Nonclassical Crystallization of the L‑Tartrate Salt of Cyamemazine

This study investigates the nonclassical crystallization of cyamemazine L-tartrate, a kryptoracemic salt of the antipsychotic drug cyamemazine. The crystallization pathway was studied via slurry conversion of a suspension of cyamemazine and L-tartaric acid in 2-propanol to the salt. Notably, the system transitioned through an intermediate droplet phase, which subsequently coalesced to form a dense phase. Both intermediate phases exhibited liquid crystalline character when observed under a polarized light microscope. The droplets demonstrated birefringence and a distinct Maltese cross extinction pattern, confirming their liquid crystalline nature. The dense phase revealed a fan-like texture when isolated and examined between glass slides. Comprehensive analyses of the intermediate droplet phase and the dense phase were conducted using solution ¹H nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and in situ stimulated Raman scattering (SRS) imaging. The combination of imaging and analytical techniques employed in this study allowed for elucidation of the nature and composition of the intermediate phases involved in the crystallization process.