Spherical Crystallization of Glycine from Monodisperse Microfluidic Emulsions

• Published in: Crystal growth & design 2012-08, Vol.12 (8), p.3977-3982
• Main Authors: Toldy, Arpad I, Badruddoza, Abu Zayed M, Zheng, Lu, Hatton, T. Alan, Gunawan, Rudiyanto, Rajagopalan, Raj, Khan, Saif A
• Format: Article
• Language: English
• Subjects: Condensed matter: structure, mechanical and thermal properties; Cross-disciplinary physics: materials science; rheology; Equations of state, phase equilibria, and phase transitions; Exact sciences and technology; Growth from melts; zone melting and refining; Materials science; Methods of crystal growth; physics of crystal growth; Physics; Solid-solid transitions; Specific phase transitions
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/cg300413s

Emulsion-based crystallization to produce spherical crystalline agglomerates (SAs) is an attractive route to control crystal size during downstream processing of active pharmaceutical ingredients (APIs). However, conventional methods of emulsification in stirred vessels pose several problems that limit the utility of emulsion-based crystallization. In this paper, we use capillary microfluidics to generate monodisperse water-in-oil emulsions. Capillary microfluidics, in conjunction with evaporative crystallization on a flat heated surface, enables controllable production of uniformly sized SAs of glycine in the 35–150 μm size range. We report detailed characterization of particle size, size distribution, structure, and polymorphic form. Further, online high-speed stereomicroscopic observations reveal several clearly demarcated stages in the dynamics of glycine crystallization from emulsion droplets. Rapid droplet shrinkage is followed by crystal nucleation within individual droplets. Once a nucleus is formed within a droplet, crystal growth is very rapid (