Understanding, measurement and scale-up of secondary nucleation

One of main challenges in developing robust and efficient crystallisation processes is to control secondary nucleation. Secondary nucleation is critical for achieving optimal crystallisation outcomes, e.g. solid form, particle size, yield and purity, and yet it is very little understood, especially for pharmaceuticals. Following up on our previous GSK-Strathclyde collaboration on empirical secondary nucleation workflows, we aim to improve our fundamental understanding of mechanisms of secondary nucleation, devise new methods to assess and quantify these mechanisms using very small amounts of materials available early in the drug development, and develop a comprehensive secondary nucleation workflow to enable predictive scale-up of secondary nucleation from laboratory to pilot to plant scale. This will provide new tools for accelerated development, optimisation and scale up of crystallisation processes.