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

被引:30
作者
Lu, Jennifer [1 ]
Litster, James D. [1 ,2 ]
Nagy, Zoltan K. [1 ]
机构
[1] Purdue Univ, Sch Chem Engn, W Lafayette, IN 47907 USA
[2] Purdue Univ, Sch Ind & Phys Pharm, W Lafayette, IN 47907 USA
关键词
SOLUBILITY PARAMETERS; ORGANIC-MOLECULES; WATER; ACID; GAS; EMULSIONS; VEHICLE; GLYCINE; DEVICE; DRUG;
D O I
10.1021/acs.cgd.5b00150
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
In this work, an innovative experimental platform to study the nucleation behavior of ail 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 parameters show good agreement to literature values. However, the lactose nucleation rate increased more sharply with a supersaturation ratio than predicted by classical nucleation theory. The validation of aspirin nucleation studies from ethanol demonstrates the application of this newly design system for crystallization of relatively nonpolar organic molecules from nonaqueous solvents to give crystal with controlled attributes.
引用
收藏
页码:3645 / 3651
页数:7
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