Polymorph formation studied by 3D nucleation simulations. Application to a yellow isoxazolone dye, paracetamol, and L-glutamic acid.
Knowledge of the nucleation and growth behavior of polymorphs is vital in a variety of industrial applications. With the aid of the growth probability method the nucleus size is obtained as a function of the driving force for crystallization by simulating the growth probability of clusters of various sizes. From these values the cluster interfacial energy can be computed, allowing for the determination of the nucleation rate. The simulations show that nucleation of the metastable form of a yellow isoxazolone dye dominates at higher driving forces while below a certain driving force the stable form nucleates. Two other compounds show dominant nucleation of their stable form, even at extreme driving forces. This is in accordance with experimental findings for all these compounds. The growth probability method is therefore a promising indicator for polymorph nucleation behavior.
Deij
Menno A
MA
IMM Solid State Chemistry, Faculty of Science, Radboud University Nijmegen, Toernooiveld 1, NL-6525 ED Nijmegen, The Netherlands.
ter Horst
Joop H
JH
Meekes
Hugo
H
Jansens
Peter
P
Vlieg
Elias
E