(113b) Optimization of Drop-Based Microfluidic Crystallization of Alpha-Lactose Monohydrate

Microfluidic devices hold many promises for applications, particularly in the field of drug delivery, where there are strict requirements on crystal size, crystal size distribution (CSD), and morphology. In traditional bulk crystallization, due to uncertain nucleation, slow growth rates and growth rate dispersion, many materials tend to yield broad CSD. Experimental studies were performed to optimize the operation conditions of surfactant-free drop-based microfluidic crystallization to maximize the fraction of single crystals and narrow the CSD of lactose. Monodisperse lactose solution drops were formed in a T-shaped microfluidic device using 300 µm capillary teflon tubing where kerosene acted as the continuous oil phase and lactose solution as the supersaturated aqueous phase. The non-optimized isothermal process consisted of one crystallization step carried out at 25°C for 24 hours, the optimized thermal process on the other hand consisted of two nucleation-growth cycles. The nucleation step was carried out at 25°C for 4 hours, and the growth step was carried out at 40°C for 8 hours. By controlling nucleation and growth rates as well as initial supersaturations, the mean crystal size and the fraction of single crystals were controlled. The crystallization of lactose in a microfluidic tubular crystallizer was modeled using Monte Carlo simulations and the Poisson model with a nucleation rate based on the classical nucleation theory.