These findings offer improvements for crystallization process modeling and optimization.

This experimental study investigates postbreakage crystal regeneration of form I paracetamol (PCM) in ethanol and acetone. PCM with two breakage sites regenerated at a rate twice that of one-site regeneration. PCM regeneration kinetics in ethanol were formulated, indicating significantly faster rates than unbroken crystal growth. A modified “two-crystal” setup showcased enhanced mass growth via regeneration, promising to improve crystallization processes.