(683d) A Stochastic Model of Primary Nucleation of Polymorphs

Polymorphism is a crucial feature of crystals, with particular importance in the fine chemical and pharmaceutical industry, since different polymorphs have different physical and chemical properties, such as solubility and crystal structure. Crystal nucleation is known to be a stochastic phenomenon; however, the implications of its statistical nature for the order of formation of the polymorphs (Ostwald’s rule of stages) have not yet been explored. Similarly, the role of stochastic nucleation in polymorphs transformation has not been thoroughly investigated either.

Based on large experimental evidence, and building upon previous theoretical work, we have developed a stochastic model of primary nucleation of multiple polymorphs from a clear solution, accounting also for growth, dissolution, and secondary nucleation. With this model, one can simulate and qualitatively study the interplay of all phenomena acting in the system - often coupled and not directly measurable - and their role in determining detection times and polymorphs transformation. Assessing such relationships and the mechanisms underlying them would allow to not only gain a deeper understanding of polymorphism, but also to better design and optimise the production processes of polymorphs.