Crystallization of alpha-lactose monohydrate in a drop-based microfluidic crystallizer

• Published in: Chemical engineering science 2007-09, Vol.62 (17), p.4802-4810
• Main Authors: Dombrowski, Richard D., Litster, James D., Wagner, Norman J., He, Yinghe
• Format: Article
• Language: English
• Subjects: Applied sciences; Chemical engineering; Crystallization; Crystallization, leaching, miscellaneous separations; Exact sciences and technology; Microfluidics; Nucleation; Particle formation; Pharmaceuticals; Product design
• ISSN: 0009-2509; 1873-4405
• DOI: 10.1016/j.ces.2007.05.033

A microfluidic process for producing crystals of controlled size by confining the crystallization within drops is demonstrated. The process consists of a drop producing stage which segments the mother liquor into monodisperse drops followed by crystallization in a temperature controlled tubular crystallizer. The process is implemented to produce lactose crystals with significantly narrower crystal size distribution (CSD) as compared with crystals produced in a stirred bulk crystallizer. By controlling the drop size and initial supersaturation the mean crystal size can be controlled. The distribution of the number of crystals per drop and the CSD are measured as a function of supersaturation at temperatures between 20 and 40 ∘ C for 150 and 300 μ m drops. In the case where drops contain only one crystal, a very narrow CSD is obtained with a coefficient of variation of crystal size as low as 7%. The crystallization of lactose in a microfluidic tubular crystallizer is modeled by treating nucleation in drops as a Poisson process with a nucleation rate based on classical nucleation theory. Experimental results are in good agreement with predictions from a Poisson process model over the range of temperatures, supersaturations and drop sizes tested.