Understanding, measurement and scale-up of secondary nucleation

开发稳健和高效的结晶工艺的主要挑战之一是控制二次成核。二次成核是实现最佳结晶结果的关键，例如固体形态、颗粒大小、产率和纯度，但人们对其知之甚少，特别是对药物。继GSK-Strathclyde之前在经验二次成核工作流程上的合作之后，我们的目标是提高对二次成核机制的基本了解，设计新的方法来使用药物开发早期可用的极少量材料来评估和量化这些机制，并开发全面的二次成核工作流程，以实现从实验室到中试到工厂规模的二次成核的预测性放大。这将为加速开发、优化和扩大结晶工艺提供新的工具。

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.