Microfluidic Continuous Seeded Crystallization: Extraction of Growth Kinetics and Impact of Impurity on Morphology

Abstract

We describe a continuous microfluidic system for seeded crystallization of small organic molecules, such as active pharmaceuticals, and demonstrate integration with in situ detection tools for determining the size and polymorphic form of the crystals. This integrated device is used to extract growth kinetics, as a screening platform for process parameter effects and optimization, and to gain insight into the fundamentals of the crystallization process. In addition, the microfluidic system also allows studies of additive effects on the crystal habit. The method is demonstrated with growth kinetics for α-, β-, and γ-forms of glycine along with the effects upon the morphology of adding glutamic acid and methionine.