Continuous Antisolvent Crystallization of Dolutegravir Sodium Using Microfluidics

Continuous antisolvent crystallization of Dolutegravir Sodium was studied using a novel device integrating the microfluidic continuous crystallizer and the agitated crystallizer. This study successfully minimized the risks of channel blockage during continuous crystallization by innovating an approach to isolate crystal nucleation from subsequent crystal growth. We systematically investigated the effects of the antisolvent content, channel width, and stirring speed on the particle size, the crystal size distribution (CSD), and the morphology of the crystals. By optimization of experimental parameters, crystals can be continuously obtained with small particle sizes (D-50 values of 5-10 mu m), narrow CSDs (widths of 4-7 mu m), and prismatic morphologies by this apparatus and approach. The particle sizes D-50 and CSDs of crystals are reduced by 30% and 60% at least, respectively, compared with values of the commercial sample. Small and uniform crystals are particularly desirable in the pharmaceutical industry, which can significantly improve drug solubility, bioavailability, corresponding pharmacokinetic performance, and the properties of the tablet.