Gravity as a Knob for Tuning Particle Size Distributions of Small Molecules

Pharmaceutical research and development and manufacturing can widely benefit from a microgravity environment. Although the use of microgravity to improve control over the size of protein crystals has been demonstrated, there have been few studies on the effect of gravity on small molecules. A hypergravity crystallization platform was developed as a rapid screening tool for the crystallization of small-molecule pharmaceuticals. This platform was used to show the effect of gravity on the nucleation and growth kinetics of l-histidine. Further experiments were conducted in the EasyMax reaction calorimeter with process analytical technology (PAT) tools to understand the kinetics of nucleation and growth and quantify the desupersaturation rate in the seeded cooling crystallization experiment.