(723b) Polymorph Screening of L-Glutamic Acid By Anti-Solvent Crystallization in Easy-to-Use Microfluidic Device

Most pharmaceuticals have polymorphs. Since different polymorphs exhibit distinct physical properties, such as solubility, bioavailability, density, mechanical properties, color and morphology, which result in difficulties in the downstream processing, including separation, handing and so on. Hence, it is crucial to control the crystallization of targeted polymorph. As an amino acid commonly used in pharmaceuticals and food, L-glutamic acid has two polymorphs: prismatic or granular shaped metastable α form and four different shaped stable β form, including need-, rod-, lozenge- and plate-shaped. In practical applications, α form has higher utilization efficiency. In previous work, to obtain a specific polymorph form of L-glutamic acid, the commonly adopted methods includes control of larger crystallization temperature difference, in quiescent and flow state through membrane crystallizers, adding amino acid additives, sonocrystallization and so on.

In this work, based on anti-solvent crystallization, solutions and antisolvent were loaded into separate syringes which were connected to channels. By varying the initial concentrations of solutions, temperature, and velocities of solution and antisolvent, the resulted crystals were flitered directly, and dried in an air oven. Then crystals were characterized by SEM and PXRD for morphology evaluation and form confirmation. The polymorph selectivity of L-glutamic acid was investigated. This method was simple in operation and low consumption was required. And the crystallization temperature was kept constant throughout the process. The results showed that this method was more flexible in the selectivity of L-glutamic acid polymorphs without other assistive technologies or additives which might introduce impurities.