Study of polymorphic control in an ethanol-water binary solvent

Abstract

Three polymorphs of l-Citrulline crystals, anhydrate (Form α, γ and δ) and pseudo polymorph (dihydrate), were confirmed. In this study, polymorphic control of l-Citrulline was attempted by changing the ethanol concentration in ethanol-water binary solvents. First, each polymorph of l-Citrulline crystals was added to the prepared ethanol-water binary solvents and samples which were obtained chronologically were measured by XRD. Also, the crystal sizes and shapes in transformation were observed by microscope. Then, polymorphs of the crystals after transformation were determined by XRD pattern. As a result, the transformation from dihydrate to anhydrate was observed by adding dihydrate crystals to the ethanol-water binary solvent. Similarly, the transformation from anhydrate to another anhydrate was observed. Especially in the case of adding dihydrate, the existences of all polymorphs were confirmed by adjusting ethanol-water binary solvent. According to the results, it was revealed that polymorphic transformation was affected by the trace amount of water contained in ethanol-water binary solvent. Moreover, transformation from dihydrate to anhydrate was constructed with three phases, dissolution of dihydrate, nucleation and growth of anhydrate. Therefore, the solution-mediated polymorphic transformation was supposed to be a key mechanism for this transformation.