Measurement and Evaluation of the Crystallization Kinetics of l‑Asparagine Monohydrate in the Ternary l‑/d‑Asparagine/Water System

Growth kinetics of l-asparagine monohydrate in racemic aqueous solutions as well as nucleation, growth, and dissolution kinetics of the same enantiomer crystallized from pure l-asparagine solutions are measured, and the kinetic parameters are estimated applying a recently developed shortcut method. The corresponding experimental procedure is based on a small number of preferential (seeded) cooling crystallizations where the crystal size distribution is monitored with an online microscope. Afterward, image analysis yields the transient particle size evolution of initially provided crystals, from which the response of the solid phase to the liquid-phase driving force can be extracted. Subsequently, parameter estimation is carried out applying these data together with the information on concentration and composition of the liquid phase to discriminate between different model approaches. The kinetics are validated finally with independent experiments to evaluate their quality. It is proven that growth kinetics of l- and d-asparagine monohydrate from water are identical. In contrast, it can be shown and quantified that growth kinetics from racemic and enantiopure solutions of asparagine differ significantly from each other. The corresponding calculation of the driving force of enantiomeric systems is discussed in detail by means of ternary phase diagrams.