Understanding polymorph crystallization is important due to the different properties, such as bioavailability or crystal shape, exhibited by the different crystal forms. In this work, we present a model, based on population balance equations, describing the unseeded crystallization by cooling of substances exhibiting multiple polymorphs, where each new primary nucleus of each polymorph forms according to a stochastic process, while secondary nucleation and crystal growth are deterministic. The model explains why multiple polymorphs can be present in a suspension during the early stages of crystal formation and growth, as observed experimentally in recent literature. Moreover, the model allows us to investigate in detail the effect and importance of the kinetics as well as the operating conditions on the stochastic behavior of the system, elucidating how they impact the evolution of the solid-phase composition after the first nucleation event.

• Georgia Institute of Technology (Georgia Tech)
• ETH Zurich / Bristol-Myers Squibb Company

• Modeling

1. crystallization
2. Crystals
3. Mathematical methods
4. modeling
5. Nucleation
6. Research Article
7. Supersaturation