Pervaporation-assisted crystallization of active pharmaceutical ingredients (APIs)

• Published in: Advanced membranes 2023, Vol.3, p.100069, Article 100069
• Main Authors: Schmitz, Claire, Hussain, Mohammed Noorul, Meers, Tom, Xie, Zongli, Zhu, Liping, Van Gerven, Tom, Yang, Xing
• Format: Article
• Language: English
• Subjects: Active pharmaceutical ingredient; Membrane-assisted crystallization; Ortho-aminobenzoic acid; Pervaporation; Polymorphism control
• ISSN: 2772-8234; 2772-8234
• DOI: 10.1016/j.advmem.2023.100069

Crystallization of active pharmaceutical ingredients is essential in pharmaceutical production. Pervaporation, a thermally-driven membrane process, has not been explored in API crystallization. Here we demonstrated PV-assisted crystallization (PVaC) for simultaneous recovery of API ortho-aminobenzoic acid (o-ABA) and pure solvent. The PERVAP 4060 made of organophilic polymer was found suitable given the reasonable flux of ethanol of 3.69 ​kg/m2/h at 45 ​°C with saturated solution and 99.9% o-ABA rejection. A parametric study showed that the membrane permeance increased with feed flow rate and temperature, but decreased with supersaturation. In the sequential PVaC, the stable form I of o-ABA was obtained with 25 ​°C PV; while with 45 ​°C PV, only metastable form II crystallized. In the simultaneous PVaC, at 0 time lag pure form II was produced; by increasing time lag, form I increased significantly. The results indicated potential routes to control polymorph formation via PVaC, providing a promising alternative for API production. [Display omitted]