Nucleation
is the initial step of the crystallization process and
is the significant step to prepare nanometer-sized crystalline materials.
In this work, we systematically investigated the nucleation kinetics
of poorly water-soluble drug sorafenib when precipitated by liquid
antisolvent precipitation in high-gravity rotating packed bed. We
found that high-gravity field tremendously promoted the nucleation
rate, and the nucleation rate was increased by 2–3 orders of
magnitude over that in the stirred tank reactor. Moreover, polymer
excipients have a significant impact on nucleation; especially, poly(vinylpyrrolidone)
(PVP) could increase the nucleation rate by 3 orders of magnitude
over that without excipient. Finally, stable amorphous sorafenib nanoparticulate
formulation with a particle size of 80 nm was obtained by controlling
nucleation in RPB. Compared to the coarse drug, the nanoparticulate
formulation performed faster drug release and had much better cytotoxicity.
In vivo pharmacokinetics of the nanoparticulate formulation displayed
the increase in plasma concentration time curve (AUC0–∞) and maximum plasma concentration (C
max), which demonstrated nanoparticulate formulation could enhance the
bioavailability and exhibit extensive potential in the pharmaceutical
industry.