Crystallization of l-glutamic acid under microfluidic conditions and levitation

Abstract

To gain control over polymorph selection is a pivotal issue in the pharmaceutical, food, and fine chemical industry. However, the mechanisms which affect polymorph selectivity are still not fully chartered. In the present study, we demonstrated the complex crystallization behavior of l-glutamic acid under microfluidic conditions. Amorphous intermediates occur in the early stages of the experiment, which undergo a series of aging steps – such as aggregation/coalescence, growth, or shrinking – before the stable β-polymorph forms. Experiments indicated that the attachment of amorphous particles partly feds crystal growth. This complex mechanism, which was observed under laminar flow conditions, might lead to the preferential formation of a flower-like shape of β-l-glutamic acid. We accompanied these experiments, which were characterized by laminar flow-conditions, with experiments under acoustic levitation in which crystal formation takes place under constant but gentle convection in an evaporating droplet. In these experiments, a similar phenomenon was also observed. However, when crystallization was conducted in a conventional stirred-tank, a mixture of α-form and β-form was formed, characterized by a prism, needle- and plate-like morphologies instead of the distinct flower-like in earlier experiments. This demonstrates that gentle flow conditions, such as a laminar flow in a microfluidic device, preferentially leads to a complex flower-like shape than conventional approaches in a stirred tank.