(274d) Crystallization in Surfactant-Free Monodisperse Emulsions

In this poster we address the need for economical production of crystals of controlled size, shape, and polymorph in the pharmaceutical and related industries. Solution crystallization from surfactant-free, monodisperse emulsions was investigated as a method for producing lactose crystals of a narrow crystal size distribution (CSD). Isothermal lactose crystallization experiments were carried out at 20 C, 30 C and 40 C using a microfluidic T-junction to form uniform drops between 100 to 300 micron diameter, followed by a temperature controlled plug-flow crystallizer to prevent drop coalescence. The CSD from drops that contain only one crystal has a coefficient of variation (CV) as low as 7.0%, while the CV of the entire crystal population produced from crystallization in monodisperse emulsions is typically between 16-20%, compared to 40% obtained from bulk crystallization. The CV of single crystals decreases as supersaturation increases as the crystals approach the maximum possible size in the drops. The CV of crystals in drops that contain multiple crystals is constant as a function of supersaturation and is much higher than the CV of the single crystals. The fraction of drops containing a single crystal increases with temperature, but the increase is not large enough to yield a narrow CSD. The interfacial energy and activation energy for lactose nucleation, calculated using classical nucleation theory, were 7.26 mJ/m^2 and 188 kJ/mol, respectively. A population balance model incorporating Monte Carlo methods to model stochastic nucleation and crystal growth rate dispersion is developed to model, optimize, and control the particle formation process. Methods to trigger nucleation and control the formation of one crystal per drop are presented.