关键词: 有机膜, 溶析结晶, 传质, 过程强化, 液膜更新

Abstract:

Antisolvent crystallization is an environmentally friendly and highly efficient crystallization method that plays an irreplaceable role in the fields of crystal production of thermosensitive substances and low solubility systems. However, the key problems of the conventional antisolvent crystallization include uncontrollable rapid nucleation and poor time and space uniformity of the supersaturation. In this work, we propose to use polyethersulfone(PES) organic hollow fiber membrane to provide a uniform and stable interface for mass transfer between the antisolvent and the crystallization solution, which can achieve accurate mass transfer mixing and process intensification. Antisolvent is uniformly permeated through the organic membrane under the pressure difference, and an antisolvent liquid film layer can be formed on the outer surface of the membrane. Through the liquid film renewal mechanism, the millimeter-scale macroscopic mixing is transformed into the submicron-scale micromixing, which can realize the uniform distribution of supersaturation. At the same time, the existence of the liquid film can prevent the membrane surface from directly contacting with the crystallization solution, effectively solving the problem of membrane fouling caused by heterogeneous nucleation adhesion. In the experiment, the permeate flux changes immediately and has a highly consistent linear response with the change of flow rate after a periodic change in the shell-side flow rate, confirming the accuracy and sensitivity of organic membrane to precisely control the mass transfer process. The PES hollow fiber membrane can remain stable performance on permeation rate after repeated use for more than 24 times. The crystal product obtained by the organic membrane control process has a more regular morphology and more concentrated particle size distribution than the conventional dropwise addition crystallization under the same antisolvent adding rate. Therefore, the antisolvent crystallization controlled by organic membrane has a stable performance on its precise mass transfer process and antifouling capabilities, which provides a new approach for the efficient industrial preparation of drug and macromolecular crystallization.

Key words: organic membrane, antisolvent crystallization, mass transfer, process intensification, liquid film renewal