(416a) A Competitive Kinetic Model for Polymorph Nucleation

A competitive kinetic model for polymorph nucleation is developed in this work to describe the time evolution of two different polymorphic cluster size distributions in a supersaturated solution controlled by the agglomeration and disruption of the solutes. Although there is only one type of the solute molecules, it is assumed that the agglomerated solute clusters due to the Brownian motion are divided into two types – A form and B form, which resemble the structures and morphologies of the different mature polymorphs and eventually lead to the formation of two polymorphic crystals. Recently, Shiau and Lu (2009) developed a discrete binary random disruption kernel to account for dissolution of the solute clusters. In this work, a disruption kernel is incorporated into the proposed model to account for gradual dissolution of the solute clusters smaller than a critical nucleus size due to the thermodynamic instability. By fitting the experimental induction period data and the final measured weight fractions of eflucimibe polymorphs with the proposed model, the agglomeration and disruption rate constants for two polymorphs are recovered. It is found that the developed model is satisfactory to describe the competitive mechanism of nucleation for eflucimibe polymorphs in a supersaturated solution.

Ref.

[1] Shiau, L.D., Lu, Y.F., 2009. Modeling solute clustering in the diffusion layer around a growing crystal. J. Chem. Phys. 130, 094105.