Optimization of a crystallization by online FBRM analysis of needle-shaped crystals

Abstract

In this contribution, the FBRM probe is used to investigate a crystallization of needle-shaped particles to develop a crystallization that can deliver product within the required quality attributes. The crystallization under study is that of CDP323-2, a small-molecule prodrug antagonist. As the particles do not show a spherical shape habit, particular care has to be taken when interpreting FBRM chord length distributions. Case-specific chord length distribution (CLD) properties are defined for needle-shaped particles to study primary and secondary nucleation, as well as crystal growth and breakage during the crystallization. Results show the crystallization of CDP323-2 to be characterized by a very rapid longitudinal growth after nucleation. During the initial stages of cooling, crystal growth kinetics dominate secondary nucleation, but this tendency is reversed for the lower temperatures of the cooling profile. The FBRM is shown to be a powerful tool that can bring valuable insight, even for the crystallization of nonspherically shaped particles. © 2011 American Chemical Society.