Nucleation Studies of Active Pharmaceutical Ingredients in an Air-Segmented Microfluidic Drop-Based Crystallizer

• DOI: 10.1021/acs.cgd.5b00150
• Publication Date: 2015-06-16T15:54:57Z
• Authors: Jennifer Lu; James D. Litster; Zoltan K. Nagy
• Keywords: 01 natural sciences; 0104 chemical sciences

In this work, an innovative experimental platform to study the nucleation behavior of an active pharmaceutical ingredient (API) using a gas-segmented flow produced by a microfluidic T-junction device with fine perfluoroalkoxy alkane (PFA) tubing is presented. In the experiments, a continuous airflow was used to segment the supersaturated liquid phase into nearly monodispersed droplets (with a coefficient of variance about 15% of the drop size distribution) at the T-junction. As the API molecules have relatively low gas/solvent partition coefficients, mass transfer between phases is effectively inhibited. Nucleation then occurred within the drops in the temperature-controlled capillary crystallizer. By treating the probability of crystal nucleation in each drop as a nonstationary Poisson process, the effect of process conditions on lactose and aspirin nucleation was studied. In lactose nucleation studies, the Poisson rate process effectively captures the nucleation behavior, and the estimated nucleation pa...