Continuous And Controllable Production Of Drug Nanoparticles By Novel Porous Hollow Fiber Anti-solvent Crystallizer

Nanotechnology can be used to develop nano drug delivery systems for improving the poor water solubility of Active Pharmaceutical Ingredient so as to enhance its vivo absorption rate and bioavailability.Meanwhile,in a variety of preparation methods,continuous crystallization methods have also attracted considerable interest of researchers due to its relative simplicity and practicability.In this paper,a novel porous hollow fiber anti-solvent crystallizer(PHFAC)based method has been designed to continuously produce nanocrystals of Griseofulvin(GF).In the PHFAC device,deionized water as the anti-solvent,was introduced to the shell side from the membrane pore,and acetone containing dissolved GF was introduced directly to the shell side of the device as the good solvent of drug.Water as the anti-solvent mixed vigorously with the drug solution contributing to a high level of supersaturation,which led to drug crystallization.The drug crystals were separated by vacuum filtration and freeze-drying.The particle size,size distribution and morphology of nanoparticles could be precisely controlled by varying the experimental conditions.The properties of drusg nanocrystals were characterized by transmission electron microscopy(TEM),scanning electron microscopy(SEM),dynamic light scattering(DLS),Raman spectroscopy,energy dispersive X-ray spectroscopy(EDX),differential scanning calorimetry(DSC),Fourier transform infrared spectroscopy(FT-IR),and X-ray diffraction(XRD)after experiments.Drug nanocrystals with sizes as small as 86.4 nm were successfully prepared in a continuous and controllable manner at ambient temperature and pressure.The results of dissolution test show that the dissolution rate of the drug nanocrystals(86.4 nm)was 54.0%in phosphate buffer in 130 minutes,while that of the as-received drug(3-4?m)was only 12.4%.In order to farther study the stability and maturity of the PHFAC device in industrial applications,a small-scale device and a larger-scale device were designed to compare the nanocrystals produced in 60 minutes in the experiments.The results indicate that the size and morphology of nanocrystals were stable and there was no significant difference between the nanocrystals prepared by the]arger-scale device and those prepared by the small-scale device.At the same time,the size of drug nanoparticles remained unchanged within 28 days,which indicated their good stability.This experiment lays a theoretical and experimental foundation for industrial practice on a larger scale.