Study Of Polymorphism Of Icariin And Crystallization-Induced Asymmetric Transformation Of Sanguinarine Methylate

Recently, as the increase of poorly soluble drugs among the newly developed drug candidates, the study of polymorphism of solid drugs attracted more and more attention. The first section of this paper investigated on the solid-state landscape of the active pharmaceutical ingredient of icariin(ICA). The solid-state properties were investigated by PXRD, SCXRD, TG, DSC, DVS and HSM. The equilibrium solubility was determined by HPLC.As previously reported, different chiral configurations of drugs may lead to significant differences in pharmacology and toxicology. Therefore, development of enantioselective preparation methods is very important in new drug discovery. The second section of this paper is the study on the crystallization-induced asymmetric transformation(CIAT) study of sanguinarine methylate. The CIAT was carried out by Viedma ripening method and using cooling crystallization to control the yield and ee outcomes. The enantiomeric excess(ee) was analyzed by CD.Two new anhydrous polymorphs and two hydrates were discovered in ICA polymorph screeening experiments. Notably, the single crystal structure of the marketed form was determined for the first time through a single crystal-single crystal transformations(SCSCTs) process, and the isomorphism phenomenon was observed among various organic solvates.Nucleophilic addition of sanguinarine chloride with sodium metholate gives alkanolamines under alkaline conditions. The single crystal structure of R/S and racemic compounds were determined for the first time by high throughput polymorph screening on sanguinarine methylate. Stochastic outcome with high ee% values, up to 100%, was observed under cooling crystallzation, while preferential chiral amplification was observed with Viedma ripening process.