Solution-Mediated Polymorphic Transformation of L-Carnosine from Form II to Form I

Abstract

In this study, L-carnosine was chosen as the model compound to systematically study solution-mediated polymorphic transformation by online experiment and theoretical simulation. Form II, a new polymorph of L-carnosine, was developed using an antisolvent crystallization method. The properties of form I and form II L-carnosine were characterized by powder X-ray diffraction, polarizing microscope, thermal analysis, and Raman spectroscopy. In order to explore the relative stability, the solubility of L-carnosine form I and form II in a (water + DMAC) binary solvent mixture was determined by a dynamic method. During the solution-mediated polymorphic transformation process of L-carnosine in different solvents, Raman spectroscopy was employed to detect the solid-phase composition of suspension in situ, and the gravimetric method was used to measure the liquid concentration. In addition, the effect of the solvent on the transformation process was evaluated and analyzed. Finally, a mathematical model of dissolution–precipitation was established to simulate the kinetics of the polymorphic transformation process based on the experimental data. Taking the simulation results and the experimental data into consideration, the controlling step of solution-mediated polymorphic transformation was discussed.