Fluid Dynamic and Heat Transfer Simulations of Solid Hollow Fiber Cooling Crystallizer for Continuous Synthesis of Drug Nanoparticles

The study illustrates for the first time a computational fluid dynamics (CFD)-based heat transfer model for the novel solid hollow fiber cooling crystallizer (SHFCC) that can produce drug nanoparticles in a continuous and controllable manner. In the SHFCC device, a mixture of water and ethylene glycol is circulated through the shell side of a solid hollow fiber module to rapidly cool the drug solution flowing in the hollow fiber lumen side to produce rapid temperature reduction-induced drug crystals. In this study, a three-dimensional model of an SHFCC device was first constructed using the software GAMBIT and then was exported to the CFD software-FLUENT after the meshing and optimization process, to understand and optimize hydrodynamic and heat transfer characteristics of this device theoretically. The variation of lumen-side flow rate was investigated using CFD to explore the influences of residence time, flow rate, and cooling temperature on the crystal size distribution. Variations of the shell-side temperature and flow rate were also simulated to reveal the heat transfer efficiency of the SHFCC module and understand the phenomenon of temperature reduction-induced precipitation and crystal formation. Actual experimental results were also obtained to investigate the accuracy and usefulness of the CFD model. This research suggested the feasibility and advantages of a combination of CFD simulation with experiments to optimize and control drug crystallization process in the novel SHFCC device to meet the needs of modern pharmaceutical industry.