Crystal nucleation in adroplet based microfluidic crystallizer

Abstract

The study presented in this paper deals with the determination of eflucimibe nucleation rate in a droplet based microfluidic crystallizer. The experimental device allows the storage of up to 2000 monodispersed droplets to get nucleation statistics and crystal growth rates under static conditions. Supersaturation was generated by quenching the droplets down to 273 or 293 K. To determine the nucleation kinetics of eflucimibe, the number of appearing crystals is recorded as a function of time. At low time scale, it was found that eflucimibe in the droplets containing active centers (impurities) crystallizes first and thus yields a rapid initial rate. At higher time scale, once all the droplets containing impurities have crystallized, leaving only the droplets that are free of impurities, the nucleation rate falls allowing the determination of the homogeneous nucleation rate. The crystal–solution interfacial energy found in this system σ=3.12 mJ m−2 is in good agreement with the previously published results. Using the crystalnucleation and the growth rate determined experimentally, simulations were performed using a Monte Carlo method. Even if this method correctly predicts the number of droplets that remains empty during the experiments, it was not possible to predict correctly the number of crystals per drop obtained experimentally. The relationship between the growth and nucleation rates and the resultant number of crystals per drop is likely to be complex and dependent on a number of system parameters. The failure of the model may be attributed either to an overestimation of the crystal growth rate or to an enhancement of the nucleation rate due to the presence of seed crystals.