Spherulitic growth strategy for solvent-induced formation of spherical L-carnosine products

Solvent effects on L-carnosine spherical aggregates were studied. • Reduced (001) solvent-crystal interaction promotes spherulitic growth. • Tip defects trigger non-crystallographic branching and spherulitic growth. • The spherulitic crystals exhibited superior flow properties. L-carnosine, a biologically active dipeptide with significant antioxidant properties, typically crystallizes in a needle-like habits that result in poor flowability and low bulk density, posing significant challenges for downstream processing. This study provides a new strategy for the preparation and optimization of spherical L-carnosine crystals. Systematic solvent screening identified dimethyl sulfoxide (DMSO) as the optimal antisolvent, enabling the formation of dense, uniform spherulites. The effects of main crystallization parameter on the morphology and properties of the spherical crystals were explored and the optimal crystallization conditions were determined. Molecular dynamics simulations and experimental analyses reveal that DMSO selectively reduces the solvent-crystal interaction energy on the (001) crystal face, accelerating growth at the crystal tips and triggering non-crystallographic branching. Compared to the raw material and spherical agglomerates, the spherulites show a 3.6-fold and 2.7-fold increase in bulk density, respectively. More importantly, they exhibit excellent flowability (Carr's index 14.4% vs. 47.8% and 39.2%; Hausner's ratio 1.16 vs. 1.92 and 1.47), highlighting the primary advantage of the spherulitic growth strategy. This work provides a mechanistic understanding of spherulitic growth and offers a practical route to enhance the powder properties of L-carnosine. Download: Download high-res image (223KB) Download: Download full-size image Solvent‑dependent morphology evolution and non‑crystallographic branching mechanism in L‑carnosine spherulitic crystallization.