Microfluidic Device for the Crystallization of Organic Molecules in Organic Solvents

A microfluidic chip suitable for studying crystallization of organic molecules in organic solvents was developed. In this device,. supersaturation can be generated either. by thermal. gradient (i.e, when the crystallization solvent is not miscible With the continuous phase) or by mass transfer (When the crystallization solvent is partially miscible with the continuous phase) or both. The experimental setup allows the storage of up to 2000 droplets to get nucleation statistics and crystal growth rates under static conditions. Crystallization of eflucimibe in droplets of octanol generated in water was investigated by use of this experimental device. The results show that, at lower time scale, the first nucleation events result mainly from a heterogeneous nucleation process (due to the presence of impurities or to the octanol water interface itself). At higher time scales, the nucleation rate falls off, all the crystals appear in the droplet volume, and nucleation becomes homogeneous. This microfluidic device allows heterogeneous and homogeneous nucleation rate measurements to be performed in a single experiment. For ibuprofen crystallization in organic solvents partially miscible with water, no crystallization was observed, even at high time scales. Instead of crystallizing, the system undergoes a liquid-liquid phase separation. The liquid-liquid system obtained has a long lifetime, and contrary to what is usually observed, this metastable state does not promote nucleation of stable crystals.