An Extended Duration Operation for Porous Hollow Fiber-Based Antisolvent Crystallization

Poor aqueous solubility of numerous active pharmaceutical ingredients has raised considerable concern about the bioavailability of drugs. A porous hollow fiber antisolvent crystallization (PHFAC) device was designed to continuously produce drug nanocrystals under ambient conditions. The drug solution pumped into the shell side of the module encountered jets of antisolvent deionized water from tiny pores on the hollow fiber walls inducing a high degree of supersaturation as well as crystallization of the obtained nanoparticles. To study the effect of duration of operation for the PHFAC module and the stability of the nanocrystal production, a larger-scale and a smaller-scale module were designed to compare the nanocrystals in a 60 min long experiment. The characterized results showed that the nanocrystals were stable in size and morphology, and the nanocrystals produced by the larger-scale module presented no difference from those of the small-scale module. Meanwhile, the drug nanoparticles remained unchanged for the 28 days during repeated production, indicating excellent stability. It appears possible that the experiment could be scaled up to bring the application to industrial practice.