(654f) Enabling Continuous Antisolvent Crystallization Using Hollow Fibre Membranes

Crystallization is a fundamental separation technology used in the pharmaceutical industry for purification and isolation of particulate solids. Accurate nucleation and growth process control are vitally important but difficult in traditional crystallization methods and suffer from drawbacks such as high energy consumption in large-scale productions [1]. Emerging innovative crystallization technologies introduce significant improvements to process design and control to attain products with specific properties [2].

Amongst the incipient technologies, membrane crystallization has progressed significantly in recent years with promising applications for crystallization control and process intensification. Until recently membranes’ application was mainly focused on wastewater treatment or saltwater desalinization through membrane distillation which involves removing solvent (mostly, water) from the lumen-side to the shell-side. Newer applications of membranes in crystallization processes can be found more regularly in the literature for the continuous synthesis of nano-drug particles by antisolvent crystallization [3], continuous synthesis of polymer-coated drug particles [4], and emulsification [5], amongst others.

In the work described in this proposal continuous antisolvent crystallization was undertaken through a cross-filtration setup, using porous hollow fiber membranes, which was adapted as shown in Figure 1. The crystallization of NaCl crystals served as a proof-of-concept to demonstrate particle size control and attain a narrow crystal size distribution (CSD) through the manipulation of solution to antisolvent flowrate ratio and membrane structure, i.e., pore size and surface area.

REFERENCES

[1] X. Jiang, Y. Shao, L. Sheng, P. Li, and G. He, “Membrane Crystallization for Process Intensification and Control: A Review,” Engineering, no. xxxx, 2020, doi: 10.1016/j.eng.2020.06.024.

[2] Z. Gao, S. Rohani, J. Gong, and J. Wang, “Recent Developments in the Crystallization Process: Toward the Pharmaceutical Industry,” Engineering, vol. 3, no. 3, pp. 343–353, 2017, doi: 10.1016/J.ENG.2017.03.022.

[3] J. C. W. Fern, S. Ohsaki, S. Watano, and R. Pfeffer, “Continuous synthesis of nano-drug particles by antisolvent crystallization using a porous hollow-fiber membrane module,” Int. J. Pharm., vol. 543, no. 1–2, pp. 139–150, 2018, doi: 10.1016/j.ijpharm.2018.03.025.

[4] D. Chen, D. Singh, C. Jin, K. Sirkar, and R. Pfeffer, “Continuous production of polymer coated drug crystals, submicron particles, and nanoparticles by hollow fiber membrane-based cooling and anti-solvent crystallization,” Adv. Mater. - TechConnect Briefs 2017, vol. 3, pp. 52–55, 2017.

[5] C. Charcosset, I. Limayem, and H. Fessi, “The membrane emulsification process—a review,” J. Chem. Technol. Biotechnol., vol. 79, no. 3, pp. 209–218, Mar. 2004, doi: 10.1002/jctb.969.