Continuous slug-flow tubular crystallization has been explored by several Research Article groups in academia and industry as a way to produce crystals while having low capital equipment costs. In this crystallization type, slugs of slurry and gas consecutively travel through a tube, with a high degree of mixing and temperature uniformity within each slug. This article presents an experimental system for slug-flow tubular crystallization that employs a spatial temperature profile and directed non-contact ultrasonication to induce primary nucleation to enable the generation of a wide variety of crystal size distributions. The crystal size distributions are compared for data collected from a full-factorial experimental design (27 experiments in total) to predictions from a population balance model that includes the effects of ultrasonication on primary nucleation. This population balance model for tubular crystallization is the first that incorporates the effects of ultrasonication and dissolution on the crystal size distribution. The crystal size distributions are reasonably consistent with the model, within 20% prediction error, for all experiments in which the spatial temperature profile is monotonically decreasing and at low to moderate supersaturation. Potential causes for weaker agreement for other experiments are discussed.

• Massachusetts Institute of Technology (MIT) (MIT)

• Modeling

1. Continuous crystallization
2. continuous manufacturing
3. modeling
4. Pharmaceutical crystallization
5. population balance modeling
6. Research Article
7. Slug-flow crystallization
8. Tubular crystallization